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Plausibility bias? You say that as though that were a bad thing!

On Friday, you might have noticed that Mark Crislip hinted at a foreshadowing of a blog post to come. This is that blog post. He knew it was coming because when I saw the article that inspired it, I sent an e-mail to my fellow bloggers marking out my territory like a dog peeing on every tree or protecting my newfound topic like a mother bear protecting her cubs. In other words, I was telling them all to back off. This article is mine.

Mine! Mine! Mine! I tell you!

My extreme territorial tendencies (even towards my friends and colleagues) notwithstanding on this issue aside, if you read Mark’s post (and if you didn’t go back and read it now—seriously, go now), you might also remember that he was discussing a “reality bias” in science-based medicine (SBM), a bias that we like to call prior plausibility. In brief, positive randomized clinical trials (RCTs) testing highly implausible treatments are far more likely to be false positives than RCTs testing more plausible treatments. That is the lesson that John Ioannidis has taught us and that I’ve written about multiple times before, as have other SBM bloggers, most prominently Kimball Atwood, although nearly all of us have chimed in at one time or another about this issue.

Apparently a homeopath disagrees and expressed his disagreement in an article published last week online in Medicine, Health Care, and Philosophy entitled Plausibility and evidence: the case of homeopathy. You’ll get an idea of what it is that affected us at SBM like the proverbial matador waving his cape in front of a bull by reading this brief passage from the abstract:

Prior disbelief in homeopathy is rooted in the perceived implausibility of any conceivable mechanism of action. Using the ‘crossword analogy’, we demonstrate that plausibility bias impedes assessment of the clinical evidence. Sweeping statements about the scientific impossibility of homeopathy are themselves unscientific: scientific statements must be precise and testable.

Scientific. You keep using that word. I do not think it means what you think it means. Of course, his being a homeopath is about as close to a guarantee as I can think of that a person doesn’t have the first clue what is and is not scientific. If he did, he wouldn’t be a homeopath. Still, this particular line of attack is often effective, whether yielded by a homeopath or other CAM apologist. After all, why not test these therapies in human beings and see if they work? What’s wrong with that? Isn’t it “close-minded” to claim that scientific considerations of prior plausibility consign homeopathy to the eternal dustbin of pseudoscience?

Not at all. There’s a difference between being open-minded and being so “open-minded” that your brains threaten to fall out. Guess which category homeopaths like Rutten fall into. But to hear them tell it, homeopathy is rejected because because we scientists have a “negative plausibility bias” towards it. At least, that’s what Rutten and some other homeopaths have been trying to convince us. This article seems to be an attempt to put some meat on the bones of their initial trial balloon of this argument published last summer, which Steve Novella duly deconstructed.

Before I dig in, however, I think it’s necessary for me to “confess” my bias and why I think it should be your bias too.
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Posted in: Basic Science, Clinical Trials, Homeopathy, Science and Medicine

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Supplements and cancer prevention

The bloggers here have been very critical of a law passed nearly 20 years ago, commonly referred to as the DSHEA of 1994. The abbreviation DSHEA stands for about as Orwellian a name for a law as I can imagine: the Dietary Supplement Health and Education Act. Of course, as we’ve pointed out time and time again, the DSHEA is not about health, and it’s certainly not about education. Indeed, perhaps my favorite description of this law comes from our very own Peter Lipson, who refers to it as a “travesty of a mockery of a sham.” Rather, it’s about allowing supplement manufacturers and promoters of so-called “complementary and alternative medicine” (CAM, with or without a preceding “s,” depending on your taste) who do not want pesky things like government laws and regulations to interfere with their selling of pseudoscience to market various compounds as “dietary supplements” with near-impunity. As Harriet Hall put it so accurately, the DSHEA is “a stealth weapon that allows the sale of unproven medicines just as long as you pretend they are not medicines.”

The DSHEA accomplishes this by making a seemingly reasonable distinction between food and medicine and twisting it in such a way that allows manufacturers to label all sorts of botanicals and various other compounds, many of which have substances in them with pharmacological activity, and sell them as “supplements” without prior approval by the FDA before marketing. As long as the manufacturer is careful enough not to make health claims that are too specific, namely that the supplement can diagnose or treat any specific disease, and sticks to “structure-function” statements (“it boosts the immune system!”), almost anything goes, particularly if a Quack Miranda Warning is included.

