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Is scientific peer review a “sacred cow” ready to be slaughtered?

Peer Review

I’ve frequently noted that one of the things most detested by quacks and promoters of pseudoscience is peer review. Creationists hate peer review. HIV/AIDS denialists hate it. Anti-vaccine cranks like those at Age of Autism hate it. Indeed, as a friend of mine, Mark Hoofnagle, pointed out several years ago, pseudoscientists and cranks of all stripes hate it. There’s a reason for that, of course, namely that it’s hard to pass peer review if you’re peddling pseudoscience, although, unfortunately, with the rise of “integrative medicine,” it’s nowhere near as difficult as it once was.

Be that as it may, peer review, the process by which scientific papers are evaluated by scientific “peers” to look for problems with the science and decide if the paper is appropriate for publication in a scientific journal, is a concept that dates back hundreds of years. However, for the most part, before the middle of the 20th century, the ultimate determination of whether a paper was appropriate for scientific publication was made by editors or editorial committees. Opinions of external reviewers were sometimes sought when deemed appropriate by journal editors, but by no means was this the practice for most manuscripts. Over the last six or seven decades, external peer review by scientists chosen by the journal editor evaluating a submission has become the standard. Similarly, decisions regarding whether or not to fund grant applications are now generally made by a panel of external reviewers. In the case of the NIH, these panels are called study sections and consist of scientists with expertise in the types of applications being referred to the study section for evaluation, along with (usually) a statistician or two and officials from the NIH who take care of organizing and running the meetings of the panel. The scientific members of a study section usually include “permanent” members, who are assigned to fixed terms on the study section, and ad hoc members, called in for one or a few meetings as needed and deemed necessary by the NIH.
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Posted in: Basic Science, Clinical Trials, Science and Medicine

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Worshiping at the altar of the Cult of the Brave Maverick Doctor

Death of Cancer

One of my favorite television shows right now is The Knick, as I described before in a post about medical history. To give you an idea of how much I’m into The Knick, I’ll tell you that I signed up for Cinemax for three months just for that one show. (After its second season finale airs next Friday, I’ll drop Cinemax until next fall.) The reason why I’m bringing up The Knick (besides I love the show and need to bring it up at least once a year) is because an article by Malcolm Gladwell in The New Yorker entitled “Tough Medicine“, which is a commentary based on a new book on cancer by a veritable god of cancer research, Vincent T. DeVita, Jr., immediately resonated with a storyline in this season of The Knick. I haven’t yet read The Death of Cancer: After Fifty Years on the Front Lines of Medicine, a Pioneering Oncologist Reveals Why the War on Cancer Is Winnable–and How We Can Get There by Vincent T. DeVita and Elizabeth DeVita-Raeburn, but I want to. I can tell, though, that there will be parts of the book I find annoying just from Gladwell’s take on it, which approvingly describes DeVita as railing against the cautiousness and incremental nature of today’s cancer research. To give you an idea of where Gladwell’s coming from, I note that his article shows up in the title bar of my web browser not as “Tough Medicine” but rather “How To Cure Cancer”, even as the title on the web page itself remains “Tough Medicine”. On the other hand, the article does conclude with Gladwell demonstrating a better understanding of the disadvantages of what DeVita is proposing than it seems that he will in the beginning. In fact, it is Gladwell who is more reasonable than his subject, although he does appear share DeVita’s apparent assumption that potentially all cancer patients are savable if only we try hard enough. (more…)

Posted in: Cancer, Clinical Trials, History, Medical Ethics

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Influenza Eye Roll

Look!  A metaphor!

Look! A metaphor!

I don’t know the best metaphor. What comes around goes around. The more things change, the more they say the same. Sisyphus. Whack-A-Mole.

So what to do when the same old same old rears its head yet again? There are 2,545 posts on this blog, and I suppose I could just point to prior posts. But a blog entry that consists of links to prior posts would make the managing editor irritable. And we don’t want him irritable. Although those links are at the end of the post.

And WordPress is not a good format for reference material. I have trouble finding my own articles even when I know they exist and search for them using what I think are relevant terms.

It being the start of the flu season the same ole same ole nonsense is back about flu vaccines and influenza treatment. Influenza seasons vary, the nonsense does not. On the assumption that most of the readers of the post have no prior knowledge of what I have written on the topic, I thought I would tackle influenza yet again. (more…)

Posted in: Clinical Trials, Critical Thinking, Science and Medicine

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Misinterpreting TACT: No, Chelation Does Not Outperform Statins for Heart Disease

chelation
Chelation with intravenous EDTA (disodium ethylene diamine tetra-acetic acid) has long been used for heavy metal poisoning. It binds the metal ions and facilitates their excretion from the body. In recent years it has been used for many other indications that are not evidence-based, such as autism and coronary heart disease.

