If there's one thing that proponents of "integrative medicine" (or, as it's been called in the past, "complementary and alternative medicine," or CAM) take great pains to emphasize whenever defending their integration of prescientific and pseudoscientific medicine into medicine, it's that they do not recommend using "alternative medicine" instead of real medicine but in addition to real medicine. Indeed, even the "gods" of integrative medicine, such as Barrie Cassileth at Memorial Sloan-Kettering Cancer Center, not only emphasize that but actually often take umbrage when it is suggested that integrative medicine advocates ever suggest that alternative medicine should be used instead of science- and evidence-based medicine. She's even written articles attacking cancer quackery, seemingly oblivious to the fact that many of modalities that fall under the rubric of integrative medicine are based on the same mystical or pseudoscientific ideas that the quackery she decries is.
Certainly, that's what I thought about Glenn Sabin. You might remember Glenn Sabin because he's been featured right here on this very blog a few times over the last several years. For instance, his admission that integration medicine is a "brand, not a specialty," served as the basis for my discussion of the evolution of integrative medicine as a concept. More recently, he declared that CAM is dead and that "evidence-based, personalized integrative medicine continues its ascent," and still more recently he wrote an ebook listing what he considered to be the 125 milestones in the development of integrative medicine. Through it all, if there's one unerring talking point that proponents of integrative medicine never abandon, it's that message that the woo is supposed to complement real medicine, to be "integrated with real medicine" and not to be used in place of it. Sabin promoted this message himself. Unfortunately, now he's gone one step beyond with his new book. In it, he has co-opted "N-of-1" trials to promote his message, using them not as an experimental method whose usefulness is not yet sure but rather as a slogan for integrating quackery with medicine.
I was actually surprised—but perhaps shouldn't have been—when I discovered that Sabin has what is in essence his very own alternative cancer cure testimonial. I really don't know how it could be that I didn't know this before. To be honest, I'm a little embarrassed that I didn't know, but now I do, thanks to his new book alluded to in his other book about the milestones of integrative medicine. That book is entitled N-of-1: One man's Harvard-documented remission of incurable cancer using only natural methods. I recognized immediately that this is not a book about an "N-of-1" clinical trial (an interesting topic for another day), but rather a book describing an alternative medicine cancer cure testimonial co-opting a hot new area of clinical trial research.
Given the number of such stories that I"ve deconstructed in the past, I couldn't let this one pass without examining it more closely, particularly given that it features quotes by Lee M. Nadler, MD, on how he has "witnessed an extraordinary patient who achieved a clinical response through non-conventional treatment approaches" and by David Rosenthal, MD on how Sabin "understands the importance of the mind and body in reducing stress and improving overall clinical outcomes in cancer. We are pleased to be able to work with him.” Both, of course, are Harvard faculty. I even took advantage of the ability to download an excerpt from the book. Because it required me to provide an e-mail address, I used a throwaway.
Here's the blurb on his website:
In 1991, Glenn Sabin was a 28-year-old newlywed diagnosed with chronic lymphocytic leukemia (CLL)–a disease doctors called “uniformly fatal.” Treatments could buy him some time and eventually ease his discomfort, but there was no conventional cure. Glenn’s prognosis was clear: he was going to die.
Although Glenn and his wife, Linda, continued to consult with doctors, cancer specialists and top oncologists, Glenn made a monumental decision: he would become his own health advocate. While he continued to “watch and wait,” Glenn would figure out how to stay alive.
No one could predict when a large-scale clinical trial would discover a cure for CLL, so Glenn began his own, medically monitored and carefully researched lifestyle changes. He would conduct his own, single patient clinical trial.
He would become an “n of 1.”
Today, Glenn is not only alive, but a 2012 biopsy at Harvard confirmed that his bone marrow contains no leukemic cells. His case is now part of the medical literature.
I was glad to see that this case was part of the medical literature in the form of this case report now, because it gave me a far better account than I usually get upon which to base my discussion. So I headed straight to the source to check out this case report and was actually a bit surprised to notice that one of the authors is someone I knew, albeit not well. I also noticed that the authors included Jeffery White, Director, Office of Cancer Complementary and Alternative Medicine, National Cancer Institute. (That's OCCAM, an office that has a budget approximately as large as that of the NCCIH.) The first author is someone named Dawn Lemanne, who is affiliated with Oregon Integrative Oncology. Let's just say that this is not a particularly evidence-based practice.
So what does Sabin claim? Basically, he claims that his "natural therapies" resulted in his remission from CLL, not once, but twice. In 1991, Sabin was diagnosed with CLL and underwent a splenectomy because they lymphocytes had infiltrated his spleen. It was noted that, after his splenectomy, from 1992 to 2003, From 1992 to 2003 Sabin remained asymptomatic, but serial bone marrow biopsies revealed increasing lymphocytic infiltration. During this period, the peripheral white blood cell count fluctuated between 5.3 and 14.8 g/dL. Also, in 1993, Sabin did this:
Meanwhile, in 1993, at age 30, the patient began a self-directed health regimen. This included a near-vegetarian diet with occasional seafood, filtered water, over-the-counter nutritional supplements, and exercise (mainly resistance training with some aerobic activity consisting of power walking). He avoided processed foods and obtained organic or unsprayed produce whenever possible.