Not surprisingly, given what a big business supplements have become in this country largely due to the DSHEA, manufacturers and CAM advocates fight tooth and nail against any attempt to update the DSHEA to correct some of its more unfortunate consequences. Led by Utah Senator Orrin Hatch and Iowa Senator Tom Harkin, who together make up a bipartisan tag-team in defense of the supplement industry and do their best to block any effort to increase its regulation by the FDA. We saw that most recently when Arizona Senator John McCain, of all people, introduced a bill in 2010 to try to tighten up the DSHEA and was thoroughly slapped down by Orrin Hatch. More recently, not satisfied with how good things are for the supplement industry, another Utah Representative Jason Chaffetz reached across the aisle to Jared Polis, teaming up to introduce the Free Speech About Science Act, which basically seeks to allow the supplement industry to make more liberal claims about its products. All it will need is a “peer-reviewed” paper to support it (Mark and David Geier would do!), and you can claim almost anything. Anything to grow the supplement industry, which is currently around $30 billion a year.

That’s why it’s critical, from time to time, to look at actual evidence, and just last week Maria Elena Martinez, PhD, of the University of California San Diego, and co-authors did in a commentary published online in the Journal of the National Cancer Institute entitled Dietary Supplements and Cancer Prevention: Balancing Potential Benefits Against Proven Harms.
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Posted in: Cancer, Herbs & Supplements, Politics and Regulation

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The problem with preclinical research? Or: A former pharma exec discovers the nature of science

If there’s one thing about quacks, it’s that they are profoundly hostile to science. Actually, they have a seriously mixed up view of science in that they hate it because it doesn’t support what they believe. Yet at the same time they very much crave the imprimatur that science provides. When science tells them they are wrong, they therefore often try to attack the scientific method itself or claim that they are the true scientists. We see this behavior not just in quackery but any time scientific findings collide with entrenched belief systems, for example, medicine, evolution, anthropogenic global warming, and many others. So it was not surprising that a rant I saw a few weeks ago by a well-known supporter of pseudoscience who blogs under the pseudonym of Vox Day caught my interest. Basically, he saw a news report about an article in Nature condemning the quality of current preclinical research. From it, he draws exactly the wrong conclusions about what this article means for medical science:

Fascinating. That’s an 88.6 percent unreliability rate for landmark, gold-standard science. Imagine how bad it is in the stuff that is only peer-reviewed and isn’t even theoretically replicable, like evolutionary biology. Keep that figure in mind the next time some secularist is claiming that we should structure society around scientific technocracy; they are arguing for the foundation of society upon something that has a reliability rate of 11 percent.

Now, I’ve noted previously that atheists often attempt to compare ideal science with real theology and noted that in a fair comparison, ideal theology trumps ideal science. But as we gather more evidence about the true reliability of science, it is becoming increasingly obvious that real theology also trumps real science. The selling point of science is supposed to be its replicability… so what is the value of science that cannot be repeated?

No, a problem with science as it is carried out by scientists in the real world doesn’t mean that religion is true or that a crank like Vox is somehow the “real” intellectual defender of science. Later, Vox doubles down on his misunderstanding by trying to argue that the problem in this article means that science is not, in fact, “self-correcting.” This is, of course, nonsense in that the very article Vox is touting is an example of science trying to correct itself. Be that at it may, none of this is surprising, given that Vox has demonstrated considerable crank magnetism, being antivaccine, anti-evolution, an anthropogenic global warming denialist, and just in general anti-science, but he’s not alone. Quackery supporters of all stripes are jumping on the bandwagon to imply that this study somehow “proves” that the scientific basis of medicine is invalid. A writer at Mike Adams’ wretched hive of scum and quackery, NaturalNews.com, crows:

Begley says he cannot publish the names of the studies whose findings are false. But since it is now apparent that the vast majority of them are invalid, it only follows that the vast majority of modern approaches to cancer treatment are also invalid.

But does this study show this? I must admit that it was a topic of conversation at the recent AACR meeting, given that the article was published shortly before the meeting. It’s also been a topic of e-mail conversations and debates at my very own institution. But do the findings reported in this article mean that the scientific basis of cancer treatment is so off-base that quackery of the sort championed by Mike Adams is a viable alternative or that science-based medicine is irrevocably broken?

Not so fast there, pardner…
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Posted in: Basic Science, Cancer, Clinical Trials

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Cancer care in the U.S. versus Europe: Is more necessarily better?

