The health marketplace has a life of its own, mostly separated from science and evidence. Generally the marketplace gets a hold of an idea and runs with it, before the science is carefully worked out. Since most new ideas in science turn out to be wrong, that means most products will eventually be found to be worthless.

One such idea is that “brain training” can improve overall cognitive function – so of course now there is an industry of products which claim to train your brain. Lumosity (just to pick a random example served up by Google) claims on their website:

Brain Train
SCIENTIFICALLY DESIGNED

* Improve memory and attention
* Shown to improve cognitive function
* Neuroscience based brain training
* Train your brain today

I always enjoy the phrase “scientifically designed” or “scientifically formulated” – they are wonderful marketing phrases that invoke “science” without making any specific claims.

The notion of improving brain function by practicing certain tasks or playing cognitively demanding games is an attractive one. I certainly would like this to be true: get smarter while playing video games – I’ll buy that for a dollar.

It also may or may not be plausible, depending upon how you look at it. What is uncontroversial is that the brain learns, and practice does improve function – no question. But, the evidence also suggests that genetics is a dominant determining factor of overall cognitive function – we all eventually seek our maximum potential. (This does not apply to knowledge or skills, but raw brain power in specific areas.)

Prior studies, both observational and experimental, have shown a correlation with playing certain kinds of games and cognitive ability. For example, one study showed that playing Half Life (a first-person shooter featuring physicist Dr. Gordon Freeman) significantly improved surgical skill performing virtual reality endoscopy.

Another study showed improvement in “executive control functions, such as task switching, working memory, visual short-term memory, and reasoning,” from strategy video game playing. And yet another study showed improvements in visual processing from playing action video games.

But questions remain. For example, how transferable are the skills learned from video games? Do subjects improve only in their ability to play the specific video game and closely related tasks, or does brain function improve in more abstract ways not directly tied to the video game?

Also, how much game playing is necessary? Does benefit come only from playing hours a week, and over months and years, or can more modest “training” be beneficial? And further, is self-selection bias primarily responsible for some of the positive results? In other words, are people who are already superior at certain tasks playing video games because they are good at them and therefore enjoy them more?

With this in mind, Adrian Owen et al. set out to conduct a large study of specific brain training products (not video games optimized for fun) on four standard measures of cognitive function: grammatical reasoning, verbal short-term memory, spatial working memory, and paired associates learning. They randomized 4,678 subjects to three arms – one group was trained on programs designed to enhance reasoning, planning, and problem solving. The second group was trained on memory, attention, visuospatial processing, and mathematical calculations. The third group, the control, was given five obscure knowledge questions and asked to use the internet to find the answers.

Each group was tested at baseline and after six weeks, regardless of how many training sessions they completed, but on average the first “treatment” group completed 28.39 training sessions, compared with 23.86 in experimental group 2 and 18.66 in the control group. At the end of the study there were no statistically significant differences among the three groups – all improved slightly in all four measures.

The mild improvement is almost certainly due to the training effect – this is seen generally in studies of cognitive function or studies that use performance on a task as an outcome – subjects get better just from experience. That is why control groups are always needed.

The study showed that the subjects improved in the tasks on which they were training, but that these improvements did not generalize or translate to the benchmarks of cognitive function. This is a fairly solid study with a clearly negative outcome.

Conclusion

This one study, of course, is not definitive. It is possible that more training is needed before significant benefits are seen. Perhaps video games are more effective because they are more engaging and players will spend more time playing.What this study shows, however, is that products sold as brain training games had no documented benefits after six weeks of use.

Putting this study into the context of the overall research, it does make us more cautious about concluding that there are general cognitive benefits to brain training games or entertainment video games. Benefits are likely to be closely related to the specific tasks involved in training, and not transfer to unrelated tasks.

But there is already enough published evidence showing visual tracking, multitasking, and executive function benefits from action and strategic video games respectively that this study will not be the final word. When there is conflicting research, more study is needed.

This study is most applicable to brain training products, and shows that the marketing claims for these products are not justified. There is very unlikely to be any benefit, or any specific advantage, to “scientifically designed” brain training applications. For now, you are better off just playing a video game.

Long live Gordon Freeman.

In his new book Breakthrough! How the 10 Greatest Discoveries in Medicine Saved Millions and Changed Our View of the World Jon Queijo describes what he believes are the 10 greatest discoveries. 9 of them are uncontroversial discoveries that have been on other top-10 lists, but his 10th choice is one that no other list of top discoveries has ever included. He realizes that, and even admits in his introduction that a former editor of The New England Journal of Medicine refused to review his book because there is no such thing as alternative medicine, only treatments that work and treatments that don’t. But he “respectfully disagrees.”

Hippocrates’ discovery that disease had natural causes, sanitation, germ theory, anesthesia, X-rays, vaccines, antibiotics, genetics, and treatments for mental disorders are all worthy candidates for the list. But Queijo ludicrously lists the “rediscovery of alternative medicine” as the tenth “great discovery.” He presents no evidence (because there is no evidence) that alternative medicine has “saved millions” or that it has saved anyone. He doesn’t realize that alternative medicine represents a betrayal of exactly the kind of rigorous scientific thinking and testing that led to all the other discoveries. His list of ten breakthroughs is actually a list of 9 breakthroughs and one breakdown.

He tells compelling human-interest stories about the discoveries. The complexities, the mis-steps, the near-misses, and the ups and downs make fascinating reading. He describes farmer Benjamin Jesty leading his wife and children on a two mile trek through the fields in 1774 to steal cowpox pus from a neighbor’s cow and inoculate his family with a sewing needle to protect them (successfully!) from smallpox. He describes the many chance events that had to conspire for Fleming to see the effects of mold on his culture plate and the long, tortuous course between his observation and the therapeutic use of penicillin. He tells how the pea-gardening monk Gregor Mendel’s discovery of genetic principles went unrecognized until decades later after 3 other researchers had unknowingly replicated some of his experiments.

He offers fascinating tidbits of historical information. Anti-vaccine activists are nothing new: he tells how they sabotaged the use of an early typhoid vaccine in the Boer War by such tactics as dumping vaccine shipments overboard from ships. As a result, the British Army suffered more than 58,000 cases of typhoid and 9000 deaths.

He recounts Roentgen’s early comments about his discovery of x-rays:

I still believed I was the victim of deception.

I have discovered something interesting, but I do not know whether or not my observations are correct.

Before he announced his discovery, he studied the characteristics of the rays, investigating whether they could penetrate various materials or be deflected by a prism or a magnetic field. One can only wish that today’s students of “energy medicine” would employ his cautious, self-questioning, and scientifically rigorous approach!

My favorite was a delightful anecdote about Thomas Edison: in the early days after the discovery of x-rays, Edison received two requests in the mail, one from an apparent voyeur asking him to fit a set of opera glasses with x-rays and the other asking him to

Please send me one pound of X-rays and bill as soon as possible.

There are hints of trouble before we get to the chapter on alternative medicine. Queijo claims that one of Hippocrates’ accomplishments was to believe that respect for a higher power was a necessary precondition for good health. What does that even mean? Why would it be important? He offers no evidence that such respect has ever saved lives or had any positive effect on medical practice.

In the chapter on genetics, he starts by describing the ancient superstition that “maternal impressions” could affect the development of the fetus: for instance, after watching a fire, a woman delivered a baby with a flame-shaped birthmark. He demolishes that possibility with a reasoned discussion of genetic principles and DNA. But then he inexplicably cites a modern study by Ian Stevenson, who holds a number of strange beliefs, is convinced he has solid evidence proving reincarnation, and could be classified as a maverick if you wanted to be polite. Stevenson collected a number of case reports and opined that

In rare instances maternal impressions may indeed affect gestating babies and cause birth defects.

Queijo agrees with him, saying

In the brave new world of genes, nucleotides, and SNP’s it’s easy to dismiss such mysteries as playing no role in the inheritance of physical traits — no more than, say, DNA was thought to have for 75 years after its discovery.

He’s wrong: Stevenson did not find any “mysteries” but merely the kind of coincidences that will be inevitably found if you look hard enough for them.

In the chapter on alternative medicine, Queijo loses it entirely. He seems to think that modern medicine has become so fixated on diseases and technology that alternative medicine had to rediscover that diseases occur in people. He criticizes the reductionism of the scientific approach, but offers no evidence that a non-reductionist approach has ever resulted in discoveries or provided better patient outcomes. He sees the struggles between scientific medicine and alternative medicine as politically motivated turf wars rather than as efforts to establish the truth. He claims that by 1998, Americans were seeking alternative care practitioners more often than their own primary care physicians. If this is true, offering that statement without qualification would be misleading to say the least. Anyway, popularity is no guide as to what treatments work.

He accepts homeopathy uncritically and even suggests that it is now supported by science. He likes the idea of homeopathy because it “shares some underlying values seen in ancient traditional medicines” such as vitalistic energy concepts, detailed interviews to inquire into every detail of the patient’s life, stressing the healer-patient relationship, and deriving many of its remedies from natural products.

He says,

Alternative medicine offered something Western medicine had too often abandoned: the view that every patient was an individual, that natural treatments were sometimes better than dramatic surgery and dangerous drugs; and that the essence of medicine begins with a caring relationship between healer and patient.

This is a straw man argument that badly mischaracterizes mainstream medicine, and it fails to show that alternative medicine has any advantage over scientific medicine practiced with judgment and empathy. If every patient is an individual and the whole person should be treated, why do chiropractors fixate on adjusting spines and acupuncturists fixate on improving the flow of qi through meridians?

He even goes as far as to accuse the stethoscope of being a nefarious device that distances practitioners from patients! He calls its invention “a dark omen for the terrible turn Western medicine was about to take.” Now, really!

Much of this book is an eloquent paean to the value of science. Unfortunately, it abandons science in its discussion of alternative medicine. It deteriorates into apologetics for belief-based medicine based on misunderstandings and opinions rather than on any evidence. Alternative medicine represents a breakdown of the process that led to the real breakthroughs.

If you read this book, I recommend skipping chapter 10.

Editor’s Note: Having pivoted immediately (and dizzyingly) from attending NECSS and participating with John Snyder, Kimball Atwood, and Steve Novella in a panel on the infiltration of quackery into academia to heading down to Washington, DC for the AACR meeting, I’ve neglected my SBM duties a bit this week. After a packed day of talks at the AACR meeting followed by spending an evening with a friend whom I haven’t seen for a long time (complete with a trip to The Brickskeller), there’s–gasp!–no new material today. Because for some reason a decision was apparently made to cut our panel very short in order to get the conference back on schedule, we were unable to answer anywhere near as many questions from the audience as we had originally hoped, I was thinking of doing a post trying to answer a couple of the questions asked by audience members who came up to me after the panel terminated prematurely, because one of them was a particularly dicey situation. Maybe later this week. In the meantime, here’s something that I wrote about a year ago, which I tweaked a bit. It’s a very serious topic, but I think it appropriate because it discusses exactly what science-based medicine tries to prevent using evidence and what “alternative medicine” claims it can prevent based on no evidence.

I’ve written before about the Daniel Hauser case, a 13 year old boy who last year refused chemotherapy for his Hodgkin’s lymphoma, necessitating the involvement of the legal system. Cases like that of Daniel Hauser reprsent supreme “teachable” moments that–fortunately–don’t come along that often. The antivaccine movement, for instance, will be with us always (or at least, I fear, as long as I still walk this earth and beyond), but cases like that of Daniel Hauser tend to pop up only once every couple of years or even less. As tragic as they are, they always bring up so many issues that I have a hard time leaving them alone.

This time around, I wanted to touch on an issue that has come up frequently in the discussions of this case, and that’s the issue of chemotherapy. Specifically, it’s the issue of how horrible chemotherapy can be. Again, make no mistake about it, chemotherapy can be rough. Very rough. But what is often forgotten is that it can also be life-saving, particularly in the case of hematologic malignancies, where it is the primary therapy. What is also often forgotten or intentionally ignored by promoters of unscientific medicine is that doctors don’t use chemotherapy because they have some perverted love of “torturing” patients, because they’re in the pockets of big pharma and looking for cash, or because they are too lazy to find another way. They do it because, at least right now, it’s the best therapy science-based medicine has to offer, and in the case of Hodgkin’s lymphoma, for example, it’s life-saving. You can be sure that if a less harsh way were found to achieve the same results, physicians would jump all over it. Indeed, a major focuse of oncology research these days is to find less brutal regimens and improve the quality of life of cancer patients while still giving them the best shot at survival.

Yes, chemotherapy can make you feel nauseated and make you throw up. It can make your hair fall out. It can temporarily depress the immune system. It can cause bleeding complications, such as GI bleeding. It can cause kidney damage. It can cause heart damage. It can cause lung damage. It can cause nerve damage. It can make you lose weight. It can even result in your death from complications. In short, it is not something to be used lightly. Unfortunately, the disease it’s meant to fight is a formidable foe indeed. It is your own cells, and all too often the difference between the toxicity of chemotherapy against the cancer and against normal cells is not that large.

But what does cancer do? How do cancer patients die? They suffer and die in protean ways. Cancer can do everything chemotherapy can do (with the exception of hair loss) and more. I’ve seen more patients than I care to know suffer and die from cancer. I’ve seen family members suffer and die from cancer, most recently my mother-in-law last year.

One of the most frequent claims of cancer patients who opt for quackery instead of chemotherapy and effective science-based therapies is that they want to remain healthy. Some, as Abraham Cherrix did, state that, even if they end up dying, they want to “die healthy.” It’s a dangerous delusion. There is nothing “healthy” about dying from cancer. Dying from cancer is anything but “healthy.” But it is perfectly natural, as natural (or even more so) than the herbal concoctions that so many alt-med believers put their faith into. But what does dying from untreated cancer mean? What happens? What does it involve?

Dying from untreated cancer can mean unrelenting pain that leaves you the choice of being drugged up with narcotics or being in agony.

Dying from untreated cancer can mean unrelenting vomiting from a bowel obstruction. It can mean having a nasogastric tube to drain your digestive juices and prevent you from throwing up. Alternatively, it can mean having to have a tube sticking out of your stomach to drain its fluids.

Dying from untreated cancer can mean bleeding because you don’t have enough platelets to clot. The bleeding can come in many forms. It can be bleeding into the brain, in essence a hemorrhagic stroke. It can mean bleeding from the rectum or vomiting blood incessantly. And, because so many transfusions are all too often necessary, immune reactions can chew up new platelets as fast as they’re infused. Yes, paradoxically, even when a cancer patient’s immune system is suppressed in late stage cancer, frequently it does work against the one thing you don’t want it to: Transfusions of blood products.

Dying from untreated cancer can mean horrific cachexia. Think Nazi concentration camp survivor. think starving Africans. Think famine. Think having cheeks so sunken that your face looks like the skull underlying it.

Dying from untreated cancer can mean your lungs progressively filling with fluid from tumor infiltration. Think choking on your own secretions. Think a progressive shortness of breath. Think an unrelenting feeling of suffocation but with no possibility of relief ever.

Dying from cancer can mean having your belly fill with ascites fluid due to a liver chock full of tumor.

Dying from cancer can mean a progressive decline in mental function due to brain metastases.

Dying from cancer can mean so many other horrific things happening to you that they are way to numerous to include a comprehensive list in a blog post, even a post by a blogger as regularly logorrheic as I am.

Modern medicine can alleviate many of the symptoms people with terminal cancer suffer, but all too often it can’t reverse the disease process. However, the relief of these symptoms requires that the patient actually accept treatment. Hospice can minimize such symptoms, often for significant periods of time. However, even with the very best hospice care, there is nothing “healthy” or pleasant about dying from cancer. It means a loss of control. It can mean being too weak to get up by yourself, to feed yourself, to go to the bathroom yourself, to bathe yourself, or do do much other than lie in your bed and wait for the end. Without such treatment, a patient who chooses quackery over effective curative or palliative therapy dooms himself to a painful and unpleasant death. He in effect dooms himself to the sorts of ends untreated cancer patients suffered hundreds of years ago, before there was effective therapy. It doesn’t have to be this way, but the seductive promise of a cure without pain, without hair falling out, without nausea lures cancer patients to havens of quackery in Tijuana or to flee from authorities trying to see that a child obtains potentially life-saving treatment, all because of a magnified fear of chemotherapy, all because of the propaganda that paints chemotherapy as “poison,” radiation as “burning,” and surgery as “slashing.”

