Most of this is kind of complicated . . .

But one piece is real simple. BMJ only makes its full research reports open access, when it probably should be the social and political analysis and commentary that's available to the public. This time, however, it works out with this report from RD Smyth and colleagues, PR Williamson senior author, Liverpudlians all.

To try to put this in a pistachio shell, they tracked down investigators whose published clinical trials seemed not to report all of the results they had obtained or specified in the trial protocol. We all know about publication bias -- negative findings (in this context meaning, the medication didn't work) tend not to get published, partly because of drug company perfidy and partly because of the biases of journal reviewers and editors. But these folks wanted to find out from the horse's mouth (where does that expression come from, anyway?) why these investigators only published some of what they found, or didn't publish on their protocol outcomes.

I will digress to remind readers that it is very important to a) report your pre-specified outcomes and b) report negative findings. Not doing so can bias the overall weight of evidence. Pre-specified outcomes are important because those represent true hypothesis tests. Therefore the associated p values are technically valid and the evidence is strong. Reporting on findings you weren't originally looking for can result in spurious observations being accepted as convincing evidence. Negative findings are important because bias toward positive findings obviously makes interventions look better than they really are. And even more obviously, evidence of harm must be revealed.

There was a very high refusal rate for this study, and you can reasonably presume that people were more likely to refuse when they thought they had something to hide. Also, industry funding was associated with frequent claims that trial protocols were confidential. So we can bet that the situation is worse than what the Liverpudlians could uncover.

Mostly, respondents said things like, they thought that negative and non-significant findings just weren't interesting; the word limits for journal articles made it hard to talk about everything; they just didn't think one or another result was important; or it turned out they couldn't bring in the sample size they needed within their budget. Somewhat shockingly, about half of protocols -- which managed to get funding and ethical approval -- did not have specified primary outcomes. Hmm. I'd like the contact info for those funders.

So this is not good news. For those who are suspicious of how evidence based evidence based medicine really is, your antennae should be tingling because it looks like a lot of investigators aren't being trained properly and don't understand what they need to be doing. But there is also this quote:

When we looked at that data, it actually showed an increase in harm amongst those who got the active treatment, and we ditched it because we weren’t expecting it and we were concerned that the presentation of these data would have an impact on people’s understanding of the study findings. It wasn’t a large increase but it was an increase. I did present the findings on harm at two scientific meetings, with lots of caveats, and we discussed could there be something harmful about this intervention, but the overwhelming feedback that we got from people was that there was very unlikely to be anything harmful about this intervention, and it was on that basis that we didn’t present those findings. The feedback from people was, look, we don’t, there doesn’t appear to be a kind of framework or a mechanism for understanding this association and therefore you know people didn’t have faith that this was a valid finding, a valid association, essentially it might be a chance finding. I was kind of keen to present it, but as a group we took the decision not to put it in the paper. The argument was, look, this intervention appears to help people, but if the paper says it may increase harm, that will, it will, be understood differently by, you know, service providers. So we buried it. I think if I was a member of the public I would be saying ‘what you are promoting this intervention you thought it might harm people—why aren’t you telling people that?

Res ipsa loquitur. And I'd sure like to know what that shit is so I can make sure not to take it.

Stuck in the woods

I'm snowed in today, which you would think might lead to a super special blog post, but I don't seem to be up for it. I will, however, cast the blame for my situation.

The National Climate Data Center has released its report on the global climate in 2010. Break out the champagne, folks, we just tied the record. 2010 was the warmest year the planet has experienced since useful records have been available -- that would be 1880. It's actually a tie with 2005, but hot enough.

Oh yeah -- it was also the wettest, although the wetness was spread around very unevenly. So we had an unusual number of extreme weather events. A warmer atmosphere holds more water vapor, so you get more rain and snow. You also get unusual configurations of the jet stream and other weather patterns, so some places get droughts even while others are getting flooded.

This is for real folks. It's happening now, you don't have to wait until 2030. By the way arctic North America is extraordinarily warm right now, and most of Hudson Bay is ice free. That's really weird. And according to an increasingly popular hypothesis, it drives more cold arctic air south. So there's no paradox here. (Actually it hasn't been all that cold for January in New England anyway.)

How we can get people to focus on this, in the face of a very well-funded denialist campaign and a Fair and Balanced media, I don't know. But I do feel I need to do my own tiny part here, and I will.

Relative wrongs

It's a big deal when somebody intentionally and directly generates kinetic energy that injures and kills lots of people -- sometimes. Military personnel obviously have a license to do it under approved circumstances. You would think that lying to the world in order to start a war would be considered a monstrous moral offense, but apparently not if you happen to be the president of the United States. But at least some people remain outraged by that and there has been a bit of public discussion about it. We decided to look forward, not back, however, so there will never be a formal accounting.

But what about people who market tobacco, or unhealthy foods? It is estimated that tobacco addiction kills 5 1/2 million people around the world annually, an average of 15 years before their life expectancy without the disease. Well, here's a controversy almost nobody has heard of. You have probably heard of Carlos Slim, the wealthiest Mexican and a well-known philanthropist. It turns out that the main source of his wealth is tobacco. I'm afraid this Lancet article is subscription only, so I'll summarize.

Slim contributes as much as $5 billion a year to his foundation, Instituto Carlos Slim de la Salud, which supports public health programs in Latin America. Last year, he announced a joint contribution with Bill Gates to a project to promote child health in Central America. It turns out that Slim was for many years majority owner of the Mexican tobacco company Cigatam. He has since sold a majority stake to Philip Morris, on whose board he now sits. He acknowledges that the enormous cash flow generated by Cigatam was the key to building his conglomerate empire.

The Gates Foundation has previously withdrawn cooperation from a Canadian charity whose director turned out to have tobacco industry ties, so Simon Chapman asks why Gates is willing to work with Slim. But I have a deeper question. Why is this man considered respectable in any way? He is a mass murderer on a scale that makes Pol Pot look like a petty criminal.

We have an astonishing capacity for selective attention.

"A deranged killer"

For reasons which should be obvious, I did a little research into the association of schizophrenia with violence. This review article offers a good, clear discussion of the issues.

Although various numbers are bandied about for the degree of risk of violent behavior associated with schizophrenia, they should all be viewed with a degree of skepticism. There are several reasons why it is difficult to put a firm number on this association:

1. Schizophrenia is not a definite entity. There is no "gold standard" diagnostic test, it's based on clinical judgment. In research settings, it's often based on something short of adequate clinical judgment, such as a single encounter with a clinician. And the term undoubtedly encompasses more than one disease. The etiology of schizophrenia is unknown, and its associated biology very poorly understood.
2. All this means there are big problems with ascertainment bias. Maybe people who commit violent acts are more likely to be diagnosed with schizophrenia, because they come to the attention of potential diagnosticians; or because their behavior itself predisposes to a diagnosis.
3. On the other hand, selection bias probably works in the opposite direction. People with major mental disorders who are violent are less likely to agree to participate in studies, more likely to drop out, and harder to follow and recruit.
4. Studies based on people who have been convicted of violent crimes may understate the prevalence of schizophrenia because people with mental illnesses are often diverted from the criminal justice system. Also, schizophrenia could affect one's likelihood of being caught and convicted. One would think it would make it higher since the ability to plan and act rationally is impaired.
5. Ascertaining violent behavior is just difficult. Reliance on self-reports could obviously bias conclusions either way.

Still, triangulating on this question from many directions -- trying to ascertain the likelihood of violent behavior in people diagnosed with schizophrenia; trying to ascertain the prevalence of schizophrenia in people who have committed violence; and cross-sectional or even better, prospective cohort studies of community populations -- it appears that the risk of committing violence is higher among people with schizophrenia. It's still a a minority of all people with the diagnosis, but it appears that the risk of committing homicide is somewhere around 8 to 10 times that of people without diagnosed mental illness. Substance abuse disorders also predispose to violence, and definitely create a strong additive risk in people with schizophrenia. It has been said that conduct disorders are also strongly associated with risk but that's obviously circular since violent behavior is a diagnostic criterion for conduct disorder. Keep in mind, however, that people who are diagnosable with schizophrenia commit a small percentage of all violent acts, and that the vast majority of people with schizophrenia are not violent. We need to be honest about this problem without promoting stigma or discrimination.

As far as politically motivated, or apparently politically motivated violence is concerned, there are a couple of famous cases that are relevant. John Salvi, who went on a murderous rampage at two abortion clinics near my home, was indeed a devout Catholic who attended anti-abortion protests and associated with anti-abortion activists. He was also without a doubt psychotic. He ultimately took his own life in prison after receiving a life sentence. Ted Kaczynski was diagnosed with schizophrenia by a court appointed psychiatrist, but I find this highly questionable. He clearly has impairments in social skills and empathy, and he's a weird guy, but his thinking is neither delusional nor disordered as far as I can tell. (I don't condone long distance diagnosis and I'm not a psychiatrist, but I just don't think he meets the criteria for schizophrenia so there.) Both of these individuals did indeed subscribe to coherent political ideologies, which were broadly similar to ideas promoted by movements and organizations, although Kaczynski appeared to believe that his thinking was highly original.