The U.S. is widely known to have the highest health care expenditures per capita in the world, and not just by a little, but by a lot. I’m not going to go into the reasons for this so much, other than to point out that how to rein in these costs has long been a flashpoint for debate. Indeed, most of the resistance to the Patient Protection and Affordable Care Act (PPACA), otherwise known in popular parlance as “Obamacare,” has been fueled by two things: (1) resistance to the mandate that everyone has to buy health insurance, and (2) the parts of the law designed to control the rise in health care costs. This later aspect of the PPACA has inspired cries of “Rationing!” and “Death panels!” Whenever science-based recommendations are made that suggest ways to decrease costs by reevaluating screening tests or decreasing various tests and interventions in situations where their use is not supported by scientific and clinical evidence, whether by the government or professional societies, you can count on it not being long before these cries go up, often from doctors themselves.

My perspective on this issue is that we already “ration” care. It’s just that government-controlled single payer plans and hybrid private-public universal health care plans use different criteria to ration care than our current system does. In the case of government-run health care systems, what will and will not be reimbursed is generally chosen based on evidence, politics, and cost, while in a system like the U.S. system what will and will not be reimbursed tends to be decided by insurance companies based on evidence leavened heavily with business considerations that involve appealing to the largest number of employers (who, let’s face it, are the primary customers of health insurance companies, not individuals insured by their health insurance plans). So what the debate is really about is, when boiled down to its essence, how to ration care and by how much, not whether care will be rationed. Ideally, how funding allocations are decided would be based on the best scientific evidence in a transparent fashion.

The study I’m about to discuss is anything but the best scientific evidence.
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Posted in: Cancer, Diagnostic tests & procedures, Politics and Regulation, Science and the Media

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Why haven’t we cured cancer yet? (Revisited): Personalized medicine versus evolution

About a year ago, I addressed what might seem to the average reader to be a very simple question: Why haven’t we cured cancer yet? As I pointed out at the time, it’s a question that I sometimes even ask myself, particularly given that cancer has touched my life. Three years ago, my mother-in-law died of a particularly nasty form of breast cancer. Even though I am a breast cancer surgeon, I still wonder why there was nothing that could save her (and there still is nothing that could have saved her, if it existed then) from a decline over several months followed by an unpleasant death. Yet, as a cancer researcher, I do understand somewhat. A couple of years ago, I wrote in depth about the complexity of cancer from a science-based viewpoint, as compared, of course, to the incredibly simplistic view that many purveyors of alternative medicine quackery promote as being The One True Cause of Cancer. As I put it at the time, shamelessly stealing from Douglas Adams: Cancer is complicated. You just won’t believe how vastly, hugely, mind-bogglingly complicated it is. I mean, you may think algebra is complicated, but that’s just peanuts to cancer.

I saw more evidence of that at the American Association for Cancer Research meeting last week. In fact, if there’s anything I’ve learned, it’s that developing personalized therapy for cancer is going to be a hell of a lot more difficult than we had ever suspected. Actually, it wasn’t just the AACR meeting that taught me this, but it’s as good a pretext as any to discuss some cool new science. I only wish it was science that pointed an obvious path forward to the development of personalized therapy. On the other hand, if it were easy then anyone could do the “personalized therapy for dummies” approach that, for example, Stanislaw Burzynski takes. Then there’s the even more ridiculously simplistic approach that certain practitioners of “complementary and alternative medicine” (CAM) take.

So why haven’t we cured cancer yet? Again? One reason that I discussed last time I covered this topic concerns a study that used the latest next generation sequencing (NGS) techniques to sequence seven aggressive and advanced prostate cancers. I described the results as these genomes looking like someone threw a miniature grenade into the nucleus of a prostate epithelial cell. In other words, these are some really messed up genomes. (I wanted to use another word to describe it, but this is a family blog—sort of, anyway.) I used this example to explain once again that cancer is not a single disease. It’s hundreds of diseases. Although there are common themes in how cells become cancerous, such as loss of responsiveness to growth signals with a resultant ability to grow unchecked, evasion of programmed cell death (apoptosis), inducing the surrounding tissue to provide a blood supply (angiogenesis), evading the immune system, and invading the blood or lymphatic systems to travel elsewhere in the body and take up shop in other organs, such as liver, lung, or bone, individual cancers acquire these necessary (to the cancer) abilities through many different mechanisms. For this reason, it’s completely ridiculous to speak of a “cure for cancer.”