Here’s the dirty little secret behind “alternative cancer cure” (ACC) promises. They are seductive because it is true that cancer patients who stop their chemotherapy will feel better than they did when undergoing chemotherapy. Of course they do, at least for a while! Often what happens, as in Daniel Hauser’s case, is that the tumor shrinks, and, once the chemotherapy course is done, the patient does feel better because the tumor is no longer causing B symptoms or compressing lungs and making him short of breath, and other symptoms are also relieved. It is also true that more chemotherapy will make the patient feel lousy again for a time. Unfortunately, in the case of Hodgkin’s lymphoma, the additional chemotherapy is necessary to maximize the chance of cure. Hodgkin’s disease frequently relapses without the additional courses of chemotherapy. Science and clinical trials have told us that. Daniel Hauser is living proof, an anecdote that is consistent with what science tells us.

In other words, the promise of ACCs is a lie. They promise that cancer patients will always feel the way they do after the first course of chemotherapy is over and they have recovered or the way they feel before the tumor has grown beyond what can be cured. They are either deluded or lying. That’s because cancer doesn’t give up. It’s like the Terminator. It can’t be bargained with. It can’t be reasoned with. It doesn’t feel pity, or remorse, or fear. And, if it is not treated, it absolutely will not stop, ever, until the patient is dead. And it rarely will be a pretty end. There’s a case to be made that it isn’t worth they symptoms to undergo chemotherapy when it has a very small chance of success. Such a judgment is up to the patient, based on his or her values and an accurate knowledge of the risks and benefits, which we as science-based physicians must provide them. However, all too often, by foregoing effective palliation, patients who choose ACCs condemn themselves to an end far more brutal than is necessary even if their cancer is terminal when diagnosed, and patients whose cancer is not terminal when diagnosed give up their one best shot at life.

There is no question that the incidence and prevalence of autism are on the rise. Starting in the early 1990s and continuing to today, there has been a steady rise in the number of children diagnosed with autism. Prior to 1990 the estimates of autism prevalence were about 3 per 10,000. The most recent estimates from the CDC and elsewhere now have the number at about 100 per 10,000, or 1%.

The burning question is – why are the rates increasing steadily? There are those, particularly in the anti-vaccine community, who conclude that the increase in prevalence is a real biological effect – an epidemic – and is evidence for an environmental cause (which they believe is vaccines, even though the scientific evidence does not support this position). However, the evidence strongly suggests that the rising prevalence of autism is largely an artifact of broadening the diagnosis and increased surveillance.

It should be noted that the data cannot rule out a small true increase in autism prevalence. Some hypothesize that increasing maternal and paternal age are contributing to the incidence of autism, but I will leave that question for another post.

A new study now adds significant support to the surveillance hypothesis – Ka?Yuet Liu, Marissa King, and Peter S. Bearman from Columbia University, publishing in the American Journal of Sociology, report that the risk of being diagnosed with an autism spectrum disorder (ASD) correlates with social proximity to another family with a child with an ASD diagnosis. For those interested in this topic, the full paper is worth a read. While it gets technical at times, the authors do an excellent job of reviewing this topic in detail.

To summarize their key points – they begin by reviewing the history of the autism diagnosis. They point out that historically, in the 1950s and 60s, the diagnosis of autism was stigmatized by psychogenic theories of causation (the infamous “refrigerator mothers”). But then:

With hindsight, we can recognize that autism was increasingly destigmatized through the mobilization efforts of Bernard Rimland and the National Society for Autistic Children (NSAC), whose work refuted psychogenic theories of autism and set the stage for the research program that would identify autism as a neurological disorder (Dolnick 1998).

Therefore, prior to the 1970s parents actually mobilized their resources to avoid an autism diagnosis, and instead to seek a diagnosis of mental retardation (MR). This was not only to avoid stigma – the diagnosis of MR was attached to more public resources, while autism was left out in the cold. Then, this situation began to flip. Increasingly after 1990 ASD lost its stigma and became increasingly attached to access to public resources. Parents then began marshaling their resources to obtain an ASD diagnosis, rather than an MR diagnosis.

Liu et al discuss that this interpretation of the history of ASD makes a number of predictions, and they sought to test those predictions. They are not the first to do so, and others have demonstrated (which they review) that as ASD diagnoses increased there was diagnostic substitution – other related diagnoses, such as MR, decreased. Autism prevalence has increased uniformly in all age groups. If an environmental cause was at work, younger age groups should have disproportionately increased. When the same diagnostic criteria are applied autism incidence is largely stable over time. Increasing caseloads of ASD correlate with times when the diagnostic criteria are expanded.

The study authors now go further – looking at the pattern of ASD diagnoses sociologically. They hypothesized that if the increasing rate of ASD is due to sociological, rather than biological, factors then proximity should play a role. That is exactly what they found – a child who lives 250 meters from another child who has been diagnosed with autism is 42% more likely to be diagnosed, and if they live between 250 and 500 meters of another child, they have a 22% increased chance of being diagnosed. Basically, being close to a family with an ASD child provides access to information that allows other parents to more efficiently mobilize their resources to seek an ASD diagnosis.

This matters because obtaining an ASD diagnosis is not always easy or automatic. Many ASD children, on first presentation to a pediatrician, are not diagnosed. Some doctors are more likely to make the diagnosis than others. And school systems may delay diagnosis as well. Parents who therefore pursue a diagnosis more aggressively are more likely to get it.

Of course, an infectious agent would also spread through proximity, so they tested this possibility by looking at specific features that should differ. For example, the sociological spread hypothesis predicts that the proximity effect should be greatest at the milder end of the spectrum. More clear cut cases are likely to be diagnosed regardless of parental resources or effort, while milder cases will be highly dependent on these factors. They found that the proximity effect existed only among the milder end of the spectrum, and was absent for more severe children. They also found that the effect obeyed school districts – so proximity across a school district demarcation did not confer increased chance of having an ASD diagnosis. Further, they found that children with an ASD diagnosis had similar referral sources to other ASD children with proximity.

All of this points to the fact that parents obtain information from other parents in their neighborhood about which doctors to see, what questions to ask, and how to interface with the school system most effectively to obtain an ASD diagnosis and the increased services that come with it.

Conclusion

This study adds powerful evidence to the conclusion that the increasing incidence of autism is largely due to sociological factors rather than a true increase in the incidence of autism. This does not rule out a true increase also hiding in the data, but rather demonstrates that sociological factors are a significant contributor. This study must also be put into the context of the many other studies supporting the conclusion that the dramatic increase in ASD is due largely to increased surveillance and expanded diagnosis.

I was also not previously aware of the extent of the effect that social stigma has played. Previously parents avoided an autism diagnosis and sought an MR diagnosis, while today the situation is reversed, and the evidence shows the diagnostic substitution we would expect to be the result.

Another prediction of the sociological hypothesis is that eventually autism incidence should level off – once diagnoses are saturated. We are probably getting close to that point now.

All of this also means that scientists are justified in focusing their research efforts on characterizing the genetic risks and causes of ASD. Further, calls for a shift in emphasis to environmental causes based upon the premise that there is an autism epidemic are not valid in light of this research. This does not mean that environmental contributors should not be explored – it is often practical to cover all the bases in medical research – but a significant shift in resources is likely not justified.

I’m sad to say that this is the last day of World Homeopathy Awareness Week.  We’ve tried to give homeopathy its due honor, providing it the attention its practitioners clearly desire, while continuing to cover pertinent news in the world of homeopathy and providing a somewhat more sober, rational discussion of it on our homeopathy reference page.

Of course, most of this has not been news in the literal sense of the word.  There hasn’t been anything truly new in homeopathy since its invention (no, not discovery; discovery implies that something actually exists to be found) by Hahnemann in 1796.

Well, perhaps that’s not quite fair.  As our knowledge of reality (medicine, pharmacology, chemistry, physics, etc) has steadily improved, homeopathy’s plausibility has dwindled to the point of being indistinguishable from the roundest of numbers (0).  And I suppose the recent contortions of logic, abuses of legitimate science, and pure magical thinking put forth to protect homeopathy from the relentless assault of science are far more impressive than that laid out by Hahnemann.  So that’s news of a sort.

There’s also homeopathy’s long and rich tradition of abject failure in randomized controlled trials to consider.  The overwhelming mountain of evidence showing homeopathy to have no effect beyond placebo is impressive and definitive.  That’s data Hahnemann didn’t have, so that’s news too.

Each of these properly conducted studies and analyses demonstrates the scientific method’s utility to help us understand reality and protect us from our own delusions, but frankly, at this point they are about as exciting and useful as proving that the sun will rise in the east tomorrow morning.  News?  Not so much.

Nuremberg’s Less Famous Trial

I found myself wondering how far back this trail of negative trials goes; how long we’ve been having the identical argument.  Pubmed’s earliest mention of homeopathy was in 1906, and the first RCT I found in its database was in 1980.  However, the oldest double-blind RCT of which I found record was conducted in 1835 in Nuremberg, Bavaria, and subsequently described in an editorial in 2006 entitled “Inventing the randomized double-blind trial: The Nuremberg salt test of 1835.” Though the trial has its flaws, it was of sufficient quality to satisfy my historical curiosity with a thoroughly depressing answer: 175 years.

The local physicians and public health officials of Nuremberg held an understandably dim view of homeopathy, and as it gained popularity in Nuremburg they became more vocal, and more public, in their opposition:

Von Hoven accused homeopathy of lacking any scientific foundation. He suggested that homeopathic drugs were not real medicines at all and alleged homeopathic cures were either due to dietetic regimens and the healing powers of nature, or showed the power of belief. He called for an objective, comparative assessment by impartial experts. If, as he expected, homeopathic treatment proved ineffective, the government would need to take drastic measures to protect the lives of deceived patients.”

Sounds familiar, doesn’t it?  Nuremburg’s resident homeopath Karl Prue’s defense should as well:

[Prue] pointed out that even children, lunatics and animals had been successfully cured. Based on Hahnemann’s assertions, he challenged Wahrhold/von Hoven to try the effects of a C30 dilution of salt on himself. The odds were 10 to 1, he claimed, that his opponent would experience some extraordinary sensations as a result – and these were nothing compared to the much stronger effects on the sick.”

Eventually a trial was designed and agreed upon by both parties to test the effect of a 30C dilution of salt.  The trial design was surprisingly good, as it was:

• Randomized: participants had an equal chance of being in either the control or experimental group
• Controlled: participants not given the experimental therapy were given an indistinguishable and inert placebo
• Blinded: participants didn’t know if they received the homeopathic dilution or placebo
• Double-blinded: the experimenters didn’t know which participants received the homeopathic dilution or placebo, as the placebo and homeopathic dilution were prepared and the vials containing them randomized and coded by people independent from the experimenters.
• Well Powered: the trial contained enough participants so that if, as Prue claimed “the odds were 10 to 1… to experience some extraordinary sensations” that it could detect a difference between the two groups.
• Transparent: The design, hypothesis, methods and outcomes were agreed upon beforehand and explained in detail to all participants, conducted publicly (in a literal Pub in fact; these people were full of good ideas), results were published quickly, and any deviation from protocol was acknowledged.

Of the 54 people they managed to enroll, 50 completed the study three weeks later by reporting what, if any, “extraordinary sensations” they had experienced following ingestion of their vial.  5 people reported sensations in the homeopathic group, 3 in the control, which was statistically insignificant.  Homeopathy had failed the first of many RCTs.

I am not putting this trial forward as the final (though perhaps it could be considered one of the first) nail in homeopathy’s coffin.  The trial design had areas of potential bias, most notably that the symptoms which qualified as “extraordinary” are not well defined (though a glance at the homeopathic proving of “Natrum Muriaticum” or “table salt” provides some insight into this particular problem), and the fact that it relied upon participants to honestly report all symptoms; a hostile or imperceptive set of participants could easily confound the study.  Nevertheless, on the whole it was solidly designed and executed, particularly when one considers that this is one of the first double-blind, randomized controlled trials ever documented.

Time To Move On

Here we are in 2010, 175 years after the first of legion negative RCTs of homeopathy, yet it persists with the same tired old arguments.  Is there anything to gain from investing more time, money, resources, and ignoring the highly dubious ethics of subjecting human subjects to a trial that has no hope of benefiting them or humanity, just to prove one more time that homeopathy is an utter failure?  No, and here’s why.

I look at the current debate surrounding homeopathy, and I see three primary groups.  The first accepts the last two centuries of scientific progress and evidence and concludes that homeopathy is a delusion unworthy of further study.  They don’t need another trial.

The second believes in homeopathy in spite of the gargantuan volume of evidence; further evidence will do nothing to change their minds.  They don’t need another trial.

The final group is comprised of people who are unaware of the nature of homeopathy or the evidence that already exists.  This final group requires exposure and education; they require World Homeopathy Awareness Week (SBM edition).  They don’t need another trial.

Michael Specter, author of Denialism: How Irrational Thinking Hinders Scientific Progress, Harms the Planet, and Threatens Our Lives, on the danger of science denial:

Given that more than half of the video is devoted to discussing vaccine denialism, supplements, and HIV/AIDS denialism, I think Spector’s talk is quite appropriate for this blog. Perhaps the best quote in Specter’s entire speech is this: “When you start down the road where belief in magic replaces evidence and science, you end up in a place where you don’t want to be.”

Unfortunately, for more and more of the population, it seems, when it comes to vaccines and “alternative” medicine that’s exactly where they’re going. They don’t want to be there, but unfortunately they won’t realize it until there there. They might not even realize it even then.

Unfortunately, society will.

World Homeopathy Awareness Week is fast coming to an end, unfortunately. And what would any sort of “homeopathy awareness” be without a commentary from James Randi? After all, Steve, Kimball, and I will be seeing Randi on Saturday as we participate in the SBM panel for NECSS:

We at SBM share with Randi his desire that people be aware of the true nature of homeopathy.

On April 2, Steve Novella, Kimball Atwood, and I visited the National Center for Complementary and Alternative Medicine (NCCAM) to meet with its director, Dr. Josephine Briggs. I’m not going to rehash what was said because we agreed that Steve would handle that task, and he did so admirably last week. I agree with Steve that it was encouraging that Dr. Briggs apparently reads this blog and shares many of our concerns about NCCAM, the poor science that it has funded, and its use by promoters of unscientific medicine to promote their quackery. Most heartening of all was that she appeared to recognize how much CAM is infused with anti-vaccine beliefs and, worse, the promotion of these beliefs to the detriment of public health.

Those positive reactions to what was a friendly but frank exchange of views notwithstanding, as we were sitting in a conference room next to Dr. Briggs’ office, I couldn’t help but wonder what the reaction of CAM promoters would be when they found out about this meeting. Now I know. John Weeks over at The Integrator Blog is not happy:

Novella’s posting reads like a Fox News interview: 95% his team’s point, then a brief NCCAM response. That Briggs asked for the meeting likely grew out of an early March conference at Yale at which Novella and she both participated. For this, she deserves the Barack Obama Big Tent award for her proven interest in sitting down with everyone, no matter which party affiliation or belief. (Some have said this was proven in early 2008 when Briggs met with me.) Arguably, Briggs takes her openness to dialogue further than the President. While Obama has kept arms length from leaders who call for the demise of the United States, Briggs has now met with those who have been lobbing bombs at her professional home for years, calling steadily for NCCAM’s destruction.

Because our previous calls for the closing of a relatively small government institute because we view it as a poor use of taxpayer money is just like calling for the downfall of the United States government. Weeks clearly likes ridiculously overblown hyperbole. Interestingly enough, what appeared to upset Mr. Weeks the most was our discussion of homeopathy with Dr. Briggs. As Steve put it:

Dr. Briggs pointed out that it is not the job of the NCCAM to make final pronouncements about any treatment or medical claim. This is fair enough — but depends on context. The NCCAM is responsible for informing the public about so-called CAM modalities, and that should include a fair assessment of the science. If the science says a treatment is worthless, the NCCAM should not be afraid to say so.

Further, the NCCAM does determine what studies the NCCAM funds. The NCCAM accepts applications for research into homeopathy, but have not funded any in several years. What does this mean? Will they consider funding homeopathy research, and if so they are basically saying that they do not close the door on any medical modality, no matter how implausible or damned by negative evidence.

If they will not consider funding homeopathy, then why are they accepting grant applications for homeopathy research? This could be construed as disingenuous — perhaps a way to not fund homeopathy research without having to say they will not fund homeopathy research.

Steve is correct. The NIH can never totally close the door on any line of research. It can, however, set priorities. It could decide that, given the homeopathically diluted prior plausibility of homeopathy based solely on physics, chemistry, and biology, homeopathy is not a priority. It can make sure that only reviewers with the relevant background in basic and clinical science — not “homeopathic” science — make up the study sections that review NCCAM grants. Indeed, I was much heartened to learn from Dr. Briggs that she had already moved peer review of CAM grants out of NCCAM-sponsored study sections and into regular standing NIH study sections run by the Center for Scientific Review, which is where the vast majority of NIH grants are normally reviewed.