But it's a pretty big stretch to say that those ideologies and their champions are to blame for these people's actions. Other anti-abortion terrorists clearly were acting with intent based on the logic of their ideology, but Salvi actually believed that he would be ordained as a priest after committing his crime. And I know of no other deep ecology proponents who mail bombs. Earth First! and similar organizations attack property, but not people. We've heard a lot of nonsense of all descriptions about the tragic events in Tucson, but here's what I think. The guy is completely nuts. Yes, the violent and eliminationist rhetoric coming from the extreme right -- which is the center of the Republican Party -- is atrocious and must stop. But it's a real leap to say it had something to do with this incident.

Update: To clarify, I'm not saying it didn't. I'm just saying we don't know yet. And it is certainly true that all the violent rhetoric that's out there is dangerous in part because it can influence delusional systems such as John Salvi's. I'm just trying to carefully sort these matters out, that's all.

Fraud

Scientific fraud is not terribly rare in one sense. Just about every month NIH publishes official Findings of Scientific Misconduct. But these are almost always a post-doc or a junior faculty member who faked a slide in a proposal or something on that level. I'm sure a lot of fudged data finds its way into the literature, and I know for sure that quite a bit of data mining goes on.

For the uninitiated, that's when you look around in a data set for significant associations, and then pretend you hypothesized them when actually, you just stumbled on them. That's bad because it means your tests of statistical significance are invalid and your findings may well be spurious. It's one of the big reasons why a lot of findings don't hold up actually, because they weren't really legit in the first place.

What you're supposed to do when you come across an unexpected association is treat it as a hypothesis and then try to confirm it with fresh data. But the reason why people don't always do that is the same reason the post-doc faked the slides and data gets fudged -- there's tremendous pressure to publish and get funding, and if you don't, you are likely to get squeezed out of academia entirely and you're selling insurance or something. At best your grand ambitions go unfulfilled and you're working as a drudge in somebody else's lab or teaching as an adjunct for a few thousand bucks a course until you've finally had enough. So the temptations are strong.

But the vast majority of fraudulent or questionable publications are basically inconsequential. They don't lead anywhere, and the worst that happens is that better work gets crowded out of the journal and possibly some other investigators gets sent briefly down a blind alley. What is actually rare is a consequential fraud like Andrew Wakefield's that convinces a lot of people of something that isn't true and is actually important. Even Marc Hauser, if he did indeed commit fraud rather than succumb to wishful thinking (a distinction without a difference, I think, since appropriate methods would have precluded the latter), didn't do much substantive harm. The cognitive abilities of macaques are not a matter of life and death.

But for someone to perpetrate a fraud as consequential as Wakefield's takes a very special kind of personality. He wasn't just fudging some numbers to win a grant or get a paper published in an obscure journal on an arcane subject. He went right to the heart of medical practice and attacked what has been, without question, the single greatest boon to humanity ever delivered by biomedicine. (I'll assign clean drinking water and sanitary child birth to public health, since they aren't medical interventions but rather harm avoidance based on understanding of pathogens.)

The only reason an anti-vaccination movement can exist is that vaccination has been so successful. If kids were dying of smallpox and polio and measles today, believe me, Jenny McCarthy would be screaming and yelling to make sure every kid got every shot. People today just have no idea of what human existence was like before the development of modern vaccines. Life was cheap. People didn't expect most of their children to become adults, they just hoped for it. If you didn't die, you might be disfigured by smallpox or paralyzed by polio or sterilized by mumps. Women who had rubella during pregnancy had profoundly retarded infants, who filled institutions. That's how it was.

If Andrew Wakefield had his way, that's how it would be today. And why did he do it? The way I read Brian Deer's story, he did it for money.

Not much I can add to this . . .

Orac and the gang are all over it of course. Pit bull reporter Brian Deer, who has had his jaws clamped onto psychopathic mass murderer Andrew Wakefield for years, finally drags his quarry to the ground. He demonstrates what we have all always suspected -- Wakefield's study suggesting a link between the MMR vaccine and autism wasn't just sloppy and wrong, it was intentionally fraudulent. Whether Her Majesty can find a way to prosecute him remains to be seen, but it will be a shame indeed if he gets away with it.

I'll bet you can predict how the corporate media are covering this. Yep, they're Fair and Balanced. Here's CNN's headline and lede:

Doctor Defends Retracted Autism Study

A physician accused of an "elaborate fraud" in a now-retracted British study that linked autism to childhood vaccines is defending himself, telling CNN his work has been "grossly distorted."

Speaking on CNN's "Anderson Cooper 360," Dr. Andrew Wakefield said Wednesday he has been the target of "a ruthless, pragmatic attempt to crush any attempt to investigate valid vaccine safety concerns."

The story then briefly summarizes the accompanying editorial in BMJ, gives Wakefield another shot: "Wakefield dismissed Brian Deer, the writer of the British Medical Journal articles, as "a hit man who has been brought in to take me down" by pharmaceutical interests. Deer has signed a disclosure form stating that he has no financial interest in the business," gives Deer a chance to deny that he is a tool of the pharmaceutical industry, then brings in Wakefield's fans to pile on more horse manure:

Wendy Fournier, president of the National Autism Association, defended Wakefield in a CNN interview.

"I cannot imagine for a second that Dr. Wakefield would have any reason to falsify data," she said. "He's a man of integrity and honesty and truly wants to find the answers for millions of children who have been affected by autism."

Fournier accused pharmaceutical companies of trying to protect their turf.

"You can't question vaccines without being destroyed," she said. "There's too much money at stake here."

J.B. Handley, the father of an 8-year-old with autism and a co-founder of Generation Rescue -- a group that believes there's a connection between autism and vaccinations -- also questioned the motivation behind the investigation into Wakefield's work.

"Children are given 36 vaccines in the U.S. by the time they reach the age of five," he said. "This is an attempt to whitewash, once and for all, the notion that vaccines cause autism."

There's is some more He Said/She Said and then Wakefield's defenders get the last word:

Wakefield's defenders include David Kirby, a journalist who has written extensively on autism. He told CNN that Wakefield not only has denied falsifying data, he has said he had no way to do so. "I have known him for a number of years. He does not strike me as a charlatan or a liar," Kirby said. If the BMJ allegations are true, then Wakefield "did a terrible thing" -- but he added, "I personally find it hard to believe that he did that."

Of course Wakefield had a way to falsify his data -- just make it up. And that's what he did.

So that's it -- your typical "Shape of the Earth, Views Differ" story. This matter is settled. It is not controversial, it is not a debate on which reasonable people can differ, in which both points of view must be given equal consideration. On one side you have people who are stating facts, and on the other hand you have liars and their victims. Yet the corporate media seems incapable of grasping the situation.

If they can send a man to the moon . . .

Actually I've used that title before. Anyway, they're still working on the urgent public health problem of baldness, this time in the general realm of regenerative medicine. That's all about how newts can grow new limbs and hearts, so why can't mammals? Basically, we don't have the progenitor cells needed to regenerate tissue, and in the case of people afflicted as I am, that happens to be hair, which is not exactly tissue but it's a similar idea.

Obviously, baldness isn't actually a health problem.

I take that back. If "health" means a state of well-being, then it is whatever makes you think you are well. But if bald men feel unwell, it's because of their worries about how others see them. This same problem comes up with short stature -- which has become a disease now that hormones are available to make children grow taller -- and homosexuality, which used to be a disease but is no longer, because social attitudes have changed. Originally, as a matter of fact, calling homosexuality a disease was seen as a step forward for homosexuals, because it's better to have a disease than a moral failing. In Leviticus, baldness may or may not be a moral failing depending on specific criteria. Simple male pattern baldness seems to be exempted, but if the priest were to make a misdiagnosis, a bald man could end up driven into the desert to die:

40 “A man who has lost his hair and is bald is clean. 41 If he has lost his hair from the front of his scalp and has a bald forehead, he is clean. 42 But if he has a reddish-white sore on his bald head or forehead, it is a defiling disease breaking out on his head or forehead. 43 The priest is to examine him, and if the swollen sore on his head or forehead is reddish-white like a defiling skin disease, 44 the man is diseased and is unclean. The priest shall pronounce him unclean because of the sore on his head.

All this is banal, but there is a deeper point. Our well being is partly a function of how our physical and behavioral characteristics are regarded by others. It is socially as well as biologically determined. Exactly how unhealthy a person is who has, say, difficulty walking, or who stutters, or has a benign but visible tumor, or a so-called paraphilia, is determined by the rest of us and the environment we create. We could create a lot more health by investing in cultural change, in many instances, than in biomedicine, even before we get to the problems of social class and material resources.

The Straight Dope

You may have come across this dispute in New York City over graphic HIV prevention advertisements. The city health department is concerned that young gay men are thinking that HIV isn't so bad after all, just take a pill and you'll be fine. So they're using scare tactics, with graphic images of anal cancer and warnings of dementia and dissolving bones.