So, while Sabin was undergoing this self-directed health regimen, his numbers were getting worse. This is not particularly good evidence supporting the efficacy of diet and exercise for curing CLL. In fact, in 2003, Sabin developed fever, malaise, night sweats, and fatigue. Basically, he developed a relapse of his CLL and treatment with steroids, rituximab, and cytotoxic drugs was recommended. He declined, and amended his supplement regimen to include conjugated linoleic acid, whey protein with lactoferrin, and the botanical extract artemisinin. This is how the testimonial goes after that:
Despite feeling poor, he walked and swam daily. By October 2003, a few months after the episode began, the hemoglobin had risen to a normal value of 13.4 g/dL. The constitutional symptoms abated, and the patient made a complete clinical recovery.
In May 2006, when the patient was 42, a bone marrow examination showed lymphocytic replacement of 30%. This was decreased compared to the 2003 examination during the hemolytic anemia episode when lymphoid aggregates had replaced 90% to 100% of the marrow.
So, over three years, he got better, but not completely better. Three years later, in 2009:
In December 2009, the white blood cell count rose to 17,500/µL, with a lymphocytosis of 63%. Hemoglobin was 13.6 g/dL, and platelets measured 293,000/µL. The patient, now age 46 and asymptomatic, consulted author KB.
Based on early-phase clinical trials showing the efficacy of epigallocatechin-3 gallate in chronic lymphocytic leukemia, author KB prescribed a supplement formula containing reishi mushroom (Ganoderma lucidum), chaga mushroom (Inonotus obliquus), and green tea (Camellia sinensis) . This formulation was chosen because the green tea fraction provided approximately 1200 mg daily of epigallocatechin-3-gallate.
In addition to this directed anticancer treatment, the patient’s constitutional resistance to cancer progression was assessed via detailed testing of inflammation and glucose metabolism. High-normal fibrinogen levels and modest elevations in D-dimer and C-reactive protein were interpreted as signifying hypercoagulability and mild generalized inflammation. Although levels of insulin, blood glucose, and fructosamine were normal, C-peptide was above ideal at 5.3 ng/mL, suggestive of aberrant glucose metabolism. In addition, 25-hydroxy vitamin D was 46.7 ng/mL, slightly below the optimum range of 50 to 70 ng/mL.
To address these issues, the patient was placed on high-dose fish oil containing eicosapentaenoic acid (10.8 g) and docosahexaenoic acid (2.4 g daily), curcumin (4 g daily), vitamin D3, Scutellaria baicalensis, and probiotics. Calcium and magnesium were added to address a reported decrease in lumbar vertebral bone density.
Despite this approach, by October 2010, the white blood cell count had reached 47,800/µL, with lymphocytes at 81.6%. At this time, author BRK detected an immunoglobulin variable region heavy chain (IgVH) mutation in the peripheral blood by PCR.
So basically what is clear is that the woo wasn't working. Sabin was slowly getting worse. At least, his laboratory values were slowly deteriorating. His CLL was still active. Then this happened:
In December 2010, author KB increased the dose of epigallocatechin-3-gallate to 4 g daily, basing the dose on that used in a clinical trial at Mayo Clinic .
In February 2011, two months after the patient began the higher dose of epigallocatechin-3-gallate, the white blood cell count peaked at 50,600/µL, with 84% lymphocytes. Fibrinogen, D-dimer, C-reactive protein, and C-peptide levels had dropped to low-optimal ranges. The vitamin D level had reached a supranormal level of 110 ng/dL, and the dose of supplemental vitamin D was decreased.
In March 2011, the white blood cell count had dropped, measuring 30,600/µL. By August 2011, the white blood cell count was 6800/µL, with a lymphocyte fraction of 49%.
In January 2012, when the patient was 48, a marrow examination at the Dana-Farber Cancer Institute demonstrated slightly elevated cellularity at 60%. However, lymphocytes represented only 5% to 10% of the cellularity. Flow cytometry of the aspirate also showed no evidence of a lymphoproliferative disorder. These findings were interpreted as being inconsistent with a lymphoproliferative disorder.
In September 2014, when the patient was 51, the marrow was hypercellular at 80%. However, lymphocytes again comprised only 5% to 10% of the cellular component. Of particular note, these lymphocytes were specifically tested and found to be predominantly CD3 positive T cells, whereas B cells would have been consistent with chronic lymphocytic leukemia. For a second time, flow cytometry of the aspirate showed no molecular evidence of a lymphoproliferative disorder. IgVH mutation was no longer detected on PCR. The entire study was interpreted as being without evidence of a lymphoproliferative disorder.
So let's get this straight. The patient's white blood cell count kept increasing after Dr. Block increased the dose of epigallocatechin-3-gallate. It kept increasing for two full months and peaked at a pretty impressively high level. Then it decreased some and took a total of eight months after the dose change to decrease to a level within normal parameters. A year later, he appeared to be in remission, but even more than three years later, although there didn't seem to be molecular evidence of a lymphoproliferative disorder, Sabin's lab results can't be said to be exactly normal. Yes, in 2015, three years after his last flare-up followed by a seeming remission, Sabin is doing well. I hope he contineus to do well.
Unfortunately, this testimonial is thin gruel to attribute Sabin's good fