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As in 2014, “right-to-try” laws continue to metastasize in 2015, part 2

As in 2014, “right-to-try” laws continue to metastasize in 2015, part 2

When I wrote a week ago about the sham that is “right-to-try”, one criticism (among many) that I made of these misguided, profoundly patient-unfriendly laws was that I have as yet been unable to find a single example of a patient who has managed to obtain access to an experimental therapeutic through such a law, much less been helped by it. So-called “right-to-try” laws, of course, claim to provide a mechanism by which patients with terminal illnesses can obtain access to experimental therapeutics not yet approved by the FDA but still in clinical trials. They are, as I’ve pointed out, a cruel sham, placebo legislation that makes lawmakers feel as though they’ve done something good but do nothing of substance for patients while providing them with false hope. The federal government through the FDA controls drug approval, which means that states can’t compel a drug company to provide a drug to a patient, and most drug companies would not want to risk jeopardizing approval of their drug, which is what could happen if they grant access to an investigational drug under right-to-try and the patient suffers an adverse event. After all, the success rate for drugs that have passed phase 1 (which is all that right-to-try requires) in phase 3 trials is only on the order of 9-12%, meaning that that’s the most optimistic probability that such drugs would benefit a patient. In reality, it’s almost certainly much, much lower.
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Posted in: Clinical Trials, Politics and Regulation

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Should placebos be used in randomized controlled trials of surgical interventions?

Randomized controlled trial

Alone of all the regular contributors to this blog, I am a surgeon. Specifically, I’m a surgical oncologist specializing in breast cancer surgery, which makes me one of those hyper-specialized docs that are sometimes mocked as not being “real” doctors. Of course, the road to my current practice and research focus was long and involved quite a few years doing general surgery, so it is not as though I am unfamiliar with a wide variety of surgical procedures. Heck, I’m sure I could do an old-fashioned appendectomy, bowel resection, or cholecystectomy if I had to. Just don’t ask me to use the da Vinci robot or, with the exception of the case of a cholecystectomy, a laparoscope, although, given the popularity of robotic surgery, I sometimes joke that I really, really need to figure out how to do breast surgery with the robot. After all, if plastic surgeons are using it for breast reconstruction, surely the cancer surgeon should get in on the action.

I keed. I keed.

Clinical trials of surgical procedures and placebo controls

I have, however, from time to time addressed the issue of science-based surgery, and this weekend seems like as good a time to do so again, given that I just came across an article in the BMJ reporting a systematic review of the use of placebos in surgical trials. It’s a year old, but worth discussing. Before I get to discussing the nitty-gritty of this particular trial, let me just note that the evaluation of surgical procedures for efficacy and safety tends to be more difficult to accomplish than it is for medications, mainly because it’s much harder to do the gold standard clinical trial for surgical procedures, the double-blind, placebo-controlled randomized clinical trial. The two most problematic aspects of designing such an RCT in surgery, as you might imagine, are the blinding, particularly if it’s a trial of a surgical procedure versus no surgical procedure, and persuading patients to agree. I’ll deal with the latter first, because I have direct personal experience with it. (more…)

Posted in: Clinical Trials, Surgical Procedures

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As in 2014, “right-to-try” laws continue to metastasize in 2015

As in 2014, “right-to-try” laws continue to metastasize in 2015

Last year, I did several posts on what I consider to be a profoundly misguided and potentially harmful type of law known as “right-to-try.” Beginning about a year and a half ago, promoted by the libertarian think tank known as the Goldwater Institute, right-to-try laws began popping up in state legislatures, which I likened to Dallas Buyers Club laws. Both Jann Bellamy and I wrote about how these laws are far more likely to do harm than good, and that is a position that I maintain today. The idea behind these laws is to give terminally ill patients access to experimental drugs—in some cases drugs that have only passed phase I testing—that might help them. It’s an understandable, albeit flawed argument. After all, it’s perfectly understandable why terminally ill patients would fight for drugs that give them hope, and it’s just as understandable why politicians and the public would see such a goal as a good thing. In practice, as I will explain again in the context of this update, such laws are far more likely to harm patients than help them. Indeed, as you will see, in the year since the first wave of right-to-try laws have passed, not a single patient that I can find has obtained access to experimental drugs under a right-to-try law, much less been helped by them.

Unfortunately, given how effectively “right to try” has been sold on grounds of providing terminally ill patients hope and as a matter of personal freedom, it’s clear that this wave is not going to abate. Since Colorado passed the very first right-to-try law almost exactly a year ago today, a total of 17 more states now have passed passed similar legislation, the most recent being Tennessee, and 22 others have introduced legislation. It’s a good bet that right-to-try will pass in all of those states, because, as I’ve explained many times before and in many interviews, if you don’t understand clinical trial ethics and science, opposing the concept of right-to-try comes across like opposing Mom, apple pie, and the American flag, and leaves opponents open to false—but seemingly convincing—charges of callousness towards the terminally ill on the order of enjoying drop kicking puppies through flaming goalposts.
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Posted in: Clinical Trials, Pharmaceuticals, Politics and Regulation

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Stem cells versus Gordie Howe’s stroke, part 3

Gordie Howe in his Red Wings days.

Gordie Howe in his Red Wings days.

Here I am in Philadelphia attending the 2015 American Association for Cancer Research (AACR) meeting to imbibe the latest basic and translational science about oncology. So what am I doing in my non-conference time? I’m holed up in my hotel room near Rittenhouse Square writing a DoD Grant and this post. Fortunately, I am nearly done with the grant, with nothing I can do until I receive one last letter of support from a person who, as much as he’s my bud, is incredibly annoying and always makes me sit on pins and needles waiting for his letter of support. (Those of you who’ve applied for a lot of grants know what I mean.) Then tomorrow I will have to assemble the PDF package to get to my grants office two days before the deadline, which is pushing it to make sure they get it uploaded to Grants.gov in time. Fun times.

With the Stanley Cup playoffs just getting underway (complete with the ugly faux “Stanley Cup” made out of garbage cans our next door neighbor’s son puts on his lawn every year, bathed in red light for the Red Wings), it’s also the perfect time to revisit a story I’ve written about a couple of times before right here on this very blog. I’m referring (this time) to the story of hockey legend Gordie Howe and news stories of his “miraculous” recovery from a serious stroke suffered back in October due to treatment at a stem cell clinic in Tijuana back in December. Of course, when I looked into it, there were a lot of holes in the story and clearly a lot of hype on the part of several parties: Howe’s son Murray Howe, whose love for his father apparently blinded him to some rather obvious issues with the care that his father was receiving and whether it was responsible for his recovery; Stemedica, the American stem cell company based in San Diego that sells its stem cells to a dubious Mexican stem cell company, Novastem, for use outside its U.S. clinical trials; and, of course, the credulous sports media, led by that most credulous of the credulous (with respect to Gordie Howe), Keith Olbermann, who was none too pleased with a certain not-so-pseudonymous “friend” of SBM and completely embarrassed himself in the process of attacking anyone who questioned whether stem cells caused Howe’s recovery. The whole story did have one salutary effect, though. It introduced me to a real stem cell scientist, Paul Knoepfler, who did a guest post for us.

It’s been a couple of months since I last paid attention to what was going on with Gordie Howe’s recovery. Fortunately, our very own Scott Gavura tweaked me by sending me a story by Avis Favaro and Elizabeth St. Philip that appeared over the weekend in the Toronto Star, entitled “A closer look at the startling recovery of Gordie Howe.” Accompanying the story is a broadcast on CTV’s W5 entitled “Gordie’s Comeback”. (See part 1, part 2, part 3.) Also accompanying all of this is a press release discussing how a Canadian stem cell researcher visited Novastem and left unimpressed.
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Posted in: Clinical Trials, Neuroscience/Mental Health, Science and the Media

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Anesthesia-Assisted Rapid Opioid Detox

Legitimately prescribed drugs can be stolen from a medicine cabinet a few at a time, usually without notice. From the Iowa Governor's Office of Drug Control Policy.

Legitimately prescribed drugs can be stolen from a medicine cabinet a few at a time, usually without notice. From the Iowa Governor’s Office of Drug Control Policy.

Opioids are widely available as prescription drugs for pain: hydrocodone (e.g., Vicodin), oxycodone (e.g., OxyContin, Percocet), morphine (e.g., Kadian, Avinza), and codeine. Heroin, which has no medically approved use, is also an opioid. Unfortunately, opioids are also widely abused.

How enticing it is to imagine a magic bullet for opioid drug addiction. Addiction causes huge social problems. Yet it is hard to treat and suffers from a stigma that does not attach to other chronic diseases, like diabetes. Drugs like naltrexone, methadone and buprenorphine, as well as behavioral therapies, are common opioid addiction treatments, although the relapse rate for addiction treatment is high.

One of the barriers to treatment is the addict’s fear of the side effects of withdrawal, which can be extremely uncomfortable, including nausea, cramping and vomiting. It is no wonder, then, that the opioid addict and his family would be drawn to a detoxification procedure advertised as both rapid, to speed up the initiation of relapse-prevention therapy, and relatively painless: anesthesia-assisted rapid opioid detox (AAROD), sometimes called ultra-rapid detox, or even just plain rapid detox, although the latter also refers to detox under lighter sedation.

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Posted in: Clinical Trials, Legal, Pharmaceuticals, Politics and Regulation

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Integrative medicine, naturopathy, and David Katz’s “more fluid concept of evidence”

The Integrative Medicine Wheel

The Integrative Medicine Wheel

Dr. David Katz is undoubtedly a heavy hitter in the brave new world of “integrative medicine,” a specialty that seeks to “integrate” pseudoscience with science, nonsense, with sense, and quackery with real medicine. In fairness, that’s not the way physicians like Dr. Katz see it. Rather, they see it as “integrating” the “best of both worlds” to the benefit of patients. However, as we’ve documented extensively here, on our personal blogs, and even in the biomedical literature (plug, plug), what “integrative” medicine means in practice is indeed what I characterized, the infiltration of woo into medicine. This infiltration seems to have started mainly in academia—hence the term “quackademic medicine” and “quackademia”—with the steady infiltration of nonsense into medical schools and academic medical centers, but has since metastasized to the world of community hospitals. This “integration” (or, as I like to refer to it, “infiltration”) has become so pronounced that a few years ago The Atlantic published an article entitled “The Triumph of New Age Medicine“, and just last December the Journal of the National Cancer Institute (JNCI) published a monograph full of articles touting “integrative oncology,” including guidelines recommended by the Society of Integrative Oncology (SIO) for the “integrative” treatment of breast cancer symptoms.

I mention Dr. Katz for two reasons. First, he’s taken another broadside at us at Science-Based Medicine in blog entry at The Huffington Postwhere else?—entitled “Holism, Holes and Poles” that I’ve been meaning to address for a while. But before I address Dr. Katz’s most recent complaint against science-based medicine (SBM), it’s necessary to step back and look at some history.
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Posted in: Clinical Trials, Homeopathy, Medical Academia, Naturopathy

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How should the FDA regulate homeopathic remedies?

Hyland's "4 Kids Complete Allergy" homeopathic preparation (not for use with food allergies)

Hyland’s “4 Kids Complete Allergy” homeopathic preparation (not for use with food allergies), one of many unregulated, unproven over-the-counter preparations sold in the United States

The FDA announced recently that it is holding a public hearing on April 21 and 22,

to obtain information and comments from stakeholders about the current use of human drug and biological products labeled as homeopathic, as well as the Agency’s regulatory framework for such products. These products include prescription drugs and biological products labeled as homeopathic and over-the-counter (OTC) drugs labeled as homeopathic. FDA is seeking participants for the public hearing and written comments from all interested parties, including, but not limited to, consumers, patients, caregivers, health care professionals, patient groups, and industry.

It’s about time. We know that homeopathic remedies are not, and cannot be, effective. I will not plough that ground again here. Unfortunately, the FDA does not have any authority to bar these fraudulent products from sale altogether. Only Congress can do that.

In this post, I review the current regulatory framework for homeopathic products. I then explore the possibilities, given the opportunities for regulatory change presented by the FDA at this time. In doing so, I answer some of the questions posed by the FDA in its formal notice of the hearing, printed in the Federal Register.

I argue that the FDA has no statutory authority for the manner in which it currently regulates (or, actually, doesn’t regulate) homeopathic drugs. I further argue this system, largely controlled by the homeopathic industry, must be abandoned, and that there is no reason why homeopathic drugs should not be regulated just like any other OTC or prescription drug.

(Note to those wanting to submit written comments or attend the hearing: there are deadlines and other requirements for participation. You can read those in the Federal Register.)
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Posted in: Clinical Trials, Homeopathy, Legal, Politics and Regulation

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Clinical trials of homeopathy versus “respect for science”

Trojan Rabbit

A few months ago, Steve Novella and I published an article in Trends in Molecular Medicine entitled “Clinical trials of integrative medicine: testing whether magic works?” It was our first foray together into publishing commentary about science-based medicine versus evidence-based medicine, using a topic that we’ve both written extensively about over the years on this blog and our respective personal blogs. Specifically, we discussed whether it is worthwhile to do randomized clinical trials (RCTs) testing highly improbable treatments, such as reiki and homeopathy, both of which have no physical basis to believe that they do anything whatsoever. As I’ve said many times before, reiki is simply faith healing in which Eastern mysticism is substituted for Christian beliefs, and homeopathy, as we’ve discussed many times here on SBM, is vitalistic sympathetic magic with no evidence to support its two laws.

To our surprise, that article generated a fair amount of press (for example this), with accounts of it showing up in the media in various places and Steven and I being asked to do a fair number of interviews. Part of the reason, I suspect, is that the editor made the article available for free for a month after its initial publication. (Unfortunately it’s back behind the pay wall again.) Part of the reason is that, intuitively, it makes sense to people not to waste money testing what is, at its core, magic. When I followed up that publication with an article criticizing “integrative oncology” in Nature Reviews Cancer entitled “Integrative oncology: Really the best of both worlds?“, the target was well and truly on my back. Indeed, let’s just say that the Society for Integrative Oncology and the Consortium of Academic Health Centers for Integrative Medicine (CAHCIM) are quite unhappy with me. When both their letters to the editor are published (right now, only one is), I might even blog about them.

In the meantime, I want to deal with criticism published in an unexpected place, albeit not by unexpected critics. The reason is that this criticism relies on a common straw man caricature of what we are saying when we advocate science-based medicine (SBM) that considers prior plausibility in determining what modalities to test in clinical trials and understands Bayesian thinking in which prior plausibility affects posterior plausibility that a “significant” result is not a false positive in contrast to the current evidence-based medicine (EBM) paradigm, which relegates basic science knowledge, even well-established principles of science that show that something like, say, homeopathy or reiki is impossible under the current understanding of physics, chemistry and biology, to the lowest rung on the EBM pyramid. It’s also a criticism that comes up frequently enough that, even though it’s been addressed before in various ways by various SBM bloggers, it’s worth revisiting from time to time. In this case, that’s particularly so because one of the two critics taking Steve and me to task is currently embroiled in a controversy about testing homeopathy for attention deficit hyperactivity disorder (ADHD) at the University of Toronto (more details on that later). Let’s just say, the criticism of Steve and me gives me an “in” to address a story that I thought had passed me by, and I intend to take it.
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Posted in: Clinical Trials, Energy Medicine, Homeopathy

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Psychology Journal Bans Significance Testing

p-valuesThis is perhaps the first real crack in the wall for the almost-universal use of the null hypothesis significance testing procedure (NHSTP). The journal, Basic and Applied Social Psychology (BASP), has banned the use of NHSTP and related statistical procedures from their journal. They previously had stated that use of these statistical methods was no longer required but can be optional included. Now they have proceeded to a full ban.

The type of analysis being banned is often called a frequentist analysis, and we have been highly critical in the pages of SBM of overreliance on such methods. This is the iconic p-value where <0.05 is generally considered to be statistically significant.

The process of hypothesis testing and rigorous statistical methods for doing so were worked out in the 1920s. Ronald Fisher developed the statistical methods, while Jerzy Neyman and Egon Pearson developed the process of hypothesis testing. They certainly deserve a great deal of credit for their role in crafting modern scientific procedures and making them far more quantitative and rigorous.

However, the p-value was never meant to be the sole measure of whether or not a particular hypothesis is true. Rather it was meant only as a measure of whether or not the data should be taken seriously. Further, the p-value is widely misunderstood. The precise definition is:

The p value is the probability to obtain an effect equal to or more extreme than the one observed presuming the null hypothesis of no effect is true.

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Posted in: Basic Science, Clinical Trials, Science and Medicine

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Placebo, Are You There?

By Jean Brissonnet, translation by Harriet Hall

Note: This was originally published as “Placebo, es-tu là?” in Science et pseudo-sciences 294, p. 38-48. January 2011. It came to my attention in the course of an e-mail correspondence with the editors of that magazine, where one of my own articles was published in French translation in January 2015. I thought this was the best explanation of placebo that I had ever read. It covers the same points my colleagues and I have addressed and more. It describes the pertinent research and uses particularly effective graphs to illustrate the principles (a picture is worth a thousand words). The author, Jean Brissonnet, kindly gave his permission for me to translate it and share it with our readers.


In fact, you don’t need to give a placebo to get a placebo effect and therefore we can now think about how we can maximize the placebo component of routine care.

~ Damien Finniss, 2010

The scene takes place in a surgical suite where they are preparing to do a cataract operation. The patient is lying on the operating table. A few minutes earlier the anesthetic gel was applied to the cornea to permit an operation under simple local anesthesia. The surgeon arrives in the company of the anesthetist. They are engaged in a spirited discussion and don’t seem to be agreeing.

“It has been proven,” says the surgeon, “that 30% of the action of a medical treatment is due to the placebo effect.”

“I doubt that,” retorts his interlocutor, “I think that placebo story is one of those medical myths on a par with the idea that we only use 10% of our brain, that nails and hair grow after death, or that cellphones create interference in hospitals.”[1]

“No,” insists the surgeon with a superior tone, “the fact is established and has been proven by numerous studies.”

The anesthetist shakes his head with a slight smile, but he doesn’t reply. As for the patient, who might have much to say on the subject, he keeps quiet, because it would not be prudent to argue with someone who is about to suck the lens out of your eye.

This true anecdote would not be of interest if it didn’t concern two members of the medical profession. Why such uncertainty? Why such lack of knowledge about such a fundamental subject? This faith in an all-powerful, magical, and mysterious placebo is common among the general public and it serves as justification for resorting to unconventional medicines that have never been able to show solid proof of efficacy; but we see that it still persists among the medical profession.

To know whether the placebo effect is real or should be relegated to the same category as poltergeists, it will help to go back in history.

cartoon

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Posted in: Clinical Trials, Science and Medicine

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