Lots of people are unhappy with the ads, on various grounds. Jarrett Barrios, an acquaintance of mine who was once a Massachusetts state senator and now head of the Gay and Lesbian Alliance Against Defamation, says they just aren't accurate -- living with HIV isn't really all that bad. Others fear the ads are stigmatizing, of both gay men and people with HIV.

Others support them however, because they really, really want young gay men to stop getting infected with HIV. On the other hand, it isn't at all clear that such scare tactics really work in changing people's behavior. The latter point is obviously a very strong one. The downsides are only acceptable if the ads have a big effect in HIV prevention. Unfortunately nobody can say for certain. The common wisdom is that in most contexts, trying to scare people into not doing stuff they otherwise want to do isn't very effective.

The American Legacy Foundation youth tobacco prevention ads, which the article asserts were comparable, were not comparable at all. Rather than trying to scare people into not smoking, they (truthfully) portrayed tobacco as a product pushed by old, greedy fat cats and hence decidedly uncool; while way cool rebellious and hot looking young people hit the fogeys with anarchistic direct actions.

I can't exactly think of a comparable tactic to use against HIV, and I wouldn't want to make the drug companies a target although it is true that they're advertising in gay-oriented literature does make it seem as though living with HIV is not a prob. They shouldn't do that. But I will tell you what it's really like to live with HIV.

It is true that if you are diagnosed in time, before you lose too many T-cells; and you get access to good medical treatment, which you have insurance or other means to pay for, you will have the opportunity to remain reasonably healthy for a long time. That is if and only if you take medications consistently, for as long as you live. You may be unlucky and have unpleasant or even intolerable side effects from the first regimens you try, although most people don't.

But over time, long term side effects are common, including disorders of lipid metabolism which can include disfiguring redistribution of fat deposits; high cholesterol; diabetes; and weight gain. Painful peripheral neuropathy is also encountered with some medications. If you don't take the pills consistently, you may develop viral drug resistance and have to switch to more complicated, less well tolerated regimens. And in spite of effective treatment, it does appear that HIV can continue to slowly damage the brain and lead to early onset dementia. You might be lucky enough to escape the worst of these consequences, but don't bet on it. Chances are your life will be shortened.

I don't want to exaggerate any of this. Lots of people with HIV do very well for decades. Your lot today will be much better than it was before there were effective treatments - these side effects beat the hell out of uncontrolled HIV disease and AIDS. But believe me, this is something you would much rather live without.

Yes,the ads are inaccurate because the dire consequences they portray aren't going to happen while you're still young, and the anal cancer thing is a bit of a red herring since that is caused by a different virus, although it's still a good reason to always use condoms so I can forgive it. I would rather see messages that are unassailably accurate and are more about positive motivation than negativity and fear. I think the health department could have done a lot better.

But I can also understand why some people are getting frustrated enough to try anything. Nobody has to get HIV from voluntary activity. And you really, really don't want to. So don't.

The big public health story of 2011

As Yogi said, I believe, or at least he said something like this, it's hard to make predictions, especially about the future. But I am pretty sure that in 2011, people are going to be talking about the weather even more than usual.

Everybody has heard of the flooding in Australia, where half of Queensland is under water. I pay pretty close attention to the news, but I only noticed recently that Colombia is in even worse shape. Mozambique got hammered last spring, and of course you've heard about Pakistan although it fell off the corporate media radar pretty quickly. Unprecedented flooding in the U.S. in Nashville and the Rio Grande area, and now in Southern California, also made the news last year. New Year's day tornadoes in the midwest? That too.

A warmer earth means a more energetic atmosphere, that holds more water vapor. We don't have to wait until 2050 to see the result, it's happening now. In the U.S., where we generally have adequate warning of these events, and people have means to evacuate, we don't often have large numbers of deaths, at least not as an immediate, direct result of flooding. But when people are displaced, communities destroyed, homes and livelihoods lost, the consequences can be severe in the long term.

Insurance companies are convinced, even if Republicans are not. So are the leaders of China, and the U.S. military. I've given a couple of links to Climate Progress already, and I recommend that you bookmark it. This is for real, folks. And it's coming faster and harder than just about anybody predicted even two years ago.

Apo-calypso

I believe we're supposed to look back and look forward today, but instead I'm going to look at those people who look forward a certain distance and see a blank wall, at least in ethical terms.

I don't know if it's peculiar to the U.S., particularly, but we certainly are well endowed with eschatological movements. Eschatology and "end times" don't have to mean the end of time -- the dictionary says the terms can also refer to beliefs about radical transition from one age to another. Obviously such transitions have happened, whether we're talking about the universe, the planet, or humanity. We Homo sapiens are undoubtedly in one right now, and we're dragging the planet along with us.

But I'm talking about believers in change so radical that we owe no obligation to the future. Christian millenialists generally fit this definition. God is going to end history, Jesus and the Beast are going to battle it out, supernatural forces will bring about a future which, according to various interpretations, may or may not include the earth in some form but in any case, what we do to it today doesn't matter. Believing in the right mumbo jumbo might influence our personal fate, but that's all we have to worry about. Ronald Reagan's Secretary of the Interior, James G. Watt, was of this opinion, and used it to justify unrestrained exploitation of natural resources. What did it matter? The world would end soon anyway.

But it takes many other forms. I remember back in college a guy telling me I was foolish to worry about what to do with my life because the planets were going to align on March 10, 1982 and wipe out civilization. A couple of wacko charlatans named Mark L. Prophet and Elizabeth Clare Prophet told their followers in the Church Universal and Triumphant that World War III would occur on April 23, 1990. The people disposed of their possessions and moved to the Church's ranch in the Grand Tetons to wait it out in fallout shelters. You won't be surprised to learn that the CUT (weird acronym, huh?) has sailed on just fine ever since, despite the perfectly ordinary day that passed.

Then of course civilization was going to end on January 1, 2000, either because of Jesus or because the computers would all freak out. As it turned out, the state of Maine erroneously issued some antique license plates. We could go on but much of this is familiar.

What inspires me to write today, however, is a conversation I recently had with a friend that I found a bit disconcerting. He's a pretty well-known writer and he's very insightful. His new idea is that predictions of global climate change are a modern form of eschatology, and he very much wanted me to concede that we are living in the end times. I must say that I find that locution inaccurate, and unhelpful as metaphor.

I agree that it is too late to prevent profound change, and that times of great strife and woe lie ahead. However, we are not running up against a blank wall. The perils we face do not mean that there is just nothing on the other side. That would abolish all responsibility, which as I said at the top (tell 'em what you're gonna say, say it, tell 'em what you said) is characteristic of what we generally mean by eschatological thought. The crisis we face is very different from end times prophecies in many ways.

First of all, it is protracted and gradual. My friend agrees with that. Just as important, and I'm not sure everyone who should be is on board with this, it is highly uncertain. Many people make all sorts of exact predictions but in fact we can only speak in terms of probabilities of various direct effects on the climate system and indirect effects on humanity and the ecology. We don't really know exactly how matters will play out meteorologically, oceanographically, ecologically, demographically, or socially.

Most important of all, we do not face the end of civilization or the extermination of humanity. I can see no remotely probable scenario in which our species disappears in the foreseeable future. We are just too adaptable. What's going to happen is that the weather is going to change, some coastal areas will be inundated, and biological productivity may become somewhat less. Some number of people will figure out ways to keep going.

That will likely mean fewer of us, and a different way of life, but that has happened before. Europe not only survived the Black Death, but emerged into a great flowering of science and culture. One key difference today is that those of us who are willing to see have a basic understanding of what is happening and can plan and act to protect the future as best we can. The planet will still be here and so will its currently cancerous Homo sapiens. With luck our uncontrolled replication and rapacious metastasis will be cured, and we can carry on with the next age of history.

That's hard times, but it's not the end times.

The Visionary

Salviati: ... it is necessary that we declare ourselves as to whether or not you and I have the same concept of this center. Therefore tell me what and where this center is and what you mean.

Simplicio: I mean by "center" that of the universe, of the world; that of the stellar sphere, that of the heavens.

Salviati: I might reasonably dispute whether there is in nature such a center, seeing that neither you nor anyone else has so far proved whether the universe is finite and has a shape, or whether it is infinite and unbounded.

(From the third day of the Dialogue)

Galileo's project, ultimately, was not merely to demonstrate that the earth goes around the sun. That was just one instance of a much larger vision, which was fundamentally epistemological. By throwing off the shackles of received wisdom, and setting out to discover the universe as it revealed itself, he freed his imagination to conceive of a universe far grander and more wonderful than the church fathers could encompass. In this respect, it was in fact the one we know today -- unbounded and with no center. His telescope could not resolve the nebulae into galaxies, but he had an idea that the stars were suns, and the sun a star.

It is astonishing that nearly 400 years later, the implications of this insight are still so threatening to most Americans that they do not accept it. We are, after all, nothing special. We are not the principal interest of the almighty lord of creation, and the fate of our planet is of no consequence to the universe. It matters only to us and to the creatures with which we share it. If we could just abandon the delusions of religion, we might have a better shot at not screwing it up.