The Trial to Assess Chelation Therapy (TACT) was done to assess the effectiveness and safety of EDTA plus high-dose oral vitamins for preventing second heart attacks in patients who had already had one. An article on The People’s Pharmacy website portrays the study as strongly positive. The Graedons, authors of the website, claim that science supports the use of chelation. They report that for every 12 patients undergoing chelation, one heart attack will be prevented over a five-year period. They cite a 5-year NNT (number needed to treat) of 16 for statin therapy and they conclude that:

EDTA chelation outperformed statins because fewer people needed to receive treatment to achieve a desirable outcome.

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Posted in: Clinical Trials, Science and Medicine

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Exercise and Memory

exercise-brainThere is no escaping the evidence that regular moderate exercise is associated with a host of medical benefits. Among those benefits are perhaps improved memory and cognition, and questionably a decreased risk of developing dementia.

The latest study to show this correlation involved younger and older adults who wore a step-monitor. The number of steps they took during the study interval was then correlated with their performance on neuropsychological testing. The researchers found that for the older adults, but not younger adults, more physical activity correlated with better overall cognitive performance, but especially for face-name recognition.

This is a small study, with 60 subjects total. Also, the study is correlational only. It is possible that healthier older adults are both more physically active and cognitively nimble, because of underlying biological fitness. More cognitively active older adults may also be more physically active – the lines of cause and effect are plausible in multiple ways. (more…)

Posted in: Clinical Trials, Neuroscience/Mental Health

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Acupuncture/TCPM Crapfest

Acupuncture needling

Look Ma! No gloves!

As I get older I get more grumpy. Issues that at one time I was rather sanguine about, now irritate the hell out of me. It is not like it was when I started practice. Information was hard to come by. Going through the Index Medicus, with the world’s tiniest font, wandering the stacks looking for papers, sending off for reprints, getting a precious Xerox (or even a mimeograph) of a classic paper from an attending.

You understood the value of eminence-based medicine, as it took a career to acquire and master the literature. You relied on the wisdom of old geezers like me who had decades of experience and reading.

That was then. Now? The world’s information is available almost instantaneously. You may not be able to master a new topic spending a day on Google and Pubmed, but you can acquire a reasonable understanding, especially of you have some background.

Because of Google and Pubmed, the only reasons for ignorance of your area of expertise in medicine are time, laziness, or stupidity. As a specialist, only time is an excuse. It is my job to keep up with infectious diseases, although with over 10,000 articles a year in ID, it is impossible to read everything. But if I have a question concerning patient care, I need to look it up. I have another blog whose raison d’être is looking up answers to the daily questions that arise in practice.

On the characteristics of a useful clinical trial

So the characteristics of a useful clinical trial are not hard to determine: Randomized, double blind, placebo controlled, adequately powered. Because you want to avoid spending time and money on a study only to end up with no useful conclusions. This is especially important with acupuncture where it not does matter what kind of acupuncture is used, if needles are used, where the needles are placed or even if you mime acupuncture or perform acupuncture on a rubber hand. The key features for success in acupuncture are belief that the patient is receiving acupuncture and that the patient believes the acupuncture will be effective. And the stronger the belief, the better the subjective response. (more…)

Posted in: Acupuncture, Clinical Trials, Traditional Chinese Medicine

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The elusive “potential” of integrative medicine

The Integrative Medicine Wheel

The Integrative Medicine Wheel

 

UPDATE: Dr. Katz has responded to this post in his usual venue, The Huffington Post.

Alternative medicine was all about “potential” from the get go:

In 1991, the Senate Appropriations Committee responsible for funding the National Institutes of Health (NIH) declared itself “not satisfied that the conventional medical community as symbolized at the NIH has fully explored the potential that exists in unconventional medical practices.”

Thus, the Committee, led by chair Sen. Tom Harkin, directed the NIH to create an advisory panel that would “fully test the most promising unconventional medical practices.”

The advisory panel became the Office of Alternative Medicine, which became the National Center for Complementary and Alternative Medicine, which became the National Center for Complementary and Integrative Medicine, its current iteration.

This effort to unlock the “potential” of unconventional (renamed alternative, renamed complementary and alternative, renamed integrative) medicine forced an uncomfortable alliance between science and pseudoscience from the beginning. Advocates like Harkin, and his two quackery-promoting constituents, Berkeley Bedell (colostrum and something called “714-X,” derived from camphor) and Frank Wiewel (immuno-augmenative therapy for cancer), were all for “fully testing” until they realized what “fully testing” meant to a scientist: double-blind, placebo controlled trials. It was thus that the true believers discovered the value of special pleading: they “favored quick field studies that would validate alternative treatments.”

Taxpayer monies flowed into legitimate medical and scientific research institutions to conduct alternative medicine research: the Maryland School of Medicine, Harvard Medical School, University of California at Davis, and the Texas Health Science Center, among others, received funds for the study of antineoplastons, cartilage products, magnets, mind-body control, and even Bedell and Wiewel’s beloved “714-X” and immuno-augmentative therapy. (more…)

Posted in: Clinical Trials, Medical Academia, Public Health

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Are Placebos Getting Stronger?

placebo1A new study looked at clinical trials for neuropathic pain over the last 23 years and found that the response of subjects in the placebo group has been increasing over time, but only in the United States. The cause of this increase is unknown, and has provoked a fascinating discussion about the nature of placebos and their role in medical research.