As a sort of counterpoint to our message, Mr. Weeks described in the same post a meeting that Dr. Briggs had with an “international homeopathic team.” Besides the amusement I felt at the word choice (is a homeopathic team a team so diluted that there is no one there?), the content itself was at the same time both disturbing and full of hilarious howlers. For instance, this passage concludes the section discussing our visit:

That said, what would have been especially interesting is if Briggs’ scheduler crossed wires and the anti-NCCAM bloggers and homeopathic researchers had showed up for the same meeting time.

I can’t speak for Steve or Kimball, but I assure Mr. Weeks, that I probably would have enjoyed such an encounter thoroughly, although we would have been disappointed that we wouldn’t have been able to have the discussion that we had planned on.

But how did the meeting between Dr. Briggs and the homeopaths go? This is how Mr. Weeks describes it:

Gahles, in a report to the Integrator, assessed that the meeting went “very well.” In her view, a presentation by Chaplin and Roy on chemistry and slides that “showed activity of homeopathic remedies on basophils and IgG” seemed to be particularly compelling to the NCCAM team in suggesting mechanism of action. Gahles underscored that conventional bio-markers seemed to be key in stimulating interest from the NCCAM team.

On the other hand, a presentation on quantum physics and energy medicine seemed to be less useful in making in the case. At one point, an NCCAM team member who said he found the presentation “powerful” asked what the community of top scientists would think. Those in the meeting responded: “We are the leading scientists in the field.”

More like the leading pseudoscientists in the field. The thought of a homeopath claiming to be a leading scientist, particularly when it comes to physics and energy brings to mind Dr. Charlene Werner’s tortured attempt to explain homeopathy through physics or John Benneth’s attempt to explain it as “nanocrystalloids.” Maybe they’re the “leading scientists” of the field of homeopathy. Or perhaps Mr. Weeks means Dana Ullman. Or maybe Jacques Benveniste. In any case, it’s disturbing that an NCCAM team member apparently found the presentation “powerful.” Anyone who finds the clinical research on homeopathy “powerful” does not understand the true tenets of homeopathy and what pseudoscience they are. Such attitudes will tend to stand in the way of attempts to bring more rigorous science to the study of CAM.

Still, Mr. Weeks has done us an unintentional favor — two, actually. First, he has demonstrated clearly that the CAM community wants its pseudoscience, not rigorous science, to guide NCCAM’s research efforts. This has only reinforced my appreciation of Dr. Briggs’ delicate situation. Every move she makes towards bringing rigorous science to the study of CAM is certain to enrage supporters of the purely pseudoscientific CAM modalities such as homeopathy, reiki, and various “energy healing” modalities that are no better than faith healing under different belief systems than Christianity.

Second, Weeks actually points out the heart of the conflict at the heart of NCCAM. Dr. Briggs is clearly trying to move NCCAM in a direction that we at SBM would approve of, namely towards a more drug discovery-oriented approach towards herbal and botanical remedies and various supplements, as well as the study of exercise and various relaxation techniques. After all, these are the most plausible remedies that fall under the general rubric of CAM, and a pharmacognosy approach is the most likely to yield useful information and scientific advances. But that is not what CAM proponents want. Indeed, they resent this approach, as Weeks demonstrates:

One of the perverse pleasures that comes from the disposition of the NIH to hire NCCAM leaders who have no prior experience in alternative or integrative medicine is to think of the culture shock when they move from a zone of relative comfort — drug research on fractions of botanical — into the far reaches such as homeopathic theory and practice. In truth, forms of energetic thinking and practice are infused throughout the “CAM” universe; homeopathy’s dance with Avogadro’s number merely makes it, with distant prayer, the most challenging.

“Challenging” is putting it mildly. But this is the kicker:

It is probably good that Briggs’ extensive and admirable self-education process over the last 2 years preceded this meeting. The culture shock may had this meeting been in her first months.

I rather suspect that Mr. Weeks is correct here, only not in the way he thinks. I’m willing to bet that it was a major culture shock for Dr. Briggs to find out just how much magical thinking, religion, and pseudoscience underlie so much of CAM. What Weeks calls a “comfort zone” is in reality nothing more than staying within what can be studied and demonstrated scientifically, which is what scientists do. If homeopaths could produce anything more than centuries-old magical thinking to support their quackery, if they could produce actual science in the form of physics, chemistry, and biology to support their mystical beliefs in the “memory” of water and that “like cures like,” then their discipline would enter the realm of science, rather than being relegated to the realm of pseudoscience. The problem, of course, is that homeopathy and the “energy healing” modalities are so removed from science that this is about as unlikely to happen as there is likely to be a single molecule of active remedy left in a 30C dilution.

Therein lies the conflict at the heart of NCCAM, and, although I approve of Dr. Briggs’ attempts to increase the scientific rigor of NCCAM and, given that NCCAM isn’t going anywhere, see that as the best path towards trying to make NCCAM a useful center in the NIH, I’m afraid that her actions will only exacerbate the conflict. It’s the institution and the laws that created it that are the problem, and Dr. Briggs won’t be there forever. Her successor might not be as dedicated to science as she is. (In fact, if people like John Weeks get their way, you can count on it.) No matter how much Dr. Briggs may change the culture of NCCAM under her stewardship, all it takes is a new director to change it right back. Directors come and go, but institutions last for generations.

An article entitled “The Burden of Suboptimal Breastfeeding in the United States: A Pediatric Cost Analysis,” by Bartick and Reinhold, was published in Pediatrics 2010 April 5. According to this news report, it showed that 900 babies’ lives and billions of dollars could be saved every year in the U.S. if we could get 90% of mothers to breastfeed for at least 6 months. It says breastfeeding has been shown to reduce the risk of stomach viruses, ear infections, asthma, juvenile diabetes, Sudden Infant Death Syndrome and even childhood leukemia.

This new study did not provide any new evidence. It simply took risk ratios from a three year old government report, extrapolated, and estimated the costs.

The report it is based on, the 2007 breastfeeding report from the Agency for Healthcare Research and Quality, examined 43 primary studies on infant health outcomes, 43 primary studies of maternal health outcomes, and 29 systematic reviews and meta-analyses that covered some 400 other studies. They found that

a history of breastfeeding was associated with a reduction in the risk of acute otitis media, non-specific gastroenteritis, severe lower respiratory tract infections, atopic dermatitis, asthma (young children), obesity, type 1 and 2 diabetes, childhood leukemia, sudden infant death syndrome (SIDS), and necrotizing enterocolitis.

They found

no relationship between breastfeeding in term infants and cognitive performance. The relationship between breastfeeding and cardiovascular diseases was unclear. Similarly, it was also unclear concerning the relationship between breastfeeding and infant mortality in developed countries.

So how could they take a study that showed no clear relationship with mortality and re-interpret it to predict that 900 lives a year could be saved? They used statistical skullduggery. They went to other statistical sources to find the rates of breastfeeding and the overall death rates from diseases like asthma. Then they used their imagination to estimate how many of these deaths involved non-breastfed children. Then they combined those estimated death rates together with the odds ratios from the AHRQ study to do their calculations. That’s not kosher.

There are other factors to consider. One of the reported adverse effects, necrotizing enterocolitis, is largely a disease of newborns who are premature and have low birth weights. Some of the diseases are treatable and not usually serious, like otitis media. And the risk of otitis in bottle fed babies can be decreased by not letting the child hold the bottle or take it to bed. For some conditions like atopic dermatitis, the risk depends on the family history: in this study  there was an increased risk of atopic dermatitis with breastfeeding when parents had no history of allergies.

It’s interesting to read all the caveats in the text of the AHRQ report, especially about the dangers of relying on systematic reviews and meta-analyses when the individual studies those reviews are based on may be flawed. 80% of the studies included in their analysis were surveyed only via these secondary sources. There are individual studies that contradict their findings for most of the conditions they studied. The report’s conclusion cautioned:

A history of breastfeeding is associated with a reduced risk of many diseases in infants and mothers from developed countries. Because almost all the data in this review were gathered from observational studies, one should not infer causality based on these findings. Also, there is a wide range of quality of the body of evidence across different health outcomes.

That’s not exactly a ringing endorsement of reliable data to base a cost assessment on.

One of the commenters on the news story said

There is no reason for a healthy well-fed mother not to breast feed her baby

I beg to differ. There are a lot of healthy well-fed mothers who have found what they think are valid reasons not to breastfeed. I chose not to breastfeed my babies because it was inconvenient, time-consuming, interfered with my sleep, and was incompatible with my job as a doctor working 24 hour shifts in the emergency room and as a flight surgeon on call. I suppose I could have pumped milk and planned ahead and found a way to do it, but it would have required heroic measures. I can imagine leaking breast milk all over my flight suit when I was on an emergency helicopter mission and simply couldn’t stop to pump. Moreover, I tried breastfeeding briefly with my first baby and frankly, I didn’t like it. All in all, I thought my babies were better off with a happy mother and a bottle.

This new study confirms what we already knew: that breastfeeding is better for a baby than bottle-feeding. The question is how much better, and this study really can’t answer that question. It consists of estimates based on estimates based on mixed data of varying quality. Considering the quality of the data and the pitfalls of epidemiological studies, it is likely that this new study overestimates the value of breastfeeding and the number of preventable deaths.

If we could accurately calculate the numbers needed to treat (NNT) with breastfeeding to save one baby’s life or prevent one ear infection, they would be very high numbers. Mothers should be given those numbers; but they should also understand that if they bottle-feed, the odds are good that their child will thrive.

Breastfeeding is clearly better for babies, and I strongly support it, but I think the facts leave us room to support those women who make an informed choice not to breastfeed. Some women can’t produce enough milk or have health problems that interfere with breastfeeding. Some women know the benefits of breastfeeding but choose not to do it. We may not agree with their choice, but we can respect their autonomy. Thank goodness we now have safe, nutritious infant formulas that give us a choice.

Today, April 10, is the first day of World Homeopathy Awareness Week (WHAW), or, as I like to call it, World Sympathetic Magic Awareness Week. This week long “celebration” runs from today until April 16. Now, given the dim view of homeopathy which, I daresay, each and every blogger here at SBM shares, you’d think I wouldn’t want people to pay attention to WHAW. Nothing could be further from the truth. It is because I view homeopathy as nothing more than quackery based on magical thinking that I actually want people to be aware of it, starting with some of the more amusing bits that homeopaths have published over the last year. Like this bit:

Which Steve discussed here, and Orac had some fun with here. (Steve’s deconstruction of Benneth’s nonsense brought responses calling him a hypocrite, a Nazi or a “slave breaker.”)

Or this bit:

Which Orac also had some fun with here and Steve had a bit of fun with here.

All of which is why this is the best homeopathy poster ever:

In fact, these two videos probably demonstrate the utter ridiculousness of homeopathy better than almost anything else, which is why I present them again in honor of WHAW. First, there’s the already classic Mitchell and Webb sketch, even though it’s maybe a year old:

Then there’s an oldie but goodie, Homeopathic E.R.:

And let’s not forget that stand up comedy can be perfect for deconstructing nonsense like homeopathy:

David Mitchell and Dara O’Briain even talk about it a bit:

There. I trust I’ve done my part to spread awareness of homeopathy in honor of World Homeopathy Awareness Week. But more can be done. For instance, I suggest you peruse the posts in the homeopathy category of this blog. And, don’t forget, there are still six days to go. Here’s hoping we find some more fun to have with homeopaths before next Friday rolls around, after which Steve, Val, John, Kim, and I will see some of you at NECSS the following day!

April is National Autism Awareness Month, and as of today April is nearly half over. Do you notice anything different compared to the last couple of years? I do. Can you guess what it is?

The anti-vaccine movement’s usual suspects haven’t been all over the mainstream media, as they usually are this time every year, often as early as April 1 or even March 31. In fact, over the last couple of years I had come to dread April 1, not because it’s April Fools’ Day (although the things that made me dread that particular day were often indistinguishable from an April Fools’ Day prank, so full of idiocy were they), but rather the expected carpet bombing of the media by the likes of Jenny McCarthy, J.B. Handley, and their ilk showing up on various talk shows to spread their propaganda that vaccines cause autism. For instance, last year Jenny McCarthy and her former boyfriend Jim Carrey showed up on Larry King Live! with Dr. Jerry Kartzinel (her co-author on her latest book of autism quackery) and J.B. Handley, the last of whom even contributed a guest post on Larry King’s blog, in which he touted an incredibly bad, pseudoscientific “study” commissioned by Generation Rescue, which was more like cherry-picked random bits of data twisted together into a pretzel of nonsense, as I described. Around the same time, Jenny McCarthy was interviewed by TIME Magazine, an interview in which she uttered these infamous words:

I do believe sadly it’s going to take some diseases coming back to realize that we need to change and develop vaccines that are safe. If the vaccine companies are not listening to us, it’s their fucking fault that the diseases are coming back. They’re making a product that’s shit. If you give us a safe vaccine, we’ll use it. It shouldn’t be polio versus autism.

Soon after, Generation Rescue created a website called Fourteen Studies, which they promoted hither, thither, and yon. The idea of the website was to attack the main studies that failed to find a link between vaccines and autism and to promote the pseudoscientific studies that anti-vaccinationists like. In 2008, it was pretty much the same — well, worse, even. When she appeared on Larry King Live! with our old “friend,” anti-vaccine pediatrician to the stars, Dr. Jay Gordon, she shouted down real doctors by yelling, “Bullshit!” (behavior trumpeted by Rachel Sklar of the Huffington Post).

This year? Nothing. J.B. Handley seems to be the man who wasn’t there. Well, not quite: it turns out that J.B. Handley has managed to get a little bit of fawning media attention, but just a little bit, in the form of an interview in The Bloomington Alternative entitled J.B. Handley: It’s unequivocal; vaccines hurt some kids. Apparently Mr. Handley has come down quite a bit in the world. Where’s his appearance with Jenny on Larry King Live! this year? Maybe it’s coming in the second half of the month. In the meantime Steven Higgs will have to do as the new mouthpiece for the anti-vaccine movement.

J.B. Handley: Anti-vaccine warrior and Steven Higgs likes it

Regular readers of this blog will be able to spot the misinformation and anti-vaccine propaganda spewed by J.B. Handley in this article. There’s no doubt that Mr. Higgs is very impressed by J.B. from the very beginning of his article, which contains these characterizations of Mr. Handley:

• It’s not like Handley doesn’t understand the vitriol regularly aimed at him by what he routinely calls “the other side.” He is a pointed, straight-talking pain in their asses.
• McCarthy’s presence, Handley said, allows him to “hang out in the cheap seats and opine and write my own stuff and challenge people.” And in that regard, his style doesn’t earn him any props with the vaccines-are-sacrosanct crowd — the AAP, the pharmaceutical companies, and the government officials and researchers they financially support. He’s described their positions as “atomic stupidity” in articles he has written. Moron is a term he uses often, in print and in conversation.
• Even over the telephone from two-thirds of a continent away, J.B. Handley exudes a large personality and supreme confidence in his experiences and conclusions about his son’s autism.

“Atomic stupidity” describes a lot of what Mr. Handley says on a routine basis, although those of us who’ve butted heads with him in the past tend to refer to it as “burning stupid.” My sarcasm and intense dislike for Mr. Handley aside, given that most of it is typical, run-of-the-mill Generation Rescue anti-vaccine nonsense that I and several of my co-bloggers have refuted time and time again, Mr. Higgs’ article might hardly have been worth my notice, much less blogging about, were it not for this passage, in which Higgs swallows whole J.B. Handley’s premature gloating about a post that Steve Novella wrote for SBM in February:

“Dr. Novella’s piece details a recent study published in the Journal of the American Academy of Child and Adolescent Psychiatry titled ‘A Prospective Study of the Emergence of Early Behavioral Signs of Autism’ that tried to figure out when signs of autism first emerge in babies,” Handley wrote. “Ironically, the study Novella references is quite supportive of the theory that autism is caused by the environment and most notably vaccines.”

The March 2010 study compared two groups of children, one at high risk for autism and one at low risk, and noted the onset of symptoms in children who developed autism. It found no difference in the frequency of visual contact, shared smiles and vocalizations at 6 months. The differences, however, “were significant by 12 months of age on most variables.”

In a blog post on the Web site Science-Based Medicine, Novella wrote, “What these results indicate is that clear signs of autism emerge between 6 and 12 months of age.”

Novella concluded that the study disproved a link between autism and vaccines. “Many children are diagnosed between the age of 2 and 3, during the height of the childhood vaccine schedule. This lends itself to the assumption of correlation and causation on the part of some parents.”

In an addendum to the blog, Novella acknowledged that he erred when he wrote that line, but he insisted, “Many parents blame their children’s autism on vaccines they received after the true onset of symptoms.”