Priorities -- and this time it's personal

Mark Fischetti in Scientific American provides a picture of federal spending on scientific research and development. In 2009, the Department of Health and Human Services got about $29 billion. The Department of Defense got $56 billion. Other money is scattered here and there, some of it for social benefit, such as $343 million for the Department of Education (that's with an M, not a B, in other words less than 1/100th of what DoD gets), and $3.6 billion (back to a B again) for the National Nuclear Security Administration.

Republicans are vowing to cut all non-defense research spending, as you may have heard. They can do it, too, because appropriations require affirmative action by the House of Representatives. The Senate and President can't do anything to produce appropriations the House doesn't generate.

My work is funded mostly funded by NIH, the biggest component of HHS R&D spending at $28.5 billion. I'm dependent on a very small part of that, however. The U.S. supported only about $1.1 billion in social science research in 2009. Right now, many investigators are waiting on grants that haven't come through because the federal government is operating on a continuing resolution that level funds all the agencies, and the NIH institutes and centers are reluctant to commit to new projects since they don't know what's going to happen in March when it runs out.

We'll all keep trying, of course. NIH isn't going to go away. But the current level of funding has created a community of investigators of a certain size. If it falls, some number of post-docs will never get faculty appointments and some number of research faculty will get squeezed out. The pace of discovery and translation to better medical care will slow down. The hope you may have for better treatment or prevention for MS or Alzheimer's or pancreatic cancer or HIV will be delayed; the work I do to improve the delivery and effectiveness of medical services will slow down too, in case anyone cares.

On the other hand, we will, if the Republicans have their way, continue to invest more and more in better and more effective ways to kill and maim people. It is, after all, the Christian thing to do.

Mobility

I didn't post yesterday because I had to deal with snow removal in two places, with a substantial travel ordeal in between -- including following a rolling roadblock of snowplows down the interstate at 20 miles an hour. Whenever we have a big weather event like this, it makes me think about the curses and the blessings of modernity.

The big news -- which is still dominating all the networks 24 hours after the storm pulled away -- is all the unfortunates stuck in airports. That is truly unpleasant. On the other hand, air travel wasn't a routine habit of the ordinarily affluent until 50 years ago, at the most. Either you stayed close to Waga Waga where you grew up, or you just said goodbye to your parents and sent them Christmas cards. If you did go to see them once every few years, it took several days anyway.

Streetcars made suburbs possible, but they were a different kind of suburbs than the ones we know today, spawned by the automobile. Streetcar suburbs -- which to a large extent have been incorporated into their parent cities -- were organized around town centers where the people could walk to stores and church and taverns. Automobile suburbs are monocultures of houses on landscaped quarter acres from which people drive to shopping centers and soccer practice.

There are environmental consequences, which are obvious, but the social consequences are just as profound although we think about them less. Most of the friends I have made in the course of my life are hundreds or thousands of miles away. That's basically normal. Growing old nowadays often means becoming alone, but lots of younger people are pretty isolated as well.

When we adopt new technologies we are entirely short-sighted. We see what they do for us immediately, but have little thought of how they will change the fabric of life. Truly, we probably could not predict that anyway.

Many people think and write about these issues but they aren't much a part of popular consciousness or political discourse. We have a bedrock assumption that innovation equals progress. On balance, perhaps, it seems true to most people so far. Deaths in automobile crashes are more than balanced out by children not dying of infectious diseases. Routine tourism to exotic lands is fun, although perhaps not as enlightening in most cases as we would like to think. Global trade fills our world with stuff, even if it leaves a lot of workers behind. But it's worth thinking about the balance sheet much more carefully than we ordinarily do, and having more concern about how all these bargains will look in a few years.

Knowing

Simplicio: From the oldest records we have it that formerly, at the Straits of Gibraltar, Abila and Calpe were joined together with some lesser mountains which held the ocean in check; but these mountains being separated by some cause, the opening admitted the sea, which flooded in so as to form the Mediterranean. When we consider the immensity of this, and the difference in appearance which must have been made in the water and land seen from afar, there is no doubt that such a change could easily have been seen by anyone then on the moon.

(From the Dialogue Concerning the Two Chief World Systems)

By giving these words to Simplicio, Galileo clearly is not trying to argue for this conclusion. But as neither Salviati nor Sagredo object, it also seems that this opinion was generally held among the educated Venetians in 1632 and that Galileo either did not doubt it, or did not care to contest it.


What is most surprising is that geologists today believe this to be true. The event, called the Zanclean Deluge, happened more than 5.3 million years ago. Therefore it seems impossible that the people of Galileo's time could have known it based on any good evidence.

It seems to have been a lucky guess by Pliny the Elder, hence the principal relevance to our present interest. The Dialogue does not reference the Bible at all, and barely glances at religion. The debate is between the theoretical insights of Copernicus and empirical observations of Galileo, on the one hand; and the authorities of classical antiquity on the other. I'm sure that Galileo could not have directly challenged the Bible and expected to avoid being tortured to death. Nevertheless, while I am not an expert on his time, it does seem clear that Old Testament literalism was not the prevailing intellectual fashion, but rather fealty to Aristotle and the classical philosophers.

Indeed, Galileo had presumed he could convert the church authorities to his cosmology, and had actively sought them out to make his presentations. He was very unpleasantly surprised by the reaction he got. I'm sure the authority of the Bible was salient in his hearings before the Inquisition, but I do not think it was Biblical literalism the church was concerned to defend so much as the metaphysical implications for the relationship between God and humanity of moving the earth from the center of the universe.

And they were right to be afraid of this. Galileo, in fact, did not put the sun at the center of the universe either, as he states in one of the most astounding passages in the Dialogue, to be considered anon.

Quote of the Millenium

Salviati: In the long run my observations have convinced me that some men, reasoning preposterously, first establish some conclusion in their minds which, either because of its being their own or because of their having received it from some person who has their entire confidence, impresses them so deeply that one finds it impossible to get it out of their heads. Such arguments in support of their fixed idea as they hit upon themselves or hear set forth by others, no matter how simple and stupid these may be, gain their instant acceptance and applause. On the other hand, whatever is brought forward against it, however ingenious and conclusive, the receive with disdain or with hot rage -- if indeed it does not make them ill. Beside themselves with passion, some of them would not be backward even about scheming to suppress and silence their adversaries. I have had some experience of this myself.

Sagredo: I know; such men do not deduce their conclusions from its premises or establish it by reason, but they accommodate (I should have said discommode and distort) the premises and reasons to a conclusion which for them is already established and nailed down. . . .

-- Galileo Galilei, Dialogue Concerning the Two Chief World Systems, translated by Stillman Drake.

I will have a good deal more to say about this astonishing, and lately insufficiently appreciated document, in coming weeks. Salviati is Galileo's alter ego; Sagredo is his friend who stands for the open-minded interlocutor.

For more wonkery on the same subject . . .

I recommend William Pewen's blog at Health Affairs. Basic points, all true:

1) The individual mandate, in spite of the compelling practical arguments in its favor, does create potential problems when it interacts with legal sophistry. Justices could easily decide either way as to its constitutionality and construct sufficient arguments to not look ridiculous, but you and I both know that their ultimate motivations will be political. And hey, it's 5 to 4.

2) Without the mandate, the PPACA won't work. This is because of basic features of the market for health insurance, which by the way don't resemble anything they teach you in freshman economics. (Sorry to be a broken record on that one.) If insurers have to issue insurance to everybody, at more or less the same price, people who think they are unlikely to need it won't buy it, which will make it more expensive for people who are likely to need it, which will drive out the somewhat likely, making it even more expensive for the highly likely -- in other words, The Death Spiral, and the insurance market has been destroyed.

3) There was a much simpler and better way to do this all along: Medicare for everyone. Universal, comprehensive, single payer national health care. No constitutional problem whatsoever. Congress has unequivocal power to raise taxes to promote the general welfare. QED. The reason we didn't do this is because conservatives wanted to protect the private insurance industry, which was shoveling money at them. And now they are trying to get the very creature they birthed declared unconstitutional. And they might just succeed.

So let's say it again:

We need universal, comprehensive, single payer national health care.

Owned! (I think I was supposed to type Pwn3d or something)

I presume, although maybe I should not, that the New York Times tries to publish a representative sample of letters in response to any given news story or op-ed column. If that is correct, it appears that Jason Mazzone's recent argument that the health care reform act is unconstitutional did not, shall we say, persuade a high proportion of readers.

After the bill passed, as conservative state attorneys general began to file lawsuits, most knowledgeable commentators dismissed these as stunts intended to appease the inhabitants of wingnutistan and predicted that they had no prospect of advancing. They did not reckon with the judicial activism of the right, however, and I am now far from sanguine. Now that they have found a federal judge to agree that the law is unconstitutional, the case will inevitably make it to the Supreme Court no matter what, and the same justices who produced Bush v. Gore are sitting there licking their chops as they wait for it.

The basic argument, defended by Mazzone, is that the Commerce Clause does not give Congress the power to force people to engage in economic activity. As the letter writers point out, this is basically nonsensical. I can even make a few points of my own. Paying taxes is economic activity, and so is buying a stamp to mail your tax return. So is paying whatever the additional cost may be for all regulated goods and services. In order to carry out any public purpose, under the Commerce Clause, Congress reallocates costs and income in one way or another.