What is the placebo effect?

We have discussed the placebo response at length here at SBM because the concept is critical to understanding clinical science, and it is largely misunderstood. Most often it is presented as a mind-over-matter response to the expectation of benefit. Proponents of worthless treatments often hype the placebo response as if it can have real healing power, when the evidence shows it does not.

In reality, there are a large number of placebo effects and the phenomenon is quite complex. In clinical trials “the placebo effect” is whatever happens in the placebo group of the study, the group receiving an inactive treatment. This is not one effect, however, but a complex combination of many effects.

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Posted in: Clinical Trials

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Choosing Wisely: Changing medical practice is hard

OK, so Choosing Wisely isn't quite like this, but it's still very important.

OK, so Choosing Wisely isn’t quite like this, but it’s still very important.

We here at Science-Based Medicine like to point out that arguably the most striking difference between science-based medicine (and the evidence-based medicine from which we distinguish it) and alternative medicine, “complementary and alternative medicine” (CAM), or (as it’s called now) “integrative medicine” is a concerted effort to change for the better. In other words, in SBM, we are continually doing studies to improve practice. These studies take on two general forms: Comparing new treatments with old to determine if the new treatments work better and, as has become an imperative over the last several years supported by more research dollars, comparing existing treatments in order to determine which ones work better. In the case of the former, we are trying to add to our knowledge and thereby add more effective treatments, while in the case of the latter we are trying to weed out treatments that are less effective and/or less safe or that cost more money to produce the same results. Indeed, the rise of an explicit framework, evidence-based medicine, is a result of the desire of medicine as a profession to improve what it is doing. (Yes, I know this blog frequently criticizes EBM, but in the case of treatments that have science behind them EBM and SBM should be—and usually are—synonymous.) This is in marked contrast to CAM, where treatments based on prescientific vitalism never, ever go away, no matter how many clinical trials show them to be no better than placebo and basic science shows them to be ludicrously disconnected from reality.

An example of this imperative to make things better is Choosing Wisely. This is an initiative launched in 2012 in which the American Board of Internal Medicine (ABIM) Foundation challenged specialty societies to produce lists of tests and interventions that doctors in their specialty routinely use but that are not supported by evidence. The explicit goal of Choosing Wisely was to identify and promote care that is (1) supported by evidence; (2) not duplicative of other tests or procedures already received; (3) free from harm; and (4) truly necessary. In response to this challenge, medical specialty societies asked their members to “choose wisely” by identifying tests or procedures commonly used in their field whose necessity should be questioned and discussed. The resulting lists of “Things Providers and Patients Should Question” was designed to spark discussion about the need—or lack thereof—for many frequently ordered tests or treatments.
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Posted in: Clinical Trials, Politics and Regulation, Quality Improvement

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The Amarin case: off-label promotion and a double standard for prescription drugs vs. dietary supplements

Screenshot 2015-10-14 23.04.19

A recent court decision enjoined the FDA from threatening prosecution against a drug manufacturer for off-label promotion of a prescription drug. Based on this and an earlier decision by an appellate court, it appears that the FDA can no longer prosecute a pharmaceutical manufacturer for a truthful and non-misleading off-label promotion to health care professionals, at least within the jurisdiction of the United States Court of Appeal for the Second Circuit, which covers Connecticut, New York and Vermont.

For this reason, the case, Amarin Pharma, Inc. v. FDA (Amarin), received a good deal of attention in the world of drug regulation. (Here is an excellent analysis by two attorneys who practice in the area of drug regulation.) First, we’ll take a look at the issue of off-label promotion. Then we’ll look at an issue that really didn’t engender much comment, but that I find fascinating: how the same substance can be subject to very different regulatory treatment, depending on whether it is sold as a dietary supplement or prescription drug.

Background: Initial approval of Vascepa and subsequent research

In 2012, the pharmaceutical manufacturer Amarin received FDA approval for a new drug, Vascepa, as an adjunct to diet to reduce triglyceride levels in adult patients with severe hypertriglyceridemia (triglycerides ≥ 500mg/dL). Approval was based on a single phase 3 clinical trial.

Following that approval, Amarin designed a second single phase 3 clinical trial to look at the effect of Vascepa on triglyceride levels among statin-treated patients with persistently high triglycerides (≥ 200 and ≤ 500 mg/dL). Pursuant to an agreement with the FDA that, if it met certain conditions, Vascepa would obtain approval for this use, Amarin proceeded with an FDA-approved protocol. As a further condition of the agreement, it also began enrolling patients in a third trial to see if Vascepa actually reduced major cardiac events. (more…)

Posted in: Clinical Trials, Herbs & Supplements, Legal, Nutrition, Pharmaceuticals, Politics and Regulation

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