While Handley didn’t comment on the addendum in his Age of Autism counterpost, he said the original line made him “shout and laugh at the same time.” Children have received 19 shots by 6 months — 52 percent of the total vaccination schedule — when the study says early symptoms of autism begin to appear.

Of course, Mr. Handley didn’t comment on Steve’s followup post in his Age of Autism post, because Steve showed very clearly that Handley was, as usual, so wrong that he wasn’t even wrong. In essence, J.B. thought he had found a “gotcha” moment and that one erroneous statement that Steve made in his post was in fact an admission by mistake that the anti-vaccine movement is correct to point out a correlation between the peak ages of autistic regression and the height of the vaccine schedule. Steve admitted his error and then went on to describe clearly why his mistake was not evidence in favor of Mr. Handley’s position.

What was particularly interesting about Mr. Handley’s response that Steve didn’t cover was how much it showed that Mr. Handley has been changing his story and shifting the goalposts over the years. In particular, I noticed this paragraph in which J.B. stated:

More importantly, autism is not an event, it’s a process. It is exceptionally rare that I hear the story, “my son was 100% fine, and at 2 years old after one vaccine appointment he lost everything.” I have heard that story, but very rarely.

If Mr. Higgs had dug a little deeper, he might have realized that that’s exactly the sort of story I see time and time again presented by anti-vaccine believers, J.B. included, as “evidence” that vaccines cause autism.” Is this the same J.B. Handley who has touted at least since 2005 how common stories of children declining right after vaccines are? Let’s see, a couple of years ago he complained to the AAP:

Ms. Martin, let me give you a little insight into my world. If I wanted to find parents who had autistic children and who believed their child’s autism was impacted by vaccines, I wouldn’t need to email the nation’s pediatricians hoping I might find one or two. I could just open my window and yell, because these parents are everywhere in my neighborhood and town! Worse, our numbers continue to grow.

You see, not a day goes by without Generation Rescue receiving an email from a new parent who watched their child decline following a vaccination appointment with their pediatrician. While you search for the handful of parents with autistic children who may support immunizations, we can’t respond to emails fast enough from the thousands we hear from who feel vaccines contributed to their child’s autism.

“Not a day goes by …”? To me that sounded very much as though Handley was arguing that regression after vaccination is very common. Let’s look a bit more, say, from a post JB wrote before going on Larry King Live! last April:

Finally, we have tens of thousands of case reports of parents reporting that their child developmentally regressed, stopped talking, and was later diagnosed with autism after a vaccine appointment. The number of vaccines have risen along with autism rates, vaccines are known to cause brain damage, and parents report regression and later autism after getting them. Is it really so hard to believe we think vaccines are a trigger?

Wow. Tens of thousands of case reports! It appears to me that in his response to Steve there was more than a little bit of goalpost shifting. After all, the “stereotypical” (or “prototypical”) story of the anti-vaccine movement is of the child between the ages of 1 and 3 who is brought to the pediatrician, receives vaccines. Shortly thereafter, or so the story goes, the child loses language and social skills and develops regressive autism. Never mind that, given the number of children who are vaccinated every year and the number of children who develop regressive autism, there are bound to be overlaps such that by random chance alone there will be many children who regress in reasonably close temporal proximity to vaccination. Never mind that no one has ever shown that this regression occurs more frequently in vaccinated children. Anecdotes like the ones JB was touting up until (apparently) now are the very “evidence” that the anti-vaccine movement uses to blame vaccination for autism. And, in all fairness, in a single child not studied in the context of populations, such an event can look all the world as though the vaccine caused the regression even when it did not. Even so, the point is that parents who believe vaccines caused their children’s autism don’t blame a process. They blame vaccines, often specific vaccines like the MMR.

In response to this article, I wrote Mr. Higgs an e-mail. I’ll admit that my tone was a bit peeved. However, it does bother me whenever a journalist give credence to the words of a man who, in addition to having a six or seven year history of spreading pseudoscience fueled by his unrelenting hostility towards vaccines, quite recently publicly gloated that he and his anti-vaccine movement were “early to middle stages of bringing the U.S. vaccine program to its knees.” My e-mail ultimately led to a three-way e-mail exchange between Mr. Higgs, Steve, and myself, and this led me to the definite conclusion that we have a budding Dan Olmsted on our hands.

Who is Dan Olmsted and why doesn’t any reporter want to be like him? Olmsted is currently a regular blogger at Generation Rescue’s anti-vaccine propaganda blog Age of Autism, where he is listed as the editor. What people who haven’t been following this issue a long time is that Olmsted used to be an investigative reporter and senior editor for United Press International (UPI). Between January 2005 and July 2007, Olmsted wrote a series of “investigative” reports in a series that he called Age of Autism (his first installment predating the Age of Autism blog by nearly three years). In the series, he totally bought into vaccine-autism pseudoscience and presented the conspiracy theory through a combination of the same logical fallacies and bad science that undergirds the anti-vaccine movement, including confusing correlation with causation to blame thimerosal in vaccines or vaccines themselves for autism.

Olmsted’s most infamous gaffe was to be, as far as I can tell, the originator of the myth that the Amish don’t vaccinate and that as a consequence they don’t get autism, a fallacy that Olmsted first reported in a two-part story entitled The Amish Anomaly (Part 2 here) and revisited time and time again. Of course, the Amish do vaccinate and there are autistic Amish and Olmsted missed a clinic in the heart of Amish country that treats autistic Amish children, but facts didn’t stand in the way of a good myth, which has only grown in the five years since Olmsted first imagined it.

Ultimately, Dan Olmsted left UPI (whether he resigned or was fired, only he and UPI know) and is now the editor of the anti-vaccine crank blog Age of Autism, where he can “report” to his heart’s content, free of any pesky concerns about editors insisting on actual facts and science. Steven Higgs looks as though he’s ready to join him.

An anti-vaccine reporter

Unfortunately, when it comes to autism and vaccines, it’s not that uncommon for reporters to fall for the myth. The reasons aren’t hard to understand. If there’s one way for a reporter to establish a name for himself, it’s to uncover a big story, the bigger the better. One category of story that is particularly seductive is the huge health scare, particularly if it’s something seemingly benign that is causing it.

Something like vaccines.

Higgs certainly isn’t the first. After all, David Kirby was seduced by the idea that mercury in the thimerosal preservative that used to be in vaccines was the cause of autism. After he published Evidence of Harm: Mercury in Vaccines and the Autism Epidemic: A Medical Controversy in 2004, whatever remained of his journalistic career went into the crapper, leaving him to blog for The Huffington Post and, of course, Age of Autism. Then there’s a local connection, Steve Wilson, who up until recently was an investigative reporter for a local television station here in Detroit and who also bought into the myth that mercury in vaccines causes autism, a report that I duly criticized him for, even though I did it with some trepidation. My cancer center has a good relationship with the TV station that Wilson used to work for, and I was concerned that I would catch some flak for criticizing his report, which was nothing more than a rehash of the standard anti-vaccine mercury fear mongering. The sad thing is that Wilson did some absolutely outstanding work uncovering the malfeasance of our former mayor Kwame Kilpatrick. Unfortunately, his skepticism when it came to vaccines was in reality a pseudoskepticism, showing that even good investigative reporters can be crappy science and medical reporters.

Whether Higgs has any redeeming qualities in terms of investigative reporting skills, I don’t know. What I do know is that he has thoroughly drunk the Kool Aid, as demonstrated in spades in a story he published a month ago entitled Do Vaccines Cause Autism? In it, he tries to refute a contention by Dr. Phil Landrigan in a recent paper in which Dr. Landrigan stated bluntly (and correctly): “There is no credible evidence that vaccines cause autism.” In the article, Higgs repeated a number of common anti-vaccine tropes, tropes so common that I don’t feel obligated to answer them all, given that virtually all of them have been discussed before right here on this very blog. Some of them are talking points straight from Generation Rescue. For example:

• Higgs confuses correlation with causation when it comes to thimerosal. Unfortunately, there is a lot of evidence showing no correlation between thimerosal-containing vaccines and autism. The idea that thimerosal in vaccines cause autism is a failed hypothesis. It’s been tested scientifically and failed.
• Higgs buys the Generation Rescue line that nations with higher vaccination rates have higher autism rates and that vaccination does not correlate with lower childhood mortality. This is about as bogus a study as I can imagine, incompetently performed using cherry-picked data and not even peer-reviewed.
• Higgs cherry picks conclusions from a study of thimerosal-containing vaccines and neurodevelopmental disorders other than autism. That particular study produced results that were entirely consistent with random chance correlations from multiple comparisons. Indeed, if Higgs takes the negative correlations seriously, one wonders why he didn’t mention the positive correlations, where children receiving thimerosal-containing vaccines actually had better measurements of neurodevelopmental outcomes. In essence, Higgs cherry picks the bad results and ignores the good results when a careful reading of the study shows that, overall, the effects were consistent with random chance.

I could go on, citing more articles by Mr. Higgs and more refutations of the anti-vaccine talking points that he parrots, but I think you get the idea. If you don’t, I’ll cite Mr. Higgs’ own words:

I’ve spent most of the past 28 years journalistically investigating conflicts between environmental victims and experts in the relevant fields. And, I can say without qualification, the victims have been right and the experts wrong in every significant story I’ve covered. I can’t think of a single exception.

And with respect to vaccines and autism, I say again, without reservation, parents like J.B. Handley and grandparents like Dan Burton are right about vaccines and autism. The experts are wrong, and their behaviors — their vitriolic attacks upon those who disagree, their underhanded political tactics — suggest they know they were wrong.

A closed mind

In my correspondence with Mr. Higgs, to which Steve Novella contributed, I came to the distinct impression that Mr. Higgs had come to view himself as a crusader. His experience with previous environmental catastrophes and the reactions of companies responsible for them has led him to the point where he cannot imagine that a charge like the claim that thimerosal in vaccines causes autism can possibly be wrong. He has become anti-expert and anti-intellectual. Indeed, Steve Novella called Higgs out on his anti-intellectualism, and, incredibly, Higgs’ response was that had lived in a college town for many years around intellectuals and therefore couldn’t possibly be anti-science or anti-intellectual.

But he is.

As a final example, I will mention two things Higgs cited. First, he cited this video as “the most persuasive evidence I have found thus far” and the one moment in time when he came to believe that vaccine cause autism:

Yes, that’s Bernadine Healy, former director of the NIH. Unfortunately, in recent years, she’s been flirting with the anti-vaccine movement, blaming the American Academy of Pediatrics, the CDC, and other health organizations and “just asking questions” about whether there is a connection between vaccines and autism. She’s also been promoting the idea of a “vaccinated versus unvaccinated” study, apparently not realizing the inherent difficulties involved in such a study. In essence, Dr. Healy, despite her previous position as NIH director (a position she was arguably unqualified for), is not an authority on vaccines. In fact, if you want an idea of how far down the rabbit hole of anti-vaccine lunacy Dr. Healy’s gone, consider that she was named as Age of Autism’s Person of the Year for 2008. If there’s one virtually completely reliable indication that a scientist or physician is well on the way to becoming an antivaccine crank (or has already become one), it’s being named Person of the Year by Age of Autism. It’s like the Nobel Prize, Oscars, Pulitzer Prizes, and Congressional Medal of Freedom for antivaccine crankery and autism quackery all rolled into one.

Finally, Mr. Higgs cited an article entitled Educating the Ohio Valley’s special kids. The interesting thing is that nothing in this article mentions vaccines as a cause of autism. Rather, the entire focus of the article appears to be on mercury and industrial pollution, the argument being that it is that that is correlated with the steadily increasing special education rolls in Evanston, IL. However, in his penultimate e-mail to me, Higgs cited this article and asked:

Related to the thimerosal discussion in “Vaccines and Autism” post, the precipitous rise in the special ed population in Evansville peaked in 2006 and began falling in 07. Using 2002 as the marker for the reduction in thimerosal-laden vaccines for the sake of argument, kids born in that year started kindergarten in 2007. Statewide the trend is the same, thought the decline in special ed population began in 06, but of course thimerosal started coming out before 02. I understand that two years does not constitute a long-term trend, but what other constant do you think every child in Indiana may have experienced in 2002 and 2003, other than vaccines?

I decided to look at the numbers. I was assisted by some blog buddies of mine, including Liz Ditz, who pointed out that a large number of factors could account for such an increase in special ed numbers and a leveling off in 2007, including the starting of campaigns to identify learning disabilities and their eventual leveling off and the effect of funding incentives on special ed enrollment. Multiple people pointed out to me that this leveling off of special ed cases appears to be occurring among all age cohorts. If thimerosal had anything to do with a leveling off in special ed case loads, it should have a far more profound effect in the youngest groups. It didn’t.

Meanwhile, Joseph was kind enough to provide me with a spreadsheet based on actual data, with special education counts for Indiana coming from here and whole-population enrollment counts coming from the National Center for Education Statistics here. He produced for me four graphs.

The first graph shows all disabilities for children aged 6 to 21:

Not much of a change over the period covered, is there? Next, we have a graph of all disabilities in the age group that would be most likely to be affected; that is, if thimerosal had anything to do with developmental disabilities requiring special ed:

Then we have a the same graph for the age group between ages 12 and 17.

Note how it looks very similar to the graph for ages 3-5. If thimerosal had anything to do with diagnoses leading to enrollment in special ed programs, you would expect to see a huge difference between the 3-5 year age cohort and the teenage cohort.

Finally, let’s look at the graph for diagnoses of autism at age 6:

Nope. No sign of a decrease in autism diagnoses in 2006 or later, which is what would be expected if thimerosal, which was removed from most childhood vaccines in late 2001, were a major etiological factor in autism. We can conclude from these graphs that Mr. Higgs is either very naive when it comes to data analysis or he saw what he wanted to see and stopped looking.

Another Dan Olmsted?

Although admittedly I started out trying to address Mr. Higgs with a bit more “insolence” than might have been advisable, I had a hard time restraining myself, given his swallowing of everything that J. B. Handley lays down and his falling for everything Handley says about Dr. Novella. In any case, I tried to be less “insolent” as the correspondence continued. It nonetheless became clear in our correspondence that Mr. Higgs is a true believer, who really does think that Andrew Wakefield has been unjustly abused by the medical establishement and, amazingly, that J. B. Handley knows what he is talking about. I tried to plant a seed by providing him with a number of links, both from SBM and elsewhere, that refuted key points of the anti-vaccine movement. In his responses, he pointedly called me “Mr.” Gorski, even though he knew I am a physician, an intentional bit of disrespect that amuses me more than offends me, given how often I’ve seen anti-vaccine advocates and alt-med practitioners use it. In that, if anything, Mr. Higgs appears less polite than the journalist whose path he seems to be following, Dan Olmsted, or maybe David Kirby, given his fawning three part series interviewing Kirby.

But why?

In Mr. Higgs’ case, I rather suspect that it is really a case of being a true believer. According to him, every environmental health threat he’s seen was accompanied by industry denials and coverups. That may well be true. However, that history has apparently led Mr. Higgs to be so distrustful of what the government and medical authorities say, so suspicious of what “experts” say, that he can’t even consider the possibility that, in the case of vaccines, the experts are actually correct. There is no link between vaccines and autism that science has been able to detect. As passionate as Mr. Higgs may be about environmental pollution, he is, quite simply, on the wrong side of this particular issue and well on the way to becoming another Dan Olmsted supporting the quackery that is DAN!.

Indiana deserves better.

As I pointed out yesterday, World Homeopathy Awareness Week began yesterday. One common question that’s asked about homeopathy goes something like this: If homeopathy is just water, then what’s the harm?

Here’s the harm:

Part 1

Part 2

Homeopathy is magical thinking, far more religious or superstitious in nature than medical or scientific. And this form of magical thinking can lead people people to eschew effective medical therapy, with tragic results.

In a previous post I described a lecture given by a faculty member to first-year medical students on my campus introducing us to integrative medicine (IM). Here I describe his lecture to the second-year class on legal and ethical aspects of complementary and alternative medicine (CAM).

Dr. P began his lecture by describing CAM using the now-familiar NCCAM classification. He gave the NCCAM definition of CAM as “a group of diverse medical and healthcare systems, practices, and products that are not presently considered to be part of conventional medicine.” To illustrate how this definition can lead to surprises, he asked us if the therapeutic use of maggots is CAM or conventional. Although it sounds rather CAM-ish, maggot therapy is used at some surgical centers for wound debridement, he told us, and therefore is part of “conventional medicine.”