The fact is, if your appendix bursts, or you are shot using an unregulated hand gun, or you ride your motorcycle without a helmet and end up getting scraped off the asphalt, all of us will engage in economic activity by paying for your medical treatment. If making you buy health insurance, along with various measures to make sure you can afford it, is unconstitutional, so is requiring doctors and hospitals to treat people in emergencies. Which the federal government already does, and with good reason. Your supposed "liberty" not to buy health insurance infringes my liberty to hold onto my own money. Which is just one more reason why libertarianism is fundamentally nonsensical.

Yet somehow, utter nonsense dominates our political discourse.

A miracle

A conversation I had today got me thinking about the times I've lived through. I worked my way through graduate school doing consulting work for community based organizations. My friend Wayne Wright, who died of AIDS in 1995, was Executive Director of the Multicultural AIDS coalition, and he connected me with many community based AIDS service organizations, for which I did program planning, proposal writing, strategic planning and other work.

Wayne had really bad luck. Effective treatment for HIV became available just after he died, with the approval of indinavir in 1996. Up until then all we seemed to do was death watches and memorial services. If you weren't in a big city and didn't have any relationship with heavily affected communities it was just something happening to other people, and specifically other people who you probably didn't like very much. (That's "you" in the generic sense, not referring to my own readers.) I'm not gay but there I was in the middle of it, one friend or respected colleague after another, young men mostly, energetic and passionate and committed to good works dying horrifically. It wasn't just the individual losses that kept piling up, it was the devastated communities, whole swaths of life smashed and the pieces scattered to the winds.

This must be what it is like to be in the midst of war. I'm sure great disasters like Hurricane Katrina or the southeast Asian Tsunami felt similar. But for most of us, such plagues belong to history. They're just stories in books we haven't read.

And then the miracle happened. One of the most important AIDS-related institutions in Boston was the Hospice at Mission Hill, where the lucky went to die. In 1996, they started rising from their death beds, emaciated bodies filling out with muscle and fat, people who had figured out how to die suddenly having to figure out once again how to live. The latter problem was sometimes harder. Nowadays the biggest challenges people with HIV usually have are the challenges of growing older, living with a burden to be sure but not necessarily a very large one. It was astonishing. I do not have words for this event.

And so there must be special circle deep in hell reserved for the lunatics who continue to deny that HIV causes AIDS and that antiretroviral drugs keep people with HIV healthy. Some of them, such as Mathias Rath, are psychopaths whose evident motive is greed. Others, such as Peter Duesberg, are evidently afflicted with profound psychological problems. You can read about a whole bunch of them here. Sadly, they still manage to convince people not to take the pills, and the result is that those horrible deaths still happen when they really don't have to.

Now, people in Africa still can't get access to treatment, and we're falling farther and farther behind. More people are infected each year than are enrolled in treatment programs. And that's even starting to happen in the U.S., where the states are broke and are putting people on waiting lists for antiretrovirals -- including right here in Rhode Island, which isn't exactly Mississippi. In the richest country in history, we're telling people to go drop dead. Hey, at least the rich people don't have to pay two percent more in taxes on the portion of their income they can't shelter completely.

A brief primer on drug regulation wonkery

I realize there is a lot of potential for confusion when we talk about the drug approval process and exactly how consumer protection and drug company economic interests interact. I'm not actually a major expert on these issues myself but I think I can at least give you a handle on some basic concepts that will help clarify matters.

First, drug manufacturers, like every enterprise engaged in research and development, can file for patents on new compounds. These generally last for 20 years. As long as a company holds a patent on a compound, no other company can sell it, unless they come to an agreement with the patent holder and (ordinarily) pay royalties.

However, you can't legally sell a drug and make health claims for it without FDA approval -- called a drug license. (Not to be confused with a license sold by a patent holder to another company to make the drug.) Before getting a license to market a drug, a company first gets an investigational license that allows them to test it in clinical trials. By the time this process is completed and a company is licensed to market a drug, much (if not all) of the 20 years of patent protection has expired. So Congress has sweetened the incentive to develop new drugs by also allowing the FDA to grant additional marketing exclusivity periods, typically of 5 years.

If a drug is licensed, then physicians can prescribe it (or it can be sold over the counter if it has that kind of license). However, the drug companies are additionally restricted by the FDA in the specific claims they can make when they market the drug. That won't necessarily stop doctors for prescribing it "off label," for unapproved indications, but the companies are not legally allowed to encourage them to do so. This is a major problem area. Enforcement has been lax, and drug companies have found all sorts of ways of getting around these restrictions.

Once both the patent and marketing exclusivity periods have expired, other companies can apply to manufacture the drug. But they have to satisfy the FDA that their formulations are biologically equivalent to the original. The original license holders can intervene and contest these claims.

Once generic versions of a drug are available, the price typically goes way down, because now there is competition. The unit cost of manufacturing a pharmaceutical is usually trivial. Drugs are expensive because of marketing exclusivity which allows manufacturers to charge whatever they think they can get.

The final layer in this casserole is insurance reimbursement policy. Medicare is pretty much required to pay for drugs prescribed for any approved indication, but private insurers can set their own policies and they often have tiered co-payment systems that encourage use of medications which are cheaper for them. They can also refuse to pay for certain treatments if they choose. This is an endless source of confusion to physicians who have to deal with patients whose insurers use different "formularies," or lists of approved drugs at various levels of copays.

Drug manufacturers try to extend their marketing exclusivity by coming up with just slightly different versions of old drugs that they hope they can persuade consumers and physicians are better and hence worth paying brand name prices for. This is called "evergreening." The whole COX-2 inhibitor fiasco can be understood as essentially an effort to evergreen aspirin. They can also keep advertising the brand name drug and hope to persuade people it is better than the generic, viz. Lipitor. (There is absolutely no reason that I can see for anyone to pay for Lipitor with very cheap generics available that are biologically equivalent. But remember, I'm not a real doctor.)

Here's some information about all this on the FDA's web site.

So, to clarify a recent flapdoodle, the FDA had given conditional approval to market Avastin for metastatic breast cancer on condition the manufacturer conduct additional trials to demonstrate that it really works. It turns out it doesn't, so approval for those specific claims has been withdrawn. However, Avastin is still licensed and approved for other indications, so doctors can still prescribe it to women with metastatic breast cancer if they want to. The question is whether insurers will pay for it. Presumably, once the appeal period is over, and if it is unsuccessful, Medicare will not.

That's why Genentech is unhappy. But it's a) still licensed and b) still under marketing exclusivity.

Then there's the whole question of so-called "supplements," which we'll get to another time. . .

They'll keep spouting this nonsense . . .

. . .until somebody stops them. The FDA has decided to withdraw approval of Avastin for metastatic breast cancer. Their reasoning, which I know is unspeakably cruel and atrocious, is that it doesn't work. Women who are given the drug for that purpose live not one day longer, and often suffer unpleasant side effects. This means that once the decision is final (Genentech can appeal) Medicare, and most likely private insurers, won't pay for it. Which is a good thing for the rest of us, because it's all of our money, and it could be going to safe and effective treatments instead. You can already guess what the Republicans are saying, those champions of fiscal responsibility, implacable foes of wasteful government spending, and defenders of freedom.

Reporting by NYT's Andrew Pollack:.

The F.D.A.’s decision also drew political criticism, with some Republicans contending that withdrawing this treatment for breast cancer was akin to rationing under the new health care law.

“It is troubling that women in Germany and France will soon have access to a life-saving drug, while women in the U.S. will not,” Representative Kay Granger, a Texas Republican, said in a separate statement.

When will the corporate media, and the people, catch on that these people don't actually believe a single word they say. They don't give a moldy fig about the federal deficit, wasteful spending, or for that matter Medicare or your health. They only care about their corporate masters. This is not a life saving drug, that's the whole point. It is, however, a money making drug for Genentech. That's the only thing that matters to Kay Granger.

First Principles

Apologies. I missed yesterday because my life was just too hectic. Right now I'm living in two different places and working (mostly) in a third, gradually disentangling myself from one home and trying to get established in another, finding my way in a new work environment and taking on new projects, and commuting more than 1 hour every day, which I have never done before and don't care to continue. Meanwhile, just getting the normal stuff done -- from auto maintenance to doctor appointments (yeah, I get doctored) to shopping -- is complicated and requires advance planning about where I am going to be and how I am going to get there. Add to that several recent Mondays in Baltimore and it's very draining.

I'm not complaining, not at all. All this is in service of an opportunity I chose to accept, and it will all get sorted out and settle down in due course. But it leads me to reflect a bit on what health really means and how it is produced. We have some conventional measures of population health which are awfully crude -- infant mortality rate, life expectancy.

We can look at age adjusted rates of specific illnesses, if they happen to be available for a given society, although these are generally very much distorted by what we call ascertainment bias. You don't have diabetes unless you've been diagnosed. So one population might have a higher rate of diabetes than another because the people are more likely to have insulin resistance and hyperglyecmia; or because they are more likely to have doctors who do tests and end up telling them that they have diabetes.