It’s also the reason I expressed skepticism when Steve Novella discussed a potential universal anti-cancer drug. Ditto when the press breathlessly reports studies suggesting a “universal cancer vaccine.” While these sorts of research findings are promising, they need to be put into perspective. We’ve seen their like many times before, and various cancers are still deadly diseases. In fact, my career intersected with this sort of hype back in the 1990s, when I studied combining angiogenesis inhibitors with radiation therapy in experimental models of cancer in mice. For a period of time in the late 1990s, I lived the hype. Then reality, as it always does, brought us all down to earth. Now, 15 years later, we know that angiogenesis inhibitors, although useful, are not any sort of “magic bullet” cure for all solid tumors. Like many advances before, they have now taken their place in the armamentarium of anticancer drugs, more important than some but not as important as others.

It’s even more complicated than that.

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Posted in: Basic Science, Cancer, Evolution

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Autism prevalence: Now estimated to be one in 88, and the antivaccine movement goes wild

Editor’s Note: Some of you might have seen this before, but it’s an important (and timely) enough topic that I figure it’s worth exposing to a different audience. It’s been updated and edited to style for SBM. Enjoy.

If there’s one thing that I’ve learned that I can always—and I do mean always—rely on from the antivaccine movement, it’s that its members will always be all over any new study regarding vaccines and/or autism in an effort to preemptively put their pseudoscientific spin on the results. It’s much the same way that they frequently storm into discussion threads after stories and posts about vaccines and autism like the proverbial flying monkeys, dropping their antivaccine poo hither and yon all over science-based discussions.

In any case, antivaxers are also known for not respecting embargoes. They infiltrate their way into mailing lists for journalists in which newsworthy new studies are released to the press before they actually see print and then flood their propaganda websites with their spin on the studies, either attacking the ones they don’t like or trying to imprint their interpretation on ones on which they can, all before the skeptical blogosophere—or even the mainstream press—has a chance to report. So it was late last week, when vaccine-autism cranks jumped the embargo on a CDC study that announced new autism prevalence numbers. This is nothing new; it’s the antivaccine movement’s modus operandi, which makes me wonder why the various journals don’t shut off the flow. The study, of course, was announced in press conferences and a number of news stories. No doubt by now many of you have seen them. The stories I’ve seen thus far have focused on the key finding of the CDC study, which is that the prevalence of autism in the U.S. has risen to approximately 1 in 88, a finding reported in the CDC’s Morbidity and Mortality Weekly Report.

This is how the CDC came up with the new prevalence:
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Posted in: Neuroscience/Mental Health, Public Health, Science and the Media, Vaccines

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California Bill AB 2109: The Antivaccine Movement Attacks School Vaccine Mandates Again

Of all the preventative treatments ever developed through science- and evidence-based medicine, vaccines have arguably saved more lives, prevented more illness and disability, and in general alleviated more suffering than any single class of treatments or preventative measures throughout history. Given the obvious and incredible success of vaccines at decreasing the incidence of infectious diseases that used to ravage populations, it seems incredible that there would be such a thing as an antivaccine movement, but there is. Indeed, when I first encountered antivaccine zealots on the Usenet newsgroup misc.health.alternative about ten or twelve years ago, as a physician I really had a hard time wrapping my head around the fact that such people existed. No doubt the same is true of many physicians, who take the scientific evidence for the safety and efficacy for vaccines for granted. However, I am a cancer surgeon, and I do not treat children; so until I discovered antivaccine rhetoric on the Internet I was blissfully ignorant that such views even existed. Other health care professionals knew better. Pediatricians, nurses, and any health care professionals who deal with children and the issue of vaccinations know better, because they face antivaccine views on a daily basis. It is because of the incredible importance of vaccination and the danger to public health the antivaccine movement represents that we at Science-Based Medicine write so frequently about vaccines and the antiscientific, pseudoscientific, and misinformation-packed fear mongering about vaccines that is so prevalent today.