I continue to be surprised that thoughtful fans of CAM use this garbage pail definition (anything that doesn’t fit into conventional medicine), because it means that (1) no quackery can be easily excluded from the CAM tent and (2) the only common thread among the sundry modalities is a lack of acceptance from the mainstream medical community. One of Dr. P’s case studies of ethical challenges in CAM use involved a patient’s family that insisted on treating his persistent vegetative state with hyperbaric oxygen therapy — the utility of which Dr. P was highly doubtful — and later Dr. P mentioned intravenous chelation therapy as an example of a CAM treatment that he considered high-risk (compared to, say, parsley supplements). However, both hyperbaric oxygen and IV chelation have uncontroversial indications. Why are they called CAM when used in certain diseases? Presumably only because they are so poorly supported or implausible in those contexts as to be shunned by the medical community, the same community that apparently has adopted as weird (dare I say, unconventional) a therapy as maggot debridement. That maggots won acceptance leads me to be a priori skeptical of any therapy currently defined as CAM, particularly an old one (it still hasn’t been proven). Dr. P appears more optimistic than I, because he seems to interpret the same story as a reason to stay open-minded about most CAM therapies (it still might be proven).

Like the last time, Dr. P stressed that advocacy for use of CAM/IM was not a goal of his lecture. I infer from many of the points and tangential comments he made throughout the lecture, however, that he has a goal of normalizing CAM/IM for us. A frequent refrain was that some ethical precept or legal consideration regarding CAM use was “just the same” as for conventional medicine. Often I agreed with him — all therapeutic options should meet the same standards of efficacy and safety, and many ethical or legal concerns are common for either conventional or alternative approaches — but some of his comparisons seemed questionable:

• For example, after acknowledging that “generally recognized as safe” substances may have unexpected side effects when taken as high-dose supplements (he gave the example of ephedra), Dr. P suggested that in many cases the physician can monitor a patient for side effects while using the supplement, just like we do for patients using pharmaceuticals. Outside of a research context, I would argue that most such monitoring is done for previously characterized adverse effects (e.g., known effects of statins or neuroleptics) and as such can be done more effectively and efficiently than screening for unknown reactions from a mystery drug.
• At one point he mentioned that we accept the 10,000 yearly deaths from NSAIDs in exchange for its benefits; again, it seems to me that the benefits of aspirin are well-defined and understood, in contrast to CAM.
• Dr. P also compared use of CAM to off-label use of pharmaceuticals, implying that both practices are, in a sense, unconventional. Is this a fair comparison?
• He further mentioned that some unethical CAM providers may be more concerned about the health of their income stream than the health of their patients, as evidenced by recommending products they sell. He pointed to similar behavior on the “conventional” side with the example of internists giving cosmetic Botox injections to supplement their low reimbursement rates. I thought this was a bizarre example and a completely false analogy; we could argue about appropriateness, but no one is mislead about health benefits of such a procedure.
• Finally, Dr. P talked about how an IM doc would refer patients to qualified CAM practitioners, much like all physicians refer to appropriate specialists when a patient needs care beyond the scope of their practice. He mentioned, for example, that he will refer a patient to a licensed acupuncturist or a credentialed Reiki master if the patient wants those therapies. Professor Edzard Ernst’s infamous quote regarding regulation of CAM comes to mind.

The bulk of the lecture was devoted to how a physician should respond to a patient request for or use of CAM. Dr. P began by asserting that a physician should neither categorically refuse nor automatically agree to cooperate with CAM administration. Each request should be evaluated in terms of risks and benefits, with consideration given to the patient’s beliefs, cultural values, therapeutic goals, and severity of illness. In doing so, physicians should uphold the ethical principles of autonomy, beneficence, non-maleficence, and justice. Dr. P spoke well on enabling patient autonomy, which he said involved correcting misinformation as much as supporting unconventional choices. When a patient comes to Dr. P with a bag of supplements, Dr. P will go through them and ask non-judgmentally for each, “Why do you take this?” He is then able to gently correct misconceptions or guide towards better information sources, and he has more luck paring down the list when he is knowledgeable about and accepting of the ones more likely to be useful. (Glucosamine? Sure, that may help. But I’m not so sure about this shark cartilage.) Beneficence and non-maleficence speak to risk-benefit considerations; here was the line about deaths from NSAIDs. Justice is about societal fairness and access to care. Dr. P expressed frustration that proven CAM interventions like acupuncture for osteoarthritis (he referenced twice a “definitive” study by Brian Berman, discussed on this blog here and here) are often not reimbursed by Medicare.

Dr. P described three important factors to consider when evaluating a patient request for CAM: safety, efficacy, and curability. “Curability” refers to the patient’s clinical state and prognosis. Dr. P recommends greater tolerance for ineffective or even unsafe interventions if the patient is unlikely to suffer ill effects, perhaps due to comatose state or imminent death. He pointed out that physicians often provide interventions at the end of life that are more for the family’s sake than the patient’s, such as futile resuscitation attempts, and the same leeway should be granted for last-ditch CAM efforts when no standard therapies are available. In the aforementioned (real-life) case of the coma patient treated with hyperbaric oxygen, the family was wealthy enough to easily afford the treatment and was willing to reimburse hospital resources (nursing, ambulance) spent shuttling the patient to and from the hyperbaric quack (for a planned 30+ treatments). As expected, Dr. P spoke eloquently on the need to tease out family dynamics, goals for treatment, unreasonable expectations, etc., and I agree with him that theses thorny ethical issues regarding chronic disease or end-of-life care are independent of CAM use.

On “safety” Dr. P said that CAM (or any) interventions could be classified as proven safe (within reason of course, not in any absolute sense), not proven safe, or proven not safe. He started by telling us that patient’s requests and beliefs never excuse the physician from the professional duty not to harm. Then, with the caveat that some of us may disagree with the following statement, Dr. P read from his slide, “A treatment proven to be safe should be administered out of respect for the patient and/or family autonomy, and to promote an open and cooperative relationship” (my emphasis). Although Dr. P did not mention any such consequence, I believe that this mandate would necessarily lead to physician acceptance of the use of homeopathy and Reiki, even if we all agreed they had no specific efficacy. In my opinion, a more broad-based (dare I say, holistic) consideration of adverse effects of CAM may instead conclude that physicians have a professional and societal responsibility to discourage magical thinking… As for interventions “not proven safe,” here is where Dr. P suggested that cautious use with careful monitoring was appropriate (see my third paragraph). Interventions that are “proven not safe” should be avoided except as allowed by issues of “curability” (previous paragraph).

On the slide for “efficacy” that described the requirement for physicians to “do good” in addition to “do no harm,” Dr. P read a statement that made me sit up with interest: “However, providing some CAM modalities, though not scientifically validated, may have significant benefits for patients by reason of the placebo effect or by improving psychological well-being by demonstrating concern and regard for the patients’ and/or families’ wishes.” But he immediately said that although he included this argument for completeness, he does not actually agree with it; when he uses or recommends a piece of CAM, it is because he truly believes it may have specific benefits. One factor that influences his beliefs and clinical decision making, he next mentioned, is personal experience with a CAM therapy. I must quote him directly: “if I’ve recommended glucosamine 20 times for my patients or 200 times and I’ve seen some benefit, even if a study comes out saying it may not work, that may not change how I’m practicing.” He commented that one can always find flaws in any study’s design (I agree), that one’s biases influence this critical analysis (I agree), and that only rarely does a single article change one’s practice (I agree). Where it seems we disagree is on the value of a single clinician’s uncontrolled observations; I tend to think that such data is hopelessly flawed compared to a consensus view based on the totality of scientific evidence.

Frustratingly, Dr. P segued from this interesting epistemological point to the banal assertion of the importance of listening to patients and engaging in a therapeutic relationship that may lead to healing, not just curing. The next slide implored us to administer any therapy that is proven effective “regardless of its origins.” Again, the maggot story tells me that this is done, but Dr. P seems to feel that CAM is often given short shrift. For example, although several studies have shown efficacy of glucosamine for osteoarthritis (he asserted that many rheumatologists both prescribe and personally use it), Dr. P was annoyed to read press reports of one particular study (GAIT, I presume) that described a limited effect of glucosamine without mentioning that Celebrex had similarly poor effects in some of the study groups. I guess we also agree that mainstream media reporting on science is often misleading!

Dispersed through the lecture were presentations of three cases that illustrated ethical challenges surrounding CAM use: hyperbaric oxygen for a comatose patient, a mother of five who insisted on only alternative therapies for early-stage breast cancer (he tried everything, even called a psychiatrist, to convince her to accept definitive treatment but she refused), and a terminal leukemia patient who asked his advice on an absurd alt-med regimen (massive supplement use, coffee enemas). He stressed that these three patients, like sensational public reports of chemotherapy refuseniks, are very rare exceptions and that the vast majority of his patients use CAM as a safe complement to standard care.

The discussion of legal implications was brief. In Charell v. Gonzalez, a New York court found that “no practitioner of alternative medicine could prevail…as…the term ‘non-convention’ may well necessitate a finding that the doctor who practices such medicine deviates from ‘accepted’ medical standards.” (Interestingly, Dr. P called Gonzalez a “famous” physician and mentioned that after this case he won an NIH grant for a large trial of his anticancer regimen. As of November 2009, Dr. P apparently had not yet heard about the disastrous conclusion of that trial, made public in August 2009 and described here and here.) In Schneider v. Revici, another cancer quack was exonerated because the patient had signed a detailed consent form that marked an “expressed assumption of risk.” Dr. P pointed out that CAM providers are very rarely sued because they tend to have very good relationships with patients. For protection against malpractice charges when using CAM (or any) therapies, he recommended meticulous documentation, clear communication, and a willingness to apologize for failures.

The lecture ended with a touching story about how the husband of the terminal leukemia patient (who went to the Revici clinic against Dr. P’s advice) came back to visit Dr. P after his wife’s death. The husband thanked Dr. P for talking with them frankly and compassionately about their goals and expectations for her final months.

Much of this talk, like the previous one, must have seemed attractive and reasonable to the student with no more than a passing interest in CAM. However, few details were directly relevant to the ultimate question, “Do particular CAM therapies have specific effects?” I am intrigued by how often Dr. P and I agree, such as when he suggested that selection bias may help account for success stories from heroic alternative cancer regimens (i.e., only healthy patients can tolerate them). But if I watch carefully and dig deeply I can pick out issues of contention between us. The forums where we might argue over the evidence for this or that indication, or have the general discussion about interpretation of evidence, are the elective CAM courses presumably attended only by the enthusiastic. Most of my classmates get little more than the vague and rosy exposure that I describe here and here, and in one more future post on third year. I fear that these lectures, while making CAM/IM more palatable, do not adequately equip students for critical analysis of unusual claims.

There have been, in the last 20 years, natural, or perhaps unnatural,  experiments that have helped shed light on the efficacy of vaccines.  Many societies, for reason of political unrest, religion, or a lack of understanding of science and medicine have seen the rates of vaccination decline and with that decline, an increase in the cases of vaccine preventable diseases

Infectious disease spread in populations is not simple.  Hygiene, nutrition, access to health care, and education all play a role in the spread of communicable diseases.  Vaccines have been critical in driving the rates of vaccine preventable illnesses to almost zero, but they are not the only intervention in our armamentarium.

The Soviet Experience.

When the Soviet Union fell apart in the 1980’s, its medical system followed.  Some totalitarian states have been especially good at getting their populations vaccinated.  However, after the fall of Communism, the vaccination rates declined and the diseases they prevented surged.

“...Diphtheria morbidity in Moscow in 1958-1999 are presented. The last epidemic which started at the end of the 1980s and reached its peak in 1994, giving a 59-fold rise in morbidity in comparison with the pre-epidemic period, is characterized in detail. During the epidemic 12,267 persons fell ill, 454 of them died (mortality rate was 4%). Having started in Moscow, the epidemic gradually spread not only over the territory of Russia, but also over some other republics of the former Soviet Union (Ukraine, Belarus, etc.). Possible causes of this epidemic emergency are considered. The ever increasing share of adult population among persons affected by the epidemic (75%) is noted. The infection adults is characterized by severity of clinical manifestations and increased morbidity among adults, is shown. Under complicated social and economic conditions (crisis situation) the increase of groups of high risk which included unemployed adults of working age, retirees as well as socially non-adapted persons, was registered.”

“The massive diphtheria epidemic in the former Soviet Union provides important lessons for all diphtheria immunization programs: It is important to achieve a high level of childhood immunization, maintain immunity against diphtheria in older age groups, and use anti-epidemic measures, including immunization, to control epidemics in the early phase. The immunization coverage among children should be at least 90%.”

“Failure to achieve high levels of immunity among children contributed to the epidemic of diphtheria that occurred in the Russian Federation during the 1990s. A major factor in this failure was the extensive list of contraindications to vaccination that was in use throughout the countries of the former Soviet Union. In 1980, the Ministry of Health (MOH) of the Soviet Union adopted an extensive list of contraindications for use of the diphtheria-tetanus toxoids-pertussis (DTP) vaccine. In 1994, the MOH of the Russian Federation revised the list of contraindications to vaccination to be largely in accord with World Health Organization recommendations. Since then, age-appropriate vaccination coverage has increased markedly: In 1996, DTP3 coverage among children 12 months of age had increased to 87% from 60% in 1990. ”

In the end the only way diphtheria came under control was by increasing vaccination rates.

Similar problems were seen with pertussis.

“The aim of the current study was to assess the epidemiological situation concerning the emergence of a pertussis outbreak, as well as potential contributing factors and vaccine effectiveness. A retrospective epidemiological description and an analysis of the outbreak among students were performed. The basic school in Adavere had a total of 150 students in 2003. Of these, 54 cases of pertussis, with median age 12 y, all corresponding to clinical case definition, were identified with an attack rate of 36%. Regarding confirmation of the diagnosis, out of all clinical cases, 18 were confirmed by laboratory testing (2 by isolation of B. pertussis and 16 serologically based on single sera) and 36 with epidemiological linkage only. Of all the students with pertussis, 35 (65%) had received 4 doses and 6 (11%) 3 doses of DTwP vaccine; 13 (24%) students had received fewer than 3 doses or were unvaccinated. The contributing factors in generating this outbreak were close epidemiological contacts, late identification of pertussis diagnosis in the primary, secondary and later cases, as well as a too late initiated active surveillance. In this outbreak, low vaccine effectiveness and low vaccination coverage also played an important role. ”

As well as rubella and measles outbreaks.

“The data suggest that rubella is endemic in Kyrgyzstan with periodic epidemics every 3-5 years. From January to August 2001, 1936 rubella case-patients were reported from Bishkek City and Chui Oblast; 242 were tested and 176 (73%) were laboratory confirmed. Most case-patients were 3-14 years old. However, the incidence rate per 100,000 among persons aged 15-35 years increased >/=40-fold from 1 in 2000 to 41 in 2001. These findings highlight the importance of introducing rubella-containing vaccine in conjunction with measles elimination activities. ”

While the cause of the outbreaks was multi-factorial, it is interesting how rapidly these infections returned with only a small decline in herd immunity. The control of these diseases was expensive and resource intensive in countries with little economic reserve. These outbreaks represent a subset of the countries that were plagued by vaccine preventable infections after the disintegration of the USSR.  Pubmed (to my mind a verb like google) almost any of the states of the former USSR and you will find other examples of the outbreaks from the decline in the use of vaccines.

Polio

Polio was almost eradicated in Africa.  So close you almost wanted to close down the crutch factories.  Then, in the 2003, religious leaders in Northern Nigeria banned the polio vaccine under the belief that the vaccine was being used as a vector by the West to spread both HIV and sterility, specifically targeting Muslims.  And you thought formaldehyde in the vaccine was bad.

“In northern Nigeria in 2003, the political and religious leaders of Kano, Zamfara, and Kaduna states brought the immunization campaign to a halt by calling on parents not to allow their children to be immunized. These leaders argued that the vaccine could be contaminated with anti-fertility agents (estradiol hormone), HIV, and cancerous agents.”

Even though the ban lasted a mere 11 months, Nigeria saw a resurgence in polio.  Again, we remain at the edge of the infectious precipice and it takes only a tiny push to send people over the edge.    Nigeria also served as a reservoir for polio that subsequently spread to 15 other African countries and beyond.

“After the 1988 World Health Assembly resolution to eradicate poliomyelitis globally,  the number of polio-endemic countries decreased from 125 in 1988 to six (Afghanistan, Egypt, India, Niger, Nigeria, and Pakistan) in 2003 . However, during 2002–2005, a total of 21 previously polio-free countries were affected by importations of wild poliovirus (WPV) type 1 from the six remaining countries (primarily Nigeria) where WPV was endemic.”