The simplest thing to do is ask people how healthy they think they are. The simple question, "Compared to other people your own age, would you say your health is excellent, very good, good, fair or poor" is actually strongly predictive of life expectancy among older people. But why do people answer as they do?

Many people do not take pills their physicians prescribe, even inexpensive ones with few or no discernible side effects, even though the doctor has told them, and they may well believe, that they're likely to live longer if they take them. Maybe it's just not worth the hassle, or they'd rather spend the $15 a month copay on something else, or life is better if you just don't worry about too much stuff.

One of the strongest determinants of population health, as conventionally measured, is social inequality. Egalitarian societies are healthier, even if the average level of wealth is lower, within a pretty wide range of total affluence. And, up to a point, richer people also say they are happier, on average -- although plenty of not so rich people also claim to be happy and lots of rich people aren't.

My affluence is slightly above average, and I don't have any diagnoses of major diseases. I have a bit of osteoarthritis as most of us do as we grow older, but it really doesn't stop me from doing anything except maybe running marathons. My life is satisfying in some respects but not others. What's missing is actually important, but it can't be fixed by doctors.

I am really unhappy, though, because of what I see happening around me. I'm in a reasonably good position to weather the storms ahead but most people are not and we may well be headed for very unpleasant times. This disturbs me greatly. So am I healthy? I could go to a psychiatrist or psychotherapist and discuss my angst. I don't think I would get a disease label but you never know. In any case, what would be the best investment in my health and that of the people around me? Should it focus on the services of physicians and the goods they purvey? If not, what should be a higher priority use? If we spend less on medicine, what should we spend more on?

Those are probably more important questions than the ones I usually discuss here.

The Truth is Out There

I've been re-reading The Bias of Science by Brian Martin, published in 1979, which figured in my master's thesis. (Which, by the way, was titled Which Way is Up? Social Welfare and the Ideology of Progress.) I find that some of Martin's monograph holds up okay, some of it not so well. But it strikes me that overall, there's been a fairly radical reversal in the zeitgeist in just 30 years.

Martin builds a political and social critique of the scientific enterprise around a dispute which is nearly forgotten: whether it was wise to operate a large fleet of supersonic transports (SSTs). Proposals for SSTs were promoted in the 1970s in the U.S., Britain, France and the Soviet Union. They were controversial mostly on environmental grounds -- opponents were worried about sonic booms (unquestionably real) and the possibility that emissions of oxides of nitrogen from jet engines in the stratosphere would deplete the earth's protective ozone shield. Martin closely analyzes two scientific papers, one supporting the danger of ozone depletion and the other minimizing it, and finds them both tendentious in various ways.

One key point of Martin's critique is that a debate framed almost entirely as environmental directed attention away from economic issues. It scarcely seemed remarkable at the time that a large public investment was needed for the SST even to be possible, and it is interesting that he doesn't even seem to notice this. It would surely be noticed today. But regardless of where the money was coming from, did it make sense to put what would in today's terms be many of billions of dollars of R&D and production costs into a means for rich people to save a couple of hours on a transatlantic flight?

As it turns out, the economic question took care of itself. In the end, only 20 Concordes were every built and they were retired in 2003 because there weren't enough rich people willing to do that after all. The U.S. program never happened, and the Soviet program was a failure that never operated commercially.

I hope to discuss Martin's work in some detail eventually, but for now I want to notice One Big Thing. Back in the ancient world of the 1970s, there was a substantial critical movement both within and outside of science that viewed the scientific enterprise as largely a creature of corporate and elite power. This was partly based from within a broad acceptance of the philosophy of science, but attentive to the selection of scientific problems, and the way in which findings were promoted, suppressed, and interpreted to serve privileged interests. It was also partly based in more radical "post modernist" critiques which contended in essence that all interpretations of reality are at least to some degree arbitrary and which even seemed to deny the existence of objective reality. Martin mostly wants to be in the first place, but he at least sets foot in the second.

Nowadays, however, there is something wrong with this picture. Nobody can claim that science, on balance, is a tool of corporate interests, when the corporate party in the United States is an implacable enemy of a large swath of scientific understanding. Corporate power never managed to recruit more than a small minority of scientists, mostly people whose careers had failed to develop within mainstream scientific institutions, to its well-funded campaigns to deny the health effects of tobacco, or lead pollution; the environmental effects of acid rain, mercury, and fine particle pollution; or more currently, anthropogenic global climate change.

To be sure, the corporate media were seduced by these campaigns for a while, and still are by global climate change denialism, but ultimately the scientific consensus won out in the earlier cases, as it surely will in the latest. We have seen that in an important applied area of science, evaluation of new drugs and medical devices, corporations have succeeded in suppressing findings unfavorable to their products and manipulating and cherry picking data that favor them. But it turns out that there was enough countervailing pressure from university and even government experts that they are finding this more and more difficult to do. (It doesn't hurt that they keep getting successfully sued either.)

It turns out that for all that it proceeds by fits and starts, goes down blind alleys and stumbles over falsities, over time science does converge on ineluctable truths. The world really is a certain way, it really does make certain kinds of sense, and if you keep hacking away at it you will find that out. It is what it is. And if that happens to be uncongenial to the Koch brothers, all of their billions cannot change it.

Unlike Glenn Beck and Sarah Palin . . .

I'm not a scholar of constitutional law. However, I can have an opinion about the practical, common sense implications of policies. The "individual mandate" to purchase health insurance has been the main focus of lawsuits by teabagging state attorneys general claiming that the Patient Protection and Affordable Care Act is unconstitutional. Now that the co-owner of a right wing consulting firm that made money in the past year by opposing the act, who also happens to be a federal judge (who would have thought that was permitted?) has ruled the individual mandate violates the constitution, there is much rejoicing to starboard. Most experts think the ruling is insupportable, and several judges have already dismissed similar lawsuits, but given the makeup of the Supreme Court, we would be very unwise to depend on what most lawyers understand to be the law.

That said, the only reason we have the individual mandate, instead of tax funded insurance, is because of the prevailing ideology. The difference is essentially semantic -- we have all sorts of federally required individual mandates. For example, I am required to pay for pieces of missiles and agribusiness profits. If I were required to mail checks to Raytheon and Dole, it might feel more offensive, but except for the price of the stamps it would pretty much amount to the same thing.

So we got the individual mandate, which requires us to mail checks to Aetna and WellPoint, because that seemed less "socialistic" than single payer national health care. The wingnuts don't like it anyway, so they're suing. But there would be absolutely no constitutional question whatsoever about raising taxes to pay for health care, which after all the federal government already does, just not universally.

The individual mandate is a much worse alternative for all of us, because a chunk of our money goes to the socially useless, parasitic insurance industry; it is much more difficult to create a properly progressive financing regime; and it is much more difficult to promote efficient and effective use of resources and stop the relentless suctioning of our national wealth into the pockets of drug companies, medical device makers, and overpaid medical specialists, among others.

I don't know about you but personally, I'm not giving up. With a Democratic House and Senate in 2013, we can fix this mess very easily by introducing a public option. Between now and November of 2012, we need to keep working to reframe the terms of this debate and purge the bullshit.

It can be done.

The slipperiness of truth

For much of the 20th Century, as scientific discovery and technological innovation were the dominant drivers of social change and major intellectual preoccupations, the generally accepted philosophy of science was positivism. I'm not going to go into any detail on that here (but you can read some of my past discussion here and in the links therein embedded). I just want to make a simple point: the central idea of the verifiability of scientific assertions runs into trouble when you get to probabilistic statements -- which, as it turns out, probably most scientific assertions happen to be.

Scientific inquiry relies heavily on statistics, notably so in epidemiological and clinical research. But think about it. When the weatherbot on your local teevee says "There is a 50% chance of rain tomorrow," how do you decide whether that assertion is true? Whether or not it rains tomorrow is no help, obviously.

Even if you follow the weather forecasts and the actual weather for a long time, you can't quite tell at what point you start to believe that the forecasters are making accurate predictions. If it rains 52% of the time they say there's a 50% chance, they haven't been exactly right but maybe that's just bad luck and it will even out the next few times.

The squishiness of probability creates a big fat opening for bias -- unconscious or deliberate -- in the presentation of clinical trial data. For the story I am about to summarize I rely heavily on Melanie Newman in the Dec. 11 BMJ, which sadly I cannot link to as it is behind the subscription wall, but here are the first few paragraphs.

The key question is a debate over the circumstances under which published research should be officially "retracted," which means in essence that the journal declares the paper no longer to exist as peer reviewed science, and it centers on a single paper published in 2001 in the Journal of the American Academy of Child and Adolescent Psychiatry, reporting a clinical trial sponsored by the company which is today Glaxo Smith-Kline of its anti-depressant paroxetine. The paper claimed the drug was effective for treating depression in adolescents.

The problem is that based on the 8 outcomes specified in advance, it was not more effective than placebo. These included 2 so-called "primary outcomes," which were the change in the average score on a questionnaire called the Hamilton Rating Scale, and the proportion of subjects who met a threshold for improvement after 8 weeks. So what did the investigators do?