The success of vaccination campaigns has recently been endangered by a number of factors, in particular the antivaccine movement. Because of various groups opposed to vaccination, either for philosophical reasons or because they incorrectly believe that vaccines cause autism, neurodevelopmental disorders, sudden infant death syndrome, and autoimmune diseases, among others, one of the most potent tools for encouraging high rates of vaccine uptake, school vaccine mandates, have come under attack. Alternatively, increasing numbers of parents have taken advantage of religious or philosophical exemptions in order to avoid the requirement to have their children vaccinated prior to entry to school. As a result, of late some states with lax vaccination requirements have begun to try to tighten up requirement for non-medical vaccine exemptions. The arguments used by the antivaccine movement against such legislation are highly revealing about their mindset, in particular their attitude towards issues of informed consent, which I will discuss a bit. But first, here’s a little background.
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Posted in: Politics and Regulation, Public Health, Science and the Media, Vaccines

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Keeping the customer satisfied

One thing about blogging once a week or so compared to my other blogging gig, which is usually close to every day, occasionally more often, is that I really can’t cover everything I want to cover for this blog. Even more so than at my not-so-super-secret other blogging gig, I have to pass on topics that could be fodder for what could be excellent to even awesome posts—or, self-congratulating hyperbole aside, at least reasonably interesting to the readers of this blog. When that happens, I can only hope that one of my co-bloggers picks up on it and gives the subject matter the treatment it cries out for. Or, sometimes, such subject matter just has to be dealth with elsewhere by me—or not at all. Even a hypercaffeinated blogger like myself has limits.

Sometimes, however, I actually get a second chance. In other words, I get a chance to revisit a topic that I passed by. Usually, this happens when something new happens that gives me an excuse to revisit the topic. So it was last of week, when I was perusing the New York Times by an oncology nurse named Theresa Brown. Her article was titled, appropriately enough, Hospitals Aren’t Hotels. It will become very apparent very quickly why in a moment. But first, let’s sample Brown’s article a bit, because it brings up an issue that is very pertinent to science-based medicine:
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Posted in: Clinical Trials, Diagnostic tests & procedures, Epidemiology

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An antivaccine tale of two legal actions

I don’t know what it is about the beginning of a year. I don’t know if it’s confirmation bias or real, but it sure seems that something big happens early every year in the antivaccine world. Consider. As I pointed out back in February 2009, in rapid succession Brian Deer reported that Andrew Wakefield had not only had undisclosed conflicts of interest regarding the research that he did for his now infamous 1998 Lancet paper but that he had falsified data. Then, a couple of weeks later the Special Masters weighed in, rejecting the claims of autism causation by vaccines made in three test cases about as resoundingly as is imaginable. Then, in February 2010, in rapid succession Andrew Wakefield, the hero of the antivaccine movement, was struck off the British medical register, saw his 1998 Lancet paper retracted by the editors, and was unceremoniously booted from his medical directorship of Thoughtful House, the autism quack clinic he helped to found after he fled the U.K. for the more friendly confines of Texas. Soon after that, the Special Masters weighed in again, rejecting the claims of autism causation by vaccines in the remaining test cases. Then, in January 2011, Brian Deer struck again, publishing more damaging revelations about Wakefield, referring to his work as Piltdown medicine in the British journal BMJ.

This year, things were different.
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Posted in: Politics and Regulation, Science and the Media, Vaccines

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Help a reader out: Abstracts that misrepresent the content of the paper

Earlier this week, a reader of ours wrote to Steve and me with a request:

First off, I just want to say thank you for everything you gentlemen do. I find that your sites are extremely helpful when trying to figure out what level of information is BS, and what is real.

In short, I was wondering if either of you two would be able to refer me to a scientific or psuedo-scientific article where the abstract completely misrepresents the article or the conclusion doesn’t fit the analysis/data. The reason is that I’m writing is that I’m currently in my third year at [REDACTED], and currently I’m working on my seminar paper so I can graduate. I decided to look at whether there is a reasonable fair use argument in the reproduction of an entire scientific article and at what instances prior precedent would allow it. Inherent in the argument is that a scientific paper can’t be properly excerpted without losing vital information (or that an abstract does not adequately describe the entire paper), so complete reproduction of the article is necessary to properly convey the point.

Sincerely,

A Reader

So…at the risk of being too blatant, I’ll just say that our readers are very informed and scientifically knowledgeable (excepting the odd troll, of course). Can you help another reader out and provide references that fit this reader’s request? I can think of one, but I don’t think it’s as blatant as what he has in mind. Please list your references below. Heck, we might even be able to get a post for SBM out of this if there are some interesting papers that fit the description above.

Posted in: Basic Science, Medical Academia

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