Polio is coming under control in Nigeria with increased vaccination, with case falling from 1,129 in 2006 to 285 in 2007. Remember that most children who get ill with the polio virus do not develop clinical polio,  a complication of about 1% of the infections.  So 258 cases represent the tip of the polio iceberg (will this metaphor die in the next 100 years? And if so, what will be the replacement be in a world without icebergs?).

The damage, however, has been done and even though education programs have increased the utilization of the polio vaccine, there are still those who will not let their child receive the vaccine due to fears of contamination with birth control. And this in a society without internet connections.  Fear is much more contagious than infection and harder to prevent or treat. As a result of ongoing fear of vaccines, cases of wild type polio continue in Northern Nigeria with 258 cases in 2009, primarily in the Muslim community.

Most of the world uses the live-attenuated oral polio vaccine as it results in a better response.  The problem with live-attenuated viruses, like any virus, is it likes to mutate when it multiplies.  If the immunity to the virus is high in a population and the hosts are immunologically sound, a live vaccine has no place to go even if it mutates.  It requires non-immune hosts to perpetuate.  Herd immunity keeps any mutated strain at bay.  However, if there are populations whose immune function is compromised by poor nutrition or HIV and there are large numbers of unvaccinated people in the community, then odd things may happen. Vaccine strains can spread.  Because of the perfect storm in Nigeria, the vaccine strain was able to perpetuate in a vulnerable community and now there is a mutated strain of polio vaccine that is causing disease in Nigeria.  The vaccine strain escaped and, thanks to a little evolution, changed to have increased virulence.  This would have been much less likely to occur if the population had maintained their herd immunity.

“The number of polio cases caused by the vaccine has doubled: 124 children have so far been paralyzed, compared to 62 in 2008, out of about 42 million children vaccinated.  There have been at least 7 outbreaks in Nigeria from the vaccine strain.”

The point, and I cannot wait for some of the comments this little factoid will engender (not), is that vaccines work best when everyone participates, and as soon as compliance slips even a little, the replicative and mutational capacity of germs guarantees that they may evolve and escape into the wild.

And even stranger things have happened.

“The biological properties of poxvirus isolates from skin lesions on dairy cows and milkers during recent exanthem episodes in Cantagalo County, Rio de Janeiro State, Brazil, were more like vaccinia virus (VV) than cowpox virus. PCR amplification of the hemagglutinin (HA) gene substantiated the isolate classification as an Old World orthopoxvirus, and alignment of the HA sequences with those of other orthopoxviruses indicated that all the isolates represented a single strain of VV, which we have designated Cantagalo virus (CTGV). HA sequences of the Brazilian smallpox vaccine strain (VV-IOC), used over 20 years ago, and CTGV showed 98.2% identity; phylogeny inference of CTGV, VV-IOC, and 12 VV strains placed VV-IOC and CTGV together in a distinct clade. Viral DNA restriction patterns and protein profiles showed a few differences between VV-IOC and CTGV. Together, the data suggested that CTGV may have derived from VV-IOC by persisting in an indigenous animal(s), accumulating polymorphisms, and now emerging in cattle and milkers as CTGV. CTGV may represent the first case of long-term persistence of vaccinia in the New World”

Of course, the West does not, yet, have a meltdown of the medical-industrial complex nor do we have religious leaders saying vaccines are designed to spread disease and sterility.  Our vaccines cause autism. Hah. Take that Nigeria. Still, we have our own problems with declining vaccination rates.

US  and Great Britain

H. influenzae is killing again.  There have been two mini-outbreaks in the US, one in Minnesota, with five cases and one death and another in Philadelphia, with 6 cases and 2 deaths.  In both outbreaks, the deaths were in unvaccinated children.

Measles has been on the upswing in Great Britain, in large part to a decrease in vaccination.

“The national average (of MMR) in Great Britain is 84 percent, but in some areas of London the vaccination rate hovers at a dangerously low 65 percent. Areas with vaccination rates that are consistently below 80 percent run a high risk of an outbreak.”

There have been over measles 1200 cases in Britain with one death.  At work one of the social workers has been collecting a three word sentence from everyone  that would be your legacy, three words you would want to be remembered by.  I chose “Left them laughing.”  Dr Wakefields may be “Let measles return.”

Measles is back in the US as well.

“During 2008, more measles cases were reported than in any other year since 1997. More than 90% of those infected had not been vaccinated, or their vaccination status was unknown. “

“The number of measles cases reported during January 1–July 31, 2008, is the highest year-to-date since 1996. This increase was not the result of a greater number of imported cases, but was the result of greater viral transmission after importation into the United States, leading to a greater number of importation-associated cases. These importation-associated cases have occurred largely among school-aged children who were eligible for vaccination but whose parents chose not to have them vaccinated.”

Mumps is also making a comeback in the US.  The index case acquired his disease in Great Britain (over 7900 cases) and brought it to the NE, another failure of homeland security.  Since

“January 29, 2010, a total of 1,521 cases had been reported, with onset dates from June 28, 2009, through January 29, 2010, a substantial increase from the 179 cases reported as of October 30, 2009 (1). The outbreak has remained confined primarily to the tradition-observant Jewish community, with <3% of cases occurring among persons outside the community. The largest percentage of cases (61%) has occurred among persons aged 7–18 years, and 76% of the patients are male. Among the patients for whom vaccination status was reported, 88% had received at least 1 dose of mumps-containing vaccine, and 75% had received 2 doses. This is the largest mumps outbreak that has occurred in the United States since 2006.”

Letting vaccination rates decine is associated with increasing disease from vaccine preventable illnesses in part due to a decline in herd immunity.  A recent study in Jama demonstrated the converse: increasing vaccination rates leads to decreased disease in unvaccinated populations.

They vaccinated the children of 25 Hutterite colonies with the influenza vaccine and the children of  another 24 colonies with the hepatitis A vaccine and then looked at the rates of PCR proven influenza in those that did not get the vaccine.  In the influenza group, 39 (3.1%) of those who did not get the vaccine developed influenza while 80 (7.6%) of the unvaccinated in the hepatitis A vaccine groups developed influenza.  This  suggested the overall effectiveness of the influenza vaccine in protecting those who did not get the vaccine, herd immunity, at 60%.  Herd immunity, it seems works. And do let Dr. Jefferson know that the rates of influenza in the influenza colonies was  about half that of the hepatitis A vaccinated colonies.

“Immunizing children and adolescents with inactivated influenza vaccine significantly protected unimmunized residents of rural communities against influenza.”

So vaccines work.  They prevent disease in those who get the vaccine and they can prevent disease those that do not or can not get vaccinated.

Unfortunately, fear of vaccines is increasing in the US .

“Our study indicates that a disturbingly high proportion of parents, > 1 in 5, continue to believe that some vaccines cause autism in otherwise healthy children”

Despite at least 15 studies that show no link between autism and vaccines (except the recent study from Poland that suggested the MMR may protect against autism), the unwarranted fear persists. Irrational fear, as Nigeria has demonstrated, is hard to remove.

If I were convinced that vaccines, despite all the evidence to the contrary,  were the cause of autism or other disease s, and I were to read the that fear of vaccines was up and vaccine use was down, I hope  I would not gloat.  In medicine I am used to bad outcomes occurring as a consequence of what I know to be the correct course of action.  No good deed ever goes unpunished in health care.  I would not be proud that my actions have lead to an increase in morbidity and mortality in children.  I would hope it would be a bittersweet, sad victory, since my success at burning down the vaccine house will take many children with it.  If vaccine rates fall further, some may have the legacy of “Helped plagues return.”

One advantage of having a blog is that I can sometimes tap into the knowledge of my readers to help me out. As many readers know, a few of the SBM bloggers (myself included) will be appearing at the Northeast Conference on Science and Skepticism (NECSS) on Saturday, April 17. Since the topic of our panel discussion is going to be the infiltration of quackademic medicine into medical academia, I thought that now would be a very good time for me to update my list of medical schools and academic medical centers in the U.S. and Canada that have embraced (or at least decided to tolerate) quackademic medicine in their midst. After all, the list is over two years old and hasn’t been updated.

My list is long past due for an update, and I want to post that update right here, either right before or right after NECSS. But I need your help. Please peruse the previous roll of shame. Then either post here in the comments or e-mail to me any examples of quackademic medical programs in the U.S. and Canada (I’ll leave Europe to others better qualified to deal with it) that I may have missed. Equally important, if there are programs I listed before that no longer peddle woo, let me know that too, so that I can investigate and decide if I should remove the program from my list.

I’m particularly interested in the most egregious examples (although your submitting all examples is greatly appreciated). Yoga and meditation don’t bother me that much, for example. Neither do dietary studies, because diet and exercise are science-based medicine that have all too often been coopted by purveyors of woo. Homeopathy and reiki, on the other hand, do bother me. A lot. I’m also particularly interested in educational programs in CAM that are funded by the National Center for Complementary and Alternative Medicine (NCCAM).

Please help me construct the definitive list of academic programs in the U.S. and Canada that have adopted quackademic medicine.

Over the past two plus years of the existence of Science-Based Medicine (SBM) we have been highly critical of the National Center for Complementary and Alternative Medicine (NCCAM) – going so far as to call for it to be abolished. We are collectively concerned that the NCCAM primarily serves as a means for promoting unscientific medicine, and any useful research it funds can be handled by other centers at the NIH.

So we were a bit surprised when the current director of the NCCAM, Josephine Briggs, contacted us directly and asked for a face-to-face meeting to discuss our concerns.

That meeting took place this past Friday, April 2nd. David Gorski, Kimball Atwood and I met with Dr. Briggs, Deputy Director Dr. John Killen, Karin Lohman PhD (Director, Office of Policy, Planning, and Evaluation) and Christy Thomsen (Director, Office of Communications and Public Liaison).

Dr. Briggs very graciously began the meeting by telling us that she and her staff have been reading SBM and they find our arguments to be cogent and serious. She shares many of our concerns, and feels that we are an important voice and are having an impact. She then essentially turned it over to us to discuss our primary concerns regarding the NCCAM.

We were prepared for this.

I first pointed out that many of our concerns deal with issues that are outside the purview of the NCCAM director (such as regulation) and therefore we would not bring them up but would rather stick to constructive feedback and concrete ways in which the NCCAM can better serve its mandate. These issues broke down as follows:

Left to right: David Gorski, John Killen, Steven Novella, Kimball Atwood, Josephine Briggs, Christy Thomsen, Karin Lohman

Ethical Concerns

The NCCAM faces particularly complex ethical issues in funding some clinical trials because of the very nature of the topics it is tasked to research – those with low plausibility that have been bypassed by mainstream research. The ethical guidelines of clinical research dictate that before subjecting a person to an experimental treatment, there is sufficient evidence for safety and plausibility of benefit from pre-clinical and animal studies. It might therefore be considered unethical to subject people to experimental treatments that are highly implausible.

The particular study that is most concerning is the TACT trial, and Kimball reviews the specific details of concern here. TACT is a trial of chelation therapy for heart disease. The concern is that chelation therapy is not a benign treatment and there already has been sufficient evidence to conclude that it does not work. Further study is therefore unethical.

Dr. Briggs acknowledged our concerns, but pointed out two things. First, this study came into being before her tenure at NCCAM (she became director on January 24th 2008). Second, the TACT trial has been turned over to NHLBI (National Heart Lung and Blood Institute), who now sponsors the trial, while the NCCAM still partly funds and collaborates on the trial.

What this means is that Dr. Briggs was able to decline to comment on the TACT trial on the grounds that it falls under the aegis of the NHLBI. This effectively cut off discussion on this topic, which is unfortunate.

This does bring up another issue – the NCCAM funds many studies along with other centers at the NIH, and (as with TACT) they intend to allow centers with the proper expertise to take the lead. NHLBI does heart studies, so they took over TACT. This is reasonable, but does have the consequences of effectively increasing the amount of research funding the NCCAM controls, and also provides cover (intended or not) for controversial studies like TACT.

Kimball intends to follow up with the NHLBI regarding TACT and will likely give us an update.

TACT aside, the ethical concerns remain and this is an issue we will have to follow with future studies.

Types of Studies funded by NCCAM

Another core issue we discussed is the fact that the NCCAM funds many studies that are designed to promote CAM in general or specific CAM modalities rather than study whether or not they are effective. Studying how CAM is used, or barriers to CAM acceptance – prior to demonstrating that any particular CAM modality actually works, is putting the cart before the horse.

But there is a more subtle and insidious problem. So-called pragmatic studies are trials that either compare different treatments or follow outcomes for one treatment in real-world practice. They are often not rigorously blinded nor are variables controlled. They are typically “intention to treat” trials where everyone is followed, regardless of whether or not they complied with the treatment.

Pragmatic studies are a very useful way of tracking real world outcomes. It may be true that aspirin reduces strokes and heart attacks, but what happens when a typical primary care doctor prescribes aspirin? Are their patients compliant? Do they run into side effects or other problems that cause them to stop taking the medication? What do primary docs have to do to improve compliance and minimize side effects? All good questions.

But such studies are simply not designed to answer the question – does aspirin work for the reduction of heart attacks and strokes. Efficacy trials are needed for that.

What we have observed in the CAM world, however, is that pragmatic trials are being performed on treatments that have no proven efficacy, and the outcomes are being misinterpreted and presented as evidence for efficacy. For some modalities, such as acupuncture, this is a very deliberate strategy and is being done in response to well-controlled efficacy trials that are negative.

We would therefore like to see NCCAM focus on efficacy trials, especially for treatments that do not already have proven efficacy. Pragmatic studies of unproven therapies are inappropriate and are ripe for abuse.

Dr. Briggs response on this issue was equivocal – she defended the utility of pragmatic studies but also acknowledged our concerns. We ran into the same problem in that, any examples of such behavior more than 2 years old were before Dr. Briggs time. So we will have to simply monitor things going forward.

Never Say Never

Related to the issue of what kinds of studies the NCCAM should fund is the following question – are there any treatment modalities that have been sufficiently shown to be both implausible and lacking in efficacy that the NCCAM should close the door on future research. When is enough enough?

We used our favorite example – homeopathy, which is especially pertinent following the report of the House of Commons Science and Technology Committee in the UK, who concluded that homeopathy is worthless, cannot possibly work, and should be abandoned in all ways.

It seems to us that the NCCAM (at least so far) has never closed the door on any modality, no matter how implausible and no matter how much evidence for lack of efficacy there is. This seems, if nothing else, like a waste of taxpayer money.

Dr. Briggs response was that in the last two years (under her directorship) the NCCAM has not funded any studies of homeopathy, which is true. However, they still accept applications for homeopathic research, but none have made it through the review process and been awarded funding.

This is a tricky issue. Dr. Briggs pointed out that it is not the job of the NCCAM to make final pronouncements about any treatment or medical claim. This is fair enough – but depends on context. The NCCAM is responsible for informing the public about so-called CAM modalities, and that should include a fair assessment of the science. If the science says a treatment is worthless, the NCCAM should not be afraid to say so.

Further, the NCCAM does determine what studies the NCCAM funds. The NCCAM accepts applications for research into homeopathy, but have not funded any in several years. What does this mean? Will they consider funding homeopathy research, and if so they are basically saying that they do not close the door on any medical modality, no matter how implausible or damned by negative evidence.

If they will not consider funding homeopathy, then why are they accepting grant applications for homeopathy research? This could be construed and disingenuous – perhaps a way to not fund homeopathy research without having to say they will not fund homeopathy research.

This leads directly to our final core point of concern.

NCCAM Information

The final major topic of discussion was the information that the NCCAM provides on its website, newsletter, and press releases. In my opinion this is the easiest problem for the NCCAM to address, and one that is completely and solely within their purview – the information they themselves publish.

We were armed with the latest NCCAM newsletter, in which Dr. Briggs is quoted as saying that “Science must be neutral.” Of course, we agree. But in the same newsletter there is article discussing the evidence for acupuncture and pain showing a model of chi and meridians – mystical life force and the lines through which they allegedly flow.

There is also an interview with a member of the NCCAM national advisory board, Xiaoming Tian, a Chinese Medical Doctor. In the article he states that he uses acupuncture to treat a variety of ailments (1. Chronic and acute pain, 2. Osteoarthritis, 3. Fibromyalgia, 4. Sports injuries, 5. Sciatica and neuralgia, 6. Automobile-accident injuries, 7. Autoimmune diseases, 8. Allergies and asthma, 9. Depression, anxiety, and stress, 10. Bell’s palsy and paralysis, 11. Skin rashes and eczema, 12. Side effects of chemotherapy and radiation therapy for cancer.)

The pattern of information is consistent – NCCAM staff talk about a strict adherence to evidence-based medicine and science being neutral, but interspersed with this is an uncritical presentation of ancient superstition as if it were science, and endorsement of treatments that are not backed by science, and in fact have been shown not to work.