They cooked up 19 new secondary outcomes, and found a positive response on four of them, one of which they then proclaimed, ex post facto, to be "primary." The manuscript was actually drafted by a company contractor, after an internal memo declared that it would be "commercially unacceptable to include a statement that efficacy had not been demonstrated."

Although all this is now publicly known, the journal refuses to retract the article because they claim it does not include any false results. Whether this assertion is itself true is essentially imponderable. Yes, all the numbers shown in the tables are accurate, and so are the p values based on the calculations that were actually done. But to say that the p values are accurate is to fundamentally misunderstand the concept of statistical significance.

It is supposed to represent the probability that an observed difference could have arisen purely by chance, without representing a real association in the total population. But that only works if I make a single comparison (assuming I don't have any information about prior probability -- which gets us to Bayes theorem, which is really where we always ought to begin anyway, instead of with p values. But I digress.) If I make 21 comparisons, as in this case, chances are I'll hit on some ostensibly "significant" p values (which is an arbitrary standard to begin with) purely by chance. The values aren't really significant after all.

So the numbers in the paper may be true in some sense; but the conclusions are false. Their meaning has been fundamentally misrepresented. I don't know if that means the paper should be retracted, however -- if we start going down that road we're going to have a massive bonfire.

Mission Accepted

You may have seen a link to this posting by M.S. on The Economist blog, which has drawn some blogospheric attention. Only 6% of scientists identify themselves as Republicans, compared to 55% who identify as Democrats. M.S. wonders why:

I can think of three testable hypotheses they might look into. The first is that scientists are hostile towards Republicans, which scares young Republicans away from careers in science. The second is that Republicans are hostile towards science, and don't want to go into careers in science. The third is that young people who go into the sciences tend to end up becoming Democrats, due to factors inherent in the practice of science or to peer-group identification with other scientists. In the absence of data, I leave it to you to decide which you find most plausible. But by all means, social scientists should look into this.

Hey, I'm a social scientist! But I don't have to look into it, I already know the answer, and it's None of the Above.

Scientists study reality, carefully applying rigorous methods of data collection and rules of inference. They think from evidence to conclusions. I don't need to tell you that reality has a well-known liberal bias. That's why conservatives don't go near it. They reason from a priori principles to decide that reality must be whatever they need it to be in order to believe what they already believe, which isn't actually true. So they can't be scientists.

Reap This Righteous Rant

Michael Millenson, on the Health Affairs blog, opens a can of whoop ass on the medical industry for apathy about patient safety. Since the much ballyhooed Institute of Medicine Study To Err is Human, issued in 1999, we have made essentially no progress on reducing the estimated million preventable patient injuries, and close to 100,000 deaths, in hospitals every year. (People don't even seem to think about outpatient iatrogenic injuries and deaths. I'll get to that in due course.)

Millenson's basic point is, we know how to enormously improve safety and reduce errors that harm patients, but people just don't bother to do it. Hospitals eschew opportunities to join programs to enhance safety, because their administrators think they're already just so fabulous, or they are worried that by trying to do better it will look like they are admitting they have a problem, or . ..

They actually make money by harming patients. That's right: when people suffer avoidable complications, such as catheter associated infections, the hospital gets paid more to take care of them. Of course if the patient dies they might earn less due to the shortened stay, but that's usually a risk worth taking. Millenson doesn't mention that Medicare is trying to change reimbursement policy to eliminate this perverse incentive in certain readily definable and obvious cases, but in general, it's still true. (It was true in my own case, BTW, when surgeons erroneously removed my ascending colon and then fed me while my bowels were still paralyzed, and oh yeah I got nosocomial C. difficile. Then they sent me a bill for $25,000. I told them to fold it until it had as many corners as humanly achievable entonces metelo donde el sol no brilla. But they tried. But I digress.)

The way to fix this, of course, is the way civilized countries fix it: put hospitals on a global budget to take care of the population of their catchment area. Everybody gets a salary, and nobody makes a profit, but people can get bonuses for doing good stuff. That way, the incentives are to deliver care as efficiently and effectively as possible. And oh yeah, they have to meet the standards of the single payer, whether they like it or not.

But no, that would be socialism. So don't even think about it. Just shut up and die.

Anecdotal evidence

I can't answer Daniel's question about what percentage of medical spending in the U.S. is for stuff that we just shouldn't do in the first place, but this story in Health Affairs illustrates the problem. A 90 year old man with dementia, heart disease, and diabetes, goes through hospitalization, surgery, multiple tests that cause serious complications, in and out of a rehabilitation facility, all of it costing more than $200,000, and none of it doing him a damn bit of good. He dies six weeks later.

There isn't any corruption, and not even any significant misaligned financial incentives behind this debacle. It's largely a function of our medical culture -- shared by physicians and the public, in this case as represented by the patient's daughter -- which just assumes that doing more is better and leaving well enough alone is irresponsible. And oh yeah, that we must never just accept death.

Listen up buster. Death is unconquerable, at least as of 2010. So is getting older. Get used to it.

Cheap, completely understood, and it works

That would be aspirin. I wrote about it a long time ago, the message being that drug companies invested a lot of money in (as it turns out bogus) research and marketing in order "evergreen" aspirin. Since the patent on aspirin was gone before I was born, it sells for bupkis and anybody can make it. Ergo, Pfizer and Merck couldn't make any money off of it. Hence we got the debacle with the Cox 2 inhibitors, which were supposed to do all the good of aspiring with less risk of gastrointestinal side effects.

Sadly, no, as it turns out, because aspirin reduces the risk of heart disease and ischemic strokes, whereas the Cox 2 inhibitors increase it. I'd rather have an upset, or even bleeding stomach (generally reversible if you just stop taking the aspirin) than drop dead. And I have always felt that the side effects were overblown as a result of the drug companies hyping them in order to justify their much more expensive products. I'm not a real doctor, so don't rely on that judgment -- and for sure, not everybody can take aspirin. But at low doses, it's unlikely to cause problems.

There's no money to be made from aspirin, so it's hard to fund studies. As you may have heard, these docs in the land of the brolly and bowler hat did a secondary analysis of data from trials originally intended to determine the cardiac benefits of aspirin. Turns out it is also fairly effective at preventing many cancers. Not dramatically -- about a 20% reduction in risk of death from cancer over 20 years, and only if you keep at it for all that time. 75 mg a day will do it, more is not better!

Yes, there can be side effects but it's one more thumb on the scale in favor of more people considering this. (As always, ask your doctor, and I don't mean Dr. Ruth.) By the way, although salicylic acid is famous for being found in willow bark, it and similar compounds are found in many vegetables, which may help account for the overall goodness you get from eating lots of them. Just a speculation on my part, but it looks good.

The real lesson here is that aspirin was a miracle drug 100 years ago, but we haven't studied it nearly enough because there was no money to be made from it. If the drug companies had invested in understanding more about aspirin, instead of trying desperately to find something patentable, we would have gotten this news a long time ago. But of course they never will, because the Free Market™ doesn't allocate sufficient resources to basic research that can benefit humanity. Only government can do that, because knowledge is a public good.

It's Ecomomics 101 time again . . .

From the NY Times, a disgusting story about a cardiologist who was implanting stents, by the hundreds and thousands, in people for whom they were not indicated. As you may recall, these devices don't actually reduce your risk of heart attack or death. At best, they relieve the chest pains which can be a symptom of cardiovascular disease. In our last episode, we learned that many patients who receive them have the impression that they do in fact reduce the risk of heart attacks and extend lives. Did they just misunderstand their doctors?

Or did their doctors lie to them? From the Times article:

Edward Chaid, 68, a semiretired general contractor from Timonium, Md., is among those who have sued. Five years ago, Mr. Chaid decided to get his first physical examination in decades. Just to be safe, his doctor sent him for a cardiac stress test at MidAtlantic, which revealed a small “squiggle” of concern, Mr. Chaid said. He was sent to Dr. Midei to get his arteries X-rayed, and he emerged from the procedure with two stents.

“Dr. Midei said: ‘You sure are lucky. You had 90 percent blockage.’ And the nurse said, ‘Oh yeah, you were blocked in your widow-maker.’ And I said: ‘Thank God. I guess I’m really lucky you got it when you did,’ ” Mr. Chaid said in an interview.

Actually Mr. Chaid didn't even have a severe blockage, but even if he had, if he didn't have chest pain, there would be no reason to implant the stent.

I'll leave it to interested persons to read the Times article for all the gory details of this story, which also involve Abbot Labs and the hospital as unindicted co-conspirators. But for our purposes the point of this story is that once again, it proves that neoliberal economics is completely disconnected from reality.

Libertarians and their allies in the Theology Economics departments of our major universities envision buying and selling transactions as necessarily benefiting both parties. The problem of externalities, which we have often discussed, does not enter into this. We're talking about the internalities, as it were. According to standard economic theory with which college freshmen are indoctrinated, the money gained in the transaction must be worth more to the seller than the goods and services rendered; and they must in turn be worth more to the buyer than the money. Otherwise the transaction would not take place. So everybody wins. Not only that, but consumers are sovereign: they create the demand which calls for the productive potential of the economy. If people didn't want stents, not so many of them would be made, and not so many hospitals and cardiologists would share the $10,000 a pop they get for implanting them.

