Archive for Clinical Trials

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.


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.

Posted in: Clinical Trials, Politics and Regulation

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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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October is National Chiropractic Health Month!

October is National Chiropractic Health Month (NCHM) and chiropractors can’t resist the opportunity to overstate, obfuscate, and prevaricate in celebration.

They do this in the face of some unfortunate (for them) statistics revealed by a recent Gallup Poll. The Poll was paid for by Palmer College of Chiropractic as part of an effort to increase the chiropractic share of the health care pie. (There is also a secondary analysis of the poll in the Journal of Manipulative and Physiological Therapeutics.) We’ll get to those stats in a few minutes.

But first, in celebration of NCHM, the American Chiropractic Association (ACA) has produced a set of six graphics chiropractors can download and display. Four of them fudge on the facts. Let’s take a look at these graphics, compare them to the evidence cited in support of their claims, and see where the ACA went astray. (The ACA also hosted a twitter chat yesterday with the hashtag #PainFreeNation.)


The study cited as evidence for this graphic actually compared both manual thrust manipulation (MTM) and mechanical-assisted manipulation (MAM) to each other as well as manipulation versus usual medical care (UMC). Although MAM, such as the Activator Method, is the second most common manipulation technique used by American chiropractors, is increasing in popularity among them, and is touted to be a safe and effective alternative to MTM, this study found that MTM is more effective (at 4 weeks) than MAM and that MAM had no advantage over UMC. But you don’t see that in this graphic.


Posted in: Chiropractic, Clinical Trials, Critical Thinking

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The Worst Homeopathy Study. Ever

A rare double-face palm, so you can't see the tears

A rare double-face palm, so you can’t see the tears

I run across a lot of information in my feeds that I need to save for further evaluation. The study “Does additional antimicrobial treatment have a better effect on URTI cough resolution than homeopathic symptomatic therapy alone? A real-life preliminary observational study in a pediatric population“, I saved with the file name, ‘jaw droppingly stupid’.

The worst homeopathy clinical trial ever doesn’t spring full formed like Athena from the head of Zeus. No. The worst homeopathy clinical trial ever started with a seed. The seed is “Homeopathic medicine for acute cough in upper respiratory tract infections and acute bronchitis: A randomized, double-blind, placebo-controlled trial, which is a standard lousy homeopathic study. (more…)

Posted in: Clinical Trials, Ethics, Homeopathy

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Battle of the feds: FTC tells FDA to do its job regulating homeopathy

Two institutions duke it out: FTC vs FDA.

Two institutions duke it out: FTC versus FDA.

Last month, the Society for Science-Based Medicine submitted a comment to the Food and Drug Administration (FDA) in response to its request for public comments on the agency’s current regulation (actually, lack of regulation) of homeopathic drugs. As the SFSBM pointed out, the FDA has, without legal authority, exempted homeopathic drugs from the safety and efficacy requirements applicable to other drugs under the Food, Drug and Cosmetic Act (FD&C Act). Lax regulation has resulted in consumer confusion: consumers do not understand homeopathy, how the FDA regulates homeopathic drugs, and the lack of scientific evidence underlying claims made by homeopathic drug companies.

As it turns out, we were in excellent company. The Federal Trade Commission (FTC), the agency charged with preventing fraudulent and deceptive business practices, submitted its own comment to the FDA, making these same points. (The FTC is holding its own workshop on advertising homeopathic drugs later this month. We’ll get to that shortly.)

The FTC’s advertising substantiation policy requires that health-related efficacy claims be supported by competent and reliable scientific evidence. The FDA, despite federal law, does not require evidence of efficacy for homeopathic drugs prior to their being marketed. This creates a potential conflict between the two regulatory schemes, resulting in homeopathic over-the-counter (OTC) “drugs” on the market that both comply with FDA’s policy and violate FTC’s policy. This, says the FTC, can be harmful to consumers and create confusion for advertisers. The FTC “recommends that the FDA reconsider its regulatory framework for homeopathic medicines” and tells the FDA what it can do to remedy the situation. (more…)

Posted in: Clinical Trials, Health Fraud, Homeopathy, Legal, Politics and Regulation

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“Precision medicine”: Hope, hype, or both?

The cost to sequence a whole genome has been plummeting impressively since 2007.

The cost to sequence a whole genome has been plummeting impressively since 2007.

I am fortunate to have become a physician in a time of great scientific progress. Back when I was in college and medical school, the thought that we would one day be able to sequence the human genome (and now sequence hundreds of cancer genomes), to measure the expression of every gene in the genome simultaneously on a single “gene chip,” and to assess the relative abundance of every RNA transcript, coding and noncoding (such as microRNAs) simultaneously through next generation sequencing (NGS) techniques was considered, if not science fiction, so far off in the future as to be unlikely to impact medicine in my career. Yet here I am, mid-career, and all of these are a reality. The cost of rapidly sequencing a genome has plummeted. Basically, the first human genome cost nearly $3 billion to sequence, while recent developments in sequencing technology have brought that cost down to the point where the “$1,000 genome” is within sight, if not already here, as illustrated in the graph above published by the National Human Genome Research Institute. Whether the “$1,000 genome” is truly here or not, the price is down to a few thousand dollars. Compare that to the cost of, for instance, the OncoType DX 21-gene assay for estrogen receptor-positive breast cancer, which costs nearly $4,000 and is paid for by insurance because its results can spare many women from even more expensive chemotherapy.

So, ready or not, genomic medicine is here, whether we know enough or not to interpret the results in individual patients and use it to benefit them, so much so that President Obama announced a $215 million plan for research in genomic mapping and precision medicine known as the Precision Medicine Initiative. Meanwhile, the deeply flawed yet popular 21st Century Cures bill, which passed the House of Representatives, bets heavily on genomic research and precision medicine. As I mentioned when I discussed the bill, it’s not so much the genomic medicine funding that is the major flaw in the bill but rather its underlying assumption that encouraging the FDA to decrease the burden of evidence to approve new drugs and devices will magically lead to an explosion in “21st century cures,” the same old antiregulatory wine in a slightly new bottle. Be that as it may, one way or the other, the federal government is poised to spend lots of money on precision medicine.

Because I’m a cancer doctor, and, if there’s one area in medicine in which precision medicine is being hyped the hardest, it’s hard for me not to think that the sea change that is going on in medicine really hit the national consciousness four years ago. That was when Walter Isaacson’s biography of Steve Jobs revealed that after his cancer had recurred as metastatic disease in 2010. Jobs had consulted with research teams at Stanford, Johns Hopkins, and the Broad Institute to have the genome of his cancer and normal tissue sequenced, one of the first twenty people in the world to have this information. At the time (2010-2011), each genome sequence cost $100,000, which Jobs could easily afford. Scientists and oncologists looked at this information and used it to choose various targeted therapies for Jobs throughout the remainder of his life, and Jobs met with all his doctors and researchers from the three institutions working on the DNA from his cancer at the Four Seasons Hotel in Palo Alto to discuss the genetic signatures found in Jobs’ cancer and how best to target them. Jobs’ case, as we now know, was a failure. However much Jobs’ team tried to stay one step ahead of his cancer, the cancer caught up and passed whatever they could do. (more…)

Posted in: Basic Science, Cancer, Clinical Trials, Science and the Media

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