It is my interpretation of the evidence that acupuncture has not been shown to work for any indication (as I have written before, the studies show it does not matter where you stick the needles or if you stick the needles, and any benefit appears to be due to placebo effects, artifact, and the non-specific effects of the ritual surrounding acupuncture – none of which constitute acupuncture itself). But I will acknowledge that there can be some reasonable disagreement about whether or not acupuncture is useful for some symptomatic treatment, like pain. The problem is that wishy-washy evidence for symptomatic benefit is then used to support the use of acupuncture for serious medical conditions, like nerve injury. It’s a classic bait and switch.

All of this confirms our worst fears about NCCAM – that its very existence, and the generally positive and uncritical information it provides to the public, is used to promote and endorse unscientific medical modalities.

In fact, it is not enough to be “neutral”, which could easily fall into the trap of false balance (balancing legitimate scientific evidence and analysis with pseudoscientific promotion). The neutrality of science means letting the chips fall where they may – fairly and honestly reporting the state of the evidence without pulling any punches, like the HCSTC did regarding homeopathy.

But it is my experience that the worst thing that the NCCAM will say about a treatment is that there is not “yet” evidence to support its use. The “yet” is often used, but when not it is implied. Almost invariably the lack of evidence leads to the conclusion that “more research is needed.”  What we don’t hear is that there is evidence for lack of efficacy, or a recommendation to not use a modality or to abandon further research.

Given that the CAM community is actively exploiting the existence of the NCCAM as an imprimatur of legitimacy, the NCCAM needs to take special care to avoid such exploitation. Meanwhile, it seems that they go out of their way to encourage such exploitation (although it seems just out of naivete) or at least make it easy.

We pointed out that we do not expect the NCCAM to engage in “debunking” (that’s our job). But we do expect that they are fair and do not give a free pass or special treatment to a modality because it’s CAM. That is the double standard we are frequently complaining about.

On a side note, Dr. Briggs did agree that anti-vaccine sentiments are common in the world of CAM and that the NCCAM can do more to combat this. Information countering anti-vaccine propaganda would be a welcome addition to the NCCAM site.

Conclusion

We greatly appreciate Dr. Briggs giving us the opportunity to voice our concerns to her and her staff directly. The meeting was overall very pleasant and constructive. We hope this will lead to an ongoing dialogue and as a result we can help the NCCAM evolve into a more science-based institution. Dr. Briggs did clearly voice her intention to make NCCAM a more rigorous scientific institution, in line with other centers at the NIH.

The one concrete result of the meeting was an offer to have experts from SBM review NCCAM material before it is published. We, of course, agreed to offer our services.

There continue to be very important issues and questions that are at a “higher level” than the NCCAM itself – such as the optimal regulation of medical products and practices, and also whether or not the public is best served by having a center of funding at the NIH which is organized around such a nebulous concept as CAM, rather than a disease or biological system. SBM will continue to address these issues head on.

But we are also happy to work with the NCCAM, and Dr. Briggs does profess her intention to move the NCCAM in a more rigorous scientific direction. We will see.

Addendum:

In response to my comment that NCCAM fails to condemn ineffective treatments, the following entry on the NCCAM site was pointed out: http://nccam.nih.gov/health/silver/

In which the NCCAM definitely states that colloidal silver does not work and is not safe. The wording of this entry (noting what the FDA states about colloidal silver) reminded my that Dr. Briggs did specifically mention that the NCCAM information is and will be in line with FDA positions on specific products.

To further clarify my statement – the NCCAM and even some CAM promoters in my experience will at times condemn specific products when there is evidence of harm, such as with colloidal silver. But this does not extend to treatment modalities, like homeopathy, acupuncture, or therapeutic touch, nor to mere lack of efficacy.

Further the threshold for negative conclusions about CAM modalities seems to follow a double standard, otherwise chelation for heart disease would never have made it past a review board.

Science isn’t the only game in town. Literature can teach us things about the world that science can’t. It can give us vicarious experience and insight into other minds. Two recently published novels illuminate why perfectly rational people might reject the help of scientific medicine and prefer to die a little sooner but to die on their own terms.

In Finding Frances, by Janice M. Van Dyck, an elderly woman with COPD and heart disease has had a gradual decrease in her quality of life and has been ready to die for some time. She believes in God and an afterlife and is not afraid of dying. When she needs emergency surgery to remove a section of infarcted bowel, she wants to refuse it, but accepts mainly because she is told that otherwise she will be sent home where insurance won’t cover her care and her husband’s savings will be depleted (which isn’t really true). The first surgery leads to complications and she is offered a second operation with a 25% chance of success. She refuses despite the strong urgings of her health care providers and her entire family. She is given hospice care, stops eating, and eventually dies. The book chronicles the course of the death process in hospice, giving a feel for what the experience is like and how it impacts family members.

In The Leisure Seeker, by Michael Zadoorian, Ella and John, a couple in their 80s, set out on one last road trip in their RV, to follow the entire length of old Route 66 and revisit Disneyland. Their doctors and their children try desperately to dissuade them. He has Alzheimer’s and she has cancer and other health problems: between them they have one functional brain and one functional body. She has refused surgery and chemotherapy, uses a walker, and is dependent on pain pills. He has made her promise that she will never put him in a nursing home. After many mishaps, misunderstandings and misadventures, they manage to reach Disneyland. Then she finds a way to end both their lives at the same time so neither will be left alone. She is a feisty, colorful character and the book is hilarious despite its sad subject. Ella tells us what it feels like to become old and decrepit, to be handicapped and live in pain, and to live with a demented loved one who must constantly be watched and doesn’t always remember who you are. And how one can find joy in the small pleasures of life despite all those problems.

I don’t think I would make the same choices in their situation, but I can understand their choices and empathize with them. They didn’t give up hope or turn to false hopes, but they created their own realistic hope — the hope of a “good death.” They rejected dependence on medical care, took control of their lives, and met death on their own terms. I have to respect their autonomy and admire their courage.

As Ella says at the end of The Leisure Seeker after she plans her own and her husband’s death by carbon monoxide poisoning:

This is not always what love means, but this is what it means for us today. It is not your place to say.

Editor’s note: Three members of the SBM blogging crew had a…very interesting meeting on Friday, one none of us expected, the details of which will be reported later this week–meaning you’d better keep reading this week if you want to find out. (Hint, hint.) However, what that means is that I was away Thursday and Friday; between the trip and the various family gatherings I didn’t have time for one of my usual 4,000 word screeds of fresh material. However, there is something I’ve been meaning to discuss on SBM, and it’s perfect for SBM. Fortunately, I did write something about it elsewhere three years ago. This seems like the perfect time to spiff it up, update it, and republish it. In doing so, I found myself writing far more than I had expected, making it a lot more different from the old post than I had expected, but I guess that’s just me.

In the meantime, the hunt for new bloggers goes on, with some promising results. If we haven’t gotten back to you yet (namely most of you), please be patient. This meeting and the holiday–not to mention my real life job–have interfered with that, too.

The continuum of surgical research in science-based medicine

One of the things about science-based medicine that makes it so fascinating is that it encompasses such a wide variety of modalities that it takes a similarly wide variety of science and scientific techniques to investigate various diseases. Some medical disciplines consist of mainly of problems that are relatively straightforward to study. Don’t get me wrong, though. By “straightforward,” I don’t mean that they’re easy, simply that the experimental design of a clinical trial to test a treatment is fairly easily encompassed by the paradigm of randomized clinical trials. Medical oncology is just one example, where new drugs can be tested in randomized, double-blinded trials against or in addition to the standard of care without having to account for many difficulties that arise from difficulties blinding. We’ve discussed such difficulties before, for instance, in the context of constructing adequate placebos for acupuncture trials. Indeed, this topic is critical to the application of science-based medicine to various “complementary and alternative medicine” modalities, which do not as easily lend themselves to randomized double-blind placebo-controlled trials, although I would hasten to point out that, just because it can be very difficult to do such trials is not an excuse for not doing them. The development of various “sham acupuncture” controls, one of which consisted even of just twirling a toothpick gently poked onto the skin, shows that.

One area of medicine where it is difficult to construct randomized controlled trials is surgery. The reasons are multiple. For one thing, it’s virtually impossible to blind the person doing the surgery to what he or she is doing. One way around that would be to have the surgeons who do the operations not be involved with the postoperative care of the patients at all, while the postoperative team doesn’t know which operation the patient actually got. However, most surgeons would consider this not only undesirable, but downright unethical. At least, I would. Another problem comes when the surgeries are sufficiently different that it is impossible to hide from the patient which operation he got. Moreover, surgery itself has a powerful placebo effect, as has been shown time and time again. Even so, surgical trials are very important and produce important results. For instance, I wrote about two trials for vertebral kyphoplasty for ostoporotic fractures, both of which produced negative results showing kyphoplasty to be no better than placebo. Some surgical trials have been critical to defining a science-based approach to how we treat patients, such as trials showing that survival rates are the same in breast cancer treated with lumpectomy and radiation therapy as they are when the treatment is mastectomy. Still, surgery is a set of disciplines where applying science-based medicine is arguably not as straightforward as it is in many specialties. At times, applying science-based medicine to it can be nearly as difficult as it is to do for various CAM modalities, mainly because of the difficulties in blinding. That’s why I’m always fascinated by strategies by which we as surgeons try to make our discipline more science-based.

Three years ago, I attended a rather fascinating session sponsored by the Society of University Surgeons on surgical research issues involving bioethics and institutional review boards. I realize that there are those out there, particularly on the medical side of things, who with a sneer will refer to the term “surgical research” as an oxymoron, but, trust me on this, there are a lot of surgeons out there trying to do scientifically rigorous studies within the bounds of their discipline to advance the art and science of surgery, all for the good of their patients. (OK, there’s also glory to be had, but the primary motivation still usually boils down to wanting to do good for our patients, with the glory being a secondary motivation.) One other aspect of surgery, besides the ones that I just mentioned, is that surgery is just as much a craft as it is a science. How a surgeon ties knots, where he places the incision and how large he makes it, how he puts together two ends of bowel so that they don’t leak, all of these things are examples where the skill of the individual surgeon matters as much as the scientific validity of what operation the individual surgeon is performing. Surgical research differs from research carried out in medical specialties in that it is much more difficult to standardize operations; placebo controls (i.e., sham operations) are rarely ethically acceptable; and double blind studies are in essence impossible, because the operator will always know what he did and blinding the patient to what was done is similarly impossible without doing sham operations. Moreover, new surgical procedures have a learning curve, such that they may seem less desirable early on in their development but their benefits become apparent the more practice surgeons have at them and as more surgeons learn how to do them well. All of these factors tend to make surgical research, I would argue, in many ways more difficult than medical research, particularly research comparing drug treatments, where double blinding is possible and placebo controls can often be used.

One commonly accepted definition of research is found in federal regulations about human subject research: “Research means a systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalized knowledge.” Innovative surgery is often not systematic. Rather, it is designed to benefit individual patients; there is often no intent to publish the surgical series at a later time, or such intent is secondary. In reality, many, if not most, advances in surgery don’t come from careful controlled trials (at least not at first), and the topic of the conference was how to decide when alterations in an established surgical procedure constitute what was referred to as “tinkering” and when they constitute an “innovation,” which is more substantive (more on this later). And when does a surgeon cross the line from tinkering into innovation into actual human subjects research, anyway? These are actually pretty tough questions, with a lot of complexities involved, and the main impetus for the SUS to undertake a project to try to write guidelines about these issues, the preliminary draft of which were presented at the session I atteneded, was as a pre-emptive strike: To do it first before the government steps in and does it in its typically ham-fisted manner. Also, a lot of this tinkering and innovation go on outside the confines of academic medical centers, out in the “real” world of private practice surgeons. The end result was a position statement published in 2008 in the Journal of the American College of Surgeons entitled, appropriately enough, Responsible Development and Application of Surgical Innovations: A Position Statement of the Society of University Surgeons. It begins:

The field of surgery has a unique culture and rich tradition of innovation. Surgeons are trained to perform continuous situational assessment, decision analysis, and improvisation, in preparation for the challenges and creativity required by nearly every clinical case. Indeed, as Riskin and colleagues point out, “most surgeons innovate on a daily basis, tailoring therapies and operations to the intrinsic uniqueness of every patient and their disease.” In addition, unsolved problems and repetitive failures—or at least suboptimal outcomes—stimulate surgeons to strive for a better way to address challenging surgical problems. Consequently, the practice of surgery is steeped in innovation.

In the United States, development of new drugs and medical devices is closely monitored by the federal government. The Food and Drug Administration (FDA) regulates biologics, devices, and drugs by reviewing their safety and efficacy for a given indication before granting approval for marketing and distribution. The labeling (package insert) summarizes what the FDA has deemed the safe and effective use of the product, and “off-label” use of a product, although allowed, may be subject to regulatory scrutiny.

Such oversight does not necessarily extend to surgical innovations. The surgical innovator has historically been allowed to “tinker” with procedures, introducing modifications of varying degrees to the point that a procedure could arguably be called new. In fact, there are numerous examples of such innovations currently in clinical use, most notably, the myriad variations of minimally invasive procedures. Rapidly advancing technology offers the surgeon a steady stream of opportunities to innovate, and this is encouraged by the incentive to publish or present novel approaches, the need to attract new patient referrals, and the innate desire to improve the quality of care delivered by one’s profession. But there are currently no formal regulations that apply to surgical innovations.

Consequently, the gap between regulatory goals and professional reality is widening. With the importance of ensuring patient safety, it is clear that surgical innovation can no longer enjoy its unmonitored status.

Surgical innovation in itself is not problematic. Indeed, a safer, more effective, or less morbid procedure would have a direct and favorable impact on patients. The absence of any organized oversight or mechanism to protect patients from becoming unwitting research subjects is, however, problematic.

Patients may be harmed by innovations that are less effective or more dangerous than expected. More than a decade ago, Roy and colleagues observed, “When large numbers of innovative treatments are being continuously introduced into clinical practice, rigorous testing is mandatory for the protection of individual patients and the just use of limited resources. This holds true with even greater force in light of the evidence that many innovations show no advantage over existing treatments when they are subjected to properly controlled study.” Concerns about inadequate testing of operations have led to increasing calls for vigilance to prevent cavalier innovations and to ensure scientific evaluation of new procedures.

This last paragraph tells what is so problematic about much surgical “innovation.” For example, as I’ve mentioned before, in the late 1980s and early 1990s, laparoscopic cholecystomy rapidly replaced the open cholecystectomy as the standard of care for gallbladder disease requiring surgical intervention. It did so not based on randomized clinical trials showing it to be superior (or at least not inferior) to the prior “gold standard” operation, but rather because the technology was sexy and it was very satistfying (not to mention attractive to patients) to be able to remove a gallbladder while leaving only a few tiny scars and at the same time being able to send the patient home the same day or the next day, compared to a several-day hospital stay. In essence, marketing won out before science, and science has played catch up ever since. Older surgeons had to learn the new technique or watch their bread-and-butter cases be referred to surgeons who could do the new technique. Moreover, in the early days of laparoscopic cholecystectomy, it was documented that the rate of common bile duct injuries was considerably higher than for the old operation. Given that common bile duct injuries can be devastating, even to the point of leading to liver failure, and that they can require huge operations to repair, sometimes with unsatisfactory results, this was not a problem to dismiss lightly. These days, the rate of common bile duct injury for laparoscopic cholecystectomy is very low, but in the “learning curve” phase of the adoption of the procedure it was not and it is arguably still somewhat higher than it was “in the old days” before laparoscopic cholecystectomy. I’ve also written about other examples of surgical procedures that spread like wildfire before they had been adequately proven through clinical trials. The aforementioned kyphoplasty for ostoporotic vertebral fractures is an example of just such a procedure, as well.

Still, there is a gradation between a modification of an old procedure and a whole new procedure. I’ll illustrate with an example. Sid Schwab described a perfect example of tinkering by a private surgeon when he told how, over time, he developed a “mini-cholecystectomy.” (This was before the days of laparoscopic cholecystectomies.) There was no clinical trial to test his hypothesis that he could do a cholecystectomy through a smaller incision. He just did it, confident that he could always make the incision bigger if he was struggling too much. (It’s an axiom in surgery that you can always make the incision bigger, but you can’t make it smaller.) Clearly this qualifies as “tinkering”; i.e., the minor modification of a surgical procedure that does not produce a reasonable expectation of increased risk to the patient. Of course, if Dr. Schwab were too much of a “cowboy” to admit when he couldn’t do the operation using a the smaller incision and started getting into trouble because he couldn’t see or get his instruments in there adequately, you could imagine that this tinkering might have the potential to cause harm. But Dr. Schwab is a prudent and skilled surgeon; it’s reasonable to trust that his judgment is good and that he’ll do the right thing and make the incision bigger if he finds himself struggling too much. Lots of procedures have been improved by such tinkering, and, in fact, often such tinkering is simply a reflection on the skill of the surgeon; for example, one of my partners can do a right colectomy through what to me is an amazingly small incision, while other surgeons use much bigger incisions to do the same operation.