The problem, obviously, is that you and I don't have the slightest idea whether we would benefit by more than $10,000 from a stent. Let's even leave aside the issue of third-party payment. If somebody told me I needed it to save my life, I'd come up with the ten grand somehow on my own, if I possibly could. How was I supposed to know the guy was a greedy psychopath who was lying to me so he could pocket the fee?

This is obviously an extreme case. The medical industry could not function at all if physicians didn't have a code and a culture of ethics that we know we can rely on. We have to trust our doctors and most of the time, they are basically trustworthy. Still, if there is money to be made, they are likely to be swayed unconsciously in the direction of doing more. And the culture of their specialty will, again without conscious bias or awareness of pecuniary motives, tend to lean toward valuing what they do highly. No surprise, if you are diagnosed with prostate cancer, surgeons will think you need surgery, radiologists will think you need radiation, and oncologists will think you need chemotherapy; but maybe what you really need is nothing.

This is why it is ridiculous for conservatives to try to scare us with the specter of government bureaucrats coming between us and our doctors. We and our doctors need the best possible information about what treatments are indicated and cost effective under what circumstances, and they need some guidelines to keep everybody at least in the ballpark of doing the right thing. Without that, we don't just waste money, we get physically assaulted and maybe seriously harmed, if we happen to stumble on an amoral greedhead. Free Markets™ and liberty have nothing to do with it.

A doctor of the wrong philosophy

Benjamin R. Barber, Walt Whitman Professor Emeritus at Rutgers, writes in the November 29 Nation (subscription only) on "America's Knowledge Deficit." He hits the spot with me on his main point, that an "epistemological deficit . . . is putting Democracy at risk." He writes that

[F]ar too many Americans, including not just many of the new Tea Party politicians but established leaders like former president George W. Bush, honestly think the difference between, say, evolution and creationism is merely a matter of opinion: you think man is descended from apes; I think he is a creature made by God. Tolerance, to Bush, means we respect both views and acknowledge their common creditability, because, after all, we both feel deeply about the matter -- which means, in turn,we teach both views in our schools.

Well yes, except that man [sic] is not descended from apes. Prof. Barber needs to brush up on his evolutionary biology. Humans and apes have a common ancestor, which was not quite ape and not quite human. It is most accurate, probably, to say that we are apes. But this is a common misconception, which I will forgive.

However, Barber goes more seriously wrong:

There are, of course, many issues that cannot be judged by empirical evidence or objective truth. The existence of God is one of them. These are normative rather than empirical claims. . . . When as an evolutionist I claim man is descended from apes . . .I am claiming something that can be corroborated or falsified by reference to fossil records, genetic affinities, geology and other kinds of empirical data and testable hypotheses. When I claim God created man and then woman from the rib of man, there is no way to confirm or falsify this claim, no "evidence" that can counter what is subjective belief.

Err, no. The claim that God made "woman from the rib of man" is as false, and as falsifiable, as the claim that "man" is descended from apes. Religious beliefs about the nature of reality and the history of the world are completely falsifiable, and almost always false, because they derive from faulty epistemology. Barber has adopted the unfortunate attitude of many people who want to adopt the stance of reason but don't want to offend religious people by pointing out that there beliefs are, quite obviously, false. For some reason we just can't say that, so we need to put them in a separate category where "truth" means something different than it does in, well, reality.

This is just silly. God did not make a woman from the rib of a man, there wasn't any Noah's ark, and Jesus was not born of a virgin and did not walk around accosting people after he was dead. These assertions are objectively false and can be disproved by resort to our senses and reason, just like every other objectively false assertion. And believing in falsehood is bad for you.

Site news: I have indeed established a new blog, called Windham County. There isn't much there yet, but I'll be posting material there that doesn't really belong here, to keep Stayin' Alive clean and on topic, at least somewhat. Let me know if people want to exchange links. (The Dharma Bums get a freebie.)

Stuff

This is more of a personal note than I usually write here, but I want people to know what's going on with me. As I have at least hinted, I'm in the process of gradually moving out of my home of more than 20 years, taking stuff one pickup truckload at a time to my country place in Connecticut. As soon as I can sell the property in Boston, I'll get a pied a terre of some kind near my new workplace in Providence. It's obviously done with mixed feelings. My underlying reluctance is making it go more slowly than it needs to.

But there's also something healthy about it. I'm finding out what I have -- a lot of old junk and paper that has existed in my space for years or decades for no particular reason, it turns out. I'm throwing away more than I expected, although it's often a close call. On the other hand, it's just as often the case that I have no idea why I kept something in the first place. For some reason, I had several newspapers and magazines from what, as far as I can tell, were unremarkable days in 1999. A lot will be recycled but a lot will also go to the landfill. At least it's mostly non-toxic, except maybe for all the toner cartridges from an old photo printer that doesn't work any more. (And how the hell do you ethically dispose of electronic equipment, anyway?)

But I'm also discovering things I'd forgotten about, that are worth keeping, and that also remind me of past thoughts, plans, ideas -- some of which, who knows, might be reborn one day. I'm keeping some material that's just autobiographical evidence -- reminders of past events, people I knew, observations of the day.

Anyway, I'll end up not only traveling through life a little bit lighter, at least until the accumulation returns to its present level; and also a little more in touch with myself, a little bit better organized, and if I don't lose momentum, a lot tidier. Still, it's kind of sad.

It's Economics 101! (The Continuing Series)

Government regulation stifles economic growth and innovation. Lift the dead weight of government from the backs of our entrepreneurial class and we'll all be more prosperous and free. And oh yeah -- I'm actually Brad Pitt.

Commissioner Margaret Hamburg reviews the history of the FDA in the new NEJM, which, quaking before the mighty power of Stayin' Alive, makes her essay available to you, the undoctorated. As Hamburg tells us, before the FDA came along, heroin was marketed as a remedy for coughs and asthma. It does actually work, unlike most of the crap that was sold as medicine in those days.

At first though, the FDA couldn't require proof of safety before medications were marketed. In 1937, a company sold sulfanilamide (an antibiotic) in a solution of diethylene glycol, otherwise known as antifreeze, which as you probably know is not good for you. In fact it killed more than 100 people. So Congress passed the Food, Drug and Cosmetic Act to require prior evidence of safety. The FDCA, by the way, spared the United States from the Thalidomide disaster which resulted in thousands of babies born with severe birth defects in Europe.

It wasn't until 1962, however, that the FDA could require good evidence of effectiveness before approving drugs and approving marketing claims. One third of drugs then in common use ended up being withdrawn from the market because they just didn't work.

It was regulation that spurred the immense explosion of pharmaceutical innovation since that time. Only when they were required to develop good scientific evidence of safety and effectiveness did drug companies actually start spending the money to get it -- big investments that have had big payoffs for human health.

We still have a long way to go -- publication bias, me too drugs, and aggressive marketing of drugs that are no better or even worse than their cheaper competitors still plague us. We need better, stronger regulation. But it's the regulation we do have that has spurred scientific knowledge, technological development, and the wealth generated by the pharmaceutical industry. Without it, we'd still be swallowing snake oil.

BTW, the specific flaw in the totally bogus theory of the Free Market™ in this case is the requirement of perfect information. Consumers don't have information about whether drugs are safe and effective unless the government requires it. That's why we need government intervention in the market to give us drugs that help, rather than hurt us. There's no other way.

Minority Report

I've just gotten done participating in a proposal review process. I'm not allowed to say anything specific about it, and I know that specificity is the essence of good story telling, so this will just have to be a badly told tale. Still.

I really didn't like the proposal, but everybody else did. The basic reason was that I couldn't see any good reason to do undertake the experiments the investigators proposed, whereas the other reviewers do the same sort of thing themselves so naturally they weren't very open to the idea that it's all basically pointless.

To get slightly more specific, this has to do with the existence of some new high tech toys that allow people to make observations that sound like they ought to be really cool and might even be like really wild cool stuff that you read about in science fiction -- to be even more specific, reading people's minds.

That's about as specific as I can get but here's the bottom line. We know that stimuli get registered in the brain, and that the brain creates experience, such as specifically pain. So if people are in pain certain parts of the brain are more active, and if they are in less pain those places are less active. On the other hand we don't know what pieces of that, if any, have to do with the conscious experience of pain, because most of what goes on in our brains does not impinge on our consciousness. And just looking at the pictures will never, ever tell us. And for that matter, even if it could, what would it mean other than, these are the part of the brain that are active when we are in pain, and these are the parts that are associated with our conscious experience of pain. If I do something that results in people reporting less pain, I would expect the images of their brains to be like the images of brains of people who report less pain. So what?

Apparently so something, even though they couldn't really explain it to me. So this will probably get funded. Oh well.

Good science isn't about fancy toys and stuff that only a few people know about. It starts with asking the right questions. And that's not just a matter for scientists -- it ought to be a right of the people.