Basically, it was widely agreed that there is generally no need for IRB involvement when tinkering with surgical procedures, as long as informed consent is given or, if the operation was done emergently, the patient is informed afterwards what was done. In practice, though, I can see this as a bit problematic. Consider Sid in the example above. Suppose he went up to his patient and said, “I’m going to do your cholecystectomy, but I’m going to do it a little different. I’m going to use a small incision. It means I might struggle a bit and the operation may take a little longer, but I can always open wider if I have to.” Most patients wouldn’t object, but many would ask: “How much smaller?” A reasonable question. If the incision is only, say, 5% smaller than the usual incision, would it be necessary to tell the patient? After all, only Sid would know for sure that it was smaller than his usual incision. Other surgeons might make that size incision just from their own training, and even Sid, unless he measures all of his incisions to the millimeter, probably varies his incision size by as much as 5% from patient to patient just in the normal scope of his practice.

So, what is innovation? Innovation differs from research in that it is a change in therapy designed to benefit an individual, whereas research is a study according to protocol in which the goal is to gain knowledge, not necessarily to benefit the individual being treated. As the Belmont Report, the basis of all human subjects research regulations in the U.S. states:

By contrast, the term “research’ designates an activity designed to test an hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge (expressed, for example, in theories, principles, and statements of relationships). Research is usually described in a formal protocol that sets forth an objective and a set of procedures designed to reach that objective.

When a clinician departs in a significant way from standard or accepted practice, the innovation does not, in and of itself, constitute research. The fact that a procedure is “experimental,” in the sense of new, untested or different, does not automatically place it in the category of research. Radically new procedures of this description should, however, be made the object of formal research at an early stage in order to determine whether they are safe and effective. Thus, it is the responsibility of medical practice committees, for example, to insist that a major innovation be incorporated into a formal research project.

The position statement recommends:

Surgical Innovations Requiring Formal Review

If the innovation is planned, AND:
The surgeon seeks to confirm a hunch or theory about the innovation;

OR:

The innovation differs significantly from currently accepted local practice;

OR:

Outcomes of the innovation have not been previously described;

OR:

The innovation entails potential risks for complications;

OR:

Specific or additional patient consent appears appropriate,

Then:

a) The described review by a local surgical innovations committee is required, plus
b) submission to the national innovations registry is required, and
c) additional informed consent is required of the patient specific to the nature of the proposed innovation.

The recommendations also state that such innovations must comply with FDA and NIH regulations and that informed consent must be obtained, except in the case of emergency surgery, in which case the patient must be informed afterwards, in the case of “unanticipated innovation.” (Of course, one surgeon’s “unanticipated innovation” is another surgeon’s “surgical misadventure.”) It was also recommended that, if all possible, such innovations should be tried out first in an animal before being performed on humans. A further recommendation that was discussed at the SUS meeting but apparently didn’t make its way into the final draft was the creation of a “national innovations registry,” to which surgeons could report their attempted innovations and how they worked. This would be particularly important because most innovations do not work, and some even cause harm. If a surgeon is thinking of trying a new innovation, it would be useful if that surgeon could consult a database to see if someone had tried it before. After all, what’s the first thing we scientists do when considering embarking on a new research project? We hit the scientific literature, of course, to see if anyone has done anything like what we’re thinking of doing before! Scientists have PubMed; many, if not most, innovations, particularly the ones that don’t work, are never published in the peer-reviewed literature. The final recommendation was that “innovation review committtees” be set up to review attempts at surgical innovations. These would tend to be ad hoc committees based on the specific case and far more informal than an institutional review board.

Of course, the distinction between tinkering and innovation (and, for that matter, research) is artificial, and definitely somewhat arbitrary. It all really exists as a continuum. Consider the example of Dr. Schwab’s “minicholecystectomy” again. It’s really a remarkable story of how a surgical procedure, in the hands of a skilled surgeon, evolved over time. Simply by trying to decrease the size of the incision in a systematic fashion, Dr. Schwab ultimately ended up changing his practice. He started using a headlight, special instruments, and a different surgical technique to get the gallbladder out. Ultimately, his consistent tinkering led to innovation, and, I daresay, had it not been for the sudden advent of laparoscopic cholecystectomy in the late 1980’s and early 1990’s, the mini-cholecystectomy that he and others developed would likely have propagated far and wide among surgeons and become the preferred technique for removing gallbladders. In terms of the scientific method, tinkering could be looked at as the stage of hypothesis generation, while innovation could be considered preliminary testing and refining of the hypothesis. The actual research is then the stage where the refined hypothesis is subjected to rigorous testing in a highly controlled, protocolized manner.

Oddly enough, laparosocopic cholecystectomy (LC) is a great example of an innovation that rather got ahead of itself. The potential benefits of the procedure in terms of decreased hospital stay, decreased postoperative pain, and faster return to work were obvious and quickly recognized. However, this procedure, perhaps more than any other, reveals some of the pitfalls in surgical innovation. For one thing, it revealed the effects of marketing and patient demand. Surgeons who learned how to do LCs in those heady early days advertised it heavily, and patients came to see the new procedure as obviously superior to the old before there was much comparative data on complication rates. They started to demand it, and more and more surgeons felt obligated to learn it even before the data from research (formal definition) was all in, lest their patients go elsewhere and their referring physicians abandon them. Eventually, as the research was finally done, it became apparent that there was a considerably higher rate of common bile duct injuries in LC compared to the old method. Granted, it was still a very small number, but the number was nearly ten times smaller still using the boring, old-fashioned open approach to taking gallbladders out, and common bile duct injuries can be devastating, requiring large operations to repair. In the end, it was fairly clear that the benefits outweighed the larger (albeit still very small) risk of common bile duct injuries with LC, but by the time that information was known the procedure had almost entirely supplanted the older procedure. There was no chance to weigh the risk-benefit ratio of LC in anything approaching a calm, measured fashion before introducing the procedure; the analysis was all done after the “cat was out of the bag,” so to speak. Ironically, Sid’s mini-cholecystectomy produced similar good results in his hand to LC; maybe it would have been a better, albeit less sexy, alternative, although it’s always possible that there were complications that would only become apparent if thousands of patients were studied. That’s why innovation needs to be accompanied by research.

There are many problems in considering innovations and research, not the least of which are issues of liability. As one surgeon at the session three years ago asked: “When does ‘innovation’ plus bad outcome equal departure from the standard of care?” The answer was not that encouraging. Innovation by definition is departure from the standard of care, and in the case of a bad outcome it can be a big problem. Surgical innovation committees can ameliorate this problem somewhat by giving cover to the surgeon, as can rigorous informed consent, but clearly in this litigious age the threat of being sued will have a chilling effect on innovation that even these measures may not forestall. Another issue is the composition of these committees. In academic centers, finding the expertise is usually not that big of a problem, but what about in community settings, where either the expertise is lacking or the potential members of such a committee would often be riddled with conflicts of interest, given that potential members would tend to be either partners of or competitors with the surgeon involved? Finally, there is the issue of intellectual property, particularly in the case of devices, even simple ones. Surgeons will be reluctant to share their ideas in a database if they are thinking of patenting them, although it was pointed out that it’s fairly easy to protect one’s idea beforehand by filing a preliminary patent application. And, of course, we must remember that, as much as we hate to admit it, surgeons are human too. Not all of them can always be counted on to act based primarily on what they perceive to be the best interests of their patients.

The bottom line, regardless, is that academic surgeons are going to have to get used to more oversight. Vigorous self-regulation would be the best option if we can pull it off. Gone are the days of the “Wild West,” where “cowboy” surgeons could try whatever innovative idea that caught their fancy. Although many bemoan this new oversight and worry that it will quash surgical innovation, that need not be so if surgeons, rather than the government, act to codify how we distinguish between “tinkering,” innovation, and research and require the level of oversight appropriate to each: IRBs for research and something formalized, but less rigorous, for innovation. Unfortunately, since the SUS guidelines were published in 2008, I haven’t seen much evidence of their having been widely adopted.

On the other hand, what I have seen that is very encouraging is the American College of Surgeons Oncology Group (ACOSOG). Two weeks ago, I attended the Academy of Surgery of Detroit meeting at which Dr. Mitchell Posner, who ran the training program at the University of Chicago when I was a fellow there, presented data on the latest ACOSOG trials. What was most impressive was the effort to which ACOSOG goes to standardize cancer operations rigorously between surgeons. ACOSOG requires surgeons to present videotapes of their operation in order to make sure that the technique is correct and that a surgically adequate resection was performed. In essence, ACOSOG is trying to make surgical trials as close to a randomized, double-blind trial as possible and to remove as many sources of inter-surgeon variation in skill and technique as possible.

In the end, as much as we try to make it a science, surgery can never escape the fact that, by its very nature, it is also a craft. Surgeon skill matters when it comes to patient outcome, and there are often as many ways of throwing a stitch or tying a knot as there are surgeons. Unfortunately, IRBs, as currently constituted, are not sufficiently flexible to take into account tinkering versus innovation versus research. While it is probably not possible to test various new tinkerings or innovations rigorously, it is possible to be a lot more rigorous about overseeing them, preferably before the fact but at least after the fact. Such oversight is increasingly critical as “natural orifice” surgery now breathes down the neck of laparoscopic surgery as the “latest and greatest” fad in surgery. It is also possible to standardize operations as much as possible for purposes of clinical trials. All of these are important developments in the quest to make “surgical science” cease to sound like an oxymoron.

You may recall that Steve has been criticizing a certain homeopath named John Benneth for his incredible flights of–shall we say?–fancy used in defending homeopathy. As a result, Mr. Benneth (whose website is called The Science of Homeopathy) has produced a series of amazing videos that he’s posted on YouTube. Although we have a very serious mission here at SBM, we are not without a sense of humor, and that’s why we thought our readers might be interested in the sorts of commentary we have received in response to some of our efforts. The first video is called HOMEOPATHY: Jew of Nazi Medicine:

Note how Benneth likens the criticism of his pseudoscience to the persecution of Jews by the Nazis. When you see something like this, you know that Godwin’s Law has been thoroughly invoked. The second video is just as outrageous and probably NSFW given that it drops the N-word. Don’t play it if that offends you. You have been warned:

You heard it right. In this one, Mr. Benneth compares Steve’s criticism of his discussions of homeopathy to the breaking of an “uppity slave” by a slave breaker.

I have to admit that I’m a bit envious here. Steve gets all the best crank attacks directed at him for his efforts. It’s not as though a certain particularly insolent fellow hasn’t also had his fun with John Benneth’s woo-ful description of “how homeopathy works.” It’s also not as though I haven’t had some fun with certain homeopaths on this very blog.

Oh, well. I guess that, as number two, I’ll just have to try harder in the future. (I guess I’ll always have J. B. Handley.) In any case, one almost has to wonder if Benneth’s second video is a joke, given that it was posted on April Fools’ Day. What I fear is that it is not, although I do like his playing around with camera techniques and special effects in this one.

Joseph Mercola, D.O. should be well known to readers of SBM for reflexively opposing science-based medicine while providing an endless stream of misinformation on his blog, advocating detoxification, homeopathy, the tapping of meridians chiropractic and more at his clinic, and peddling a treasure trove of vitamin supplements, foods, and Mercola-endorsed devices (on sale at his site for your convenience, no conflict of interest there!).

Nothing seems to personify the evil of modern medicine to Dr Mercola more than the concept of vaccination, and Gardasil, the vaccine against human papillomavirus (HPV), has been drawing a good deal of his ire of late.  Case in point is this train-wreck of a post comparing the recent Toyota recall to Gardasil entitled “Time for the Truth About Gardasil.”  The post is ill-named.

It begins:

Cervical cancer accounts for less than 1 percent of all cancer deaths — so it was somewhat surprising when the U.S. Food and Drug Administration fast-tracked approval of Gardasil, a Merck vaccine targeting the human papilloma virus that causes the disease.

Cervical cancer tallied 11,982 new cases of cervical cancer and 3,976 deaths in 2006, not to mention the non-cervical cancers for which it is also responsible.  Worldwide it has an even greater impact as the second leading cause of cancer in women.  Unless Dr Mercola is trying to tell us that he considers the prevention of several thousand deaths per year in the US alone a waste of effort, the fact that cervical cancer isn’t one of the leading causes of cancer death in the US is irrelevant to the FDA’s approval of Gardasil.

I’m certain the actual point Dr Mercola is trying to make is that in his opinion, Gardasil was inadequately tested prior to release, and that he does not accept the data supporting its efficacy or safety.  The fact is that it was tested on over 20,000 women in stage 3 trials where both its safety and efficacy profiles were excellent while identifying a few rare but legitimate side effects, and that post-licensure studies after over 23 million doses have supported the original licensure data (I covered this topic at some length here, as has Dr David Gorski here).  If Dr Mercola insists on having such exceedingly high standards for the safety and efficacy of a vaccine, surely he holds the myriad concoctions and other products he endorses and sells on his site to the same standard.  Surely.  Right.

He then continues:

As of the end of January 2010, 49 unexplained deaths following Gardasil injections have been reported to the Centers for Disease Control and Prevention’s Vaccine Adverse Event Reporting System.

Mercola implies that the 49 “unexplained” deaths are in fact due to Gardasil (there were 48, not 49 on my check on April 2^nd, 2010).  There are two major problems with this statement.  First and foremost, an unexplained death is, by definition, unexplained.

Second, of the deaths associated with Gardasil reported to CDC’s VAERS, the majority of them are explained.  At the time of the post-licensure review published in JAMA in August of 2009, there had been 32 deaths reported following Gardasil injection occurring between 2 to 405 days after the last injection. This is the breakdown of those 32 reported deaths after investigation:

Eight of the reports were second-hand reports that could not be verified. Four were manufacturer reports with no identifying information for confirmation or medical review… Causes of death (of the remaining 20) included 4 unexplained deaths, 2 cases of diabetic ketoacidosis (1 complicated by pulmonary embolism), 1 case related to prescription drug abuse, 1 case of juvenile amyotropic lateral sclerosis, 1 case of meningoencephalitis (Neisseria meningitidis serogroup B), 1 case of influenza B viral sepsis, 3 cases of pulmonary embolism (1 associated with hyperviscosity due to diabetic ketoacidosis), 6 cardiac-related deaths (4 arrhythmias and 2 cases of myocarditis), and 2 cases due to idiopathic seizure disorder.

Keep in mind that over 23 million doses of Gardasil had been administered in the US at this point.  It would be remarkable if none of those millions of women had died within a year or so of receiving the vaccine.  A rate of death similar to that of the control population with a random smattering of causes should be expected, and is exactly what is found.  As always, correlation does not necessarily mean causation, and Dr Mercola is deprived of his greatest source of rhetoric against Gardasil.

Not that it will stop him from jumping another shark:

By contrast, 52 deaths are attributed to unintended acceleration in Toyotas, which triggered a $2 billion recall.

Holy false analogy, Batman!  He’s comparing apples to… I don’t know, mops or something.  Where to begin?  Let’s just accept the number of 52 deaths for now.  These deaths are not simply associated with unintended acceleration in Toyotas, they are attributed to them.

These are two very different things!  If Dr Mercola wants to compare 52 deaths attributed to defective Toyotas, he needs to compare it to zero deaths attributed to Gardasil, not 49.  On the other hand, if he wants his analogy to use the 49 deaths associated with Gardasil, he needs to figure out how many people have died from any cause within a year or so of riding in a Toyota.  Methinks the number will be slightly higher than 52.

Not to mention that he completely ignores the starkly different risk/benefit ratios of using Gardasil and driving a Toyota.  No one risks developing cancer or dying from not driving a Toyota.

He concludes:

There has been no recall for Gardasil, however. In fact, it is required for sixth-grade girls in D.C., Maryland, Virginia, and many other states. Merck denies any of the deaths are related to its vaccine — and of course, it is difficult for the grieving parents to prove they were.

No, Merck doesn’t deny the deaths are related to the vaccine, the data does.  There has been no recall of Gardasil because no recall is warranted, and in the meantime the vaccine is protecting millions from contracting HPV and the cancers it can cause.

My heart goes out to the grieving families to whom Dr Mercola refers; their loss is tragic regardless of its cause.  But their grief is being needlessly compounded, and the memory of those lost insulted, as Dr Mercola insists on misrepresenting the conditions of their deaths and callously exploits their loss to spread misinformation and fear of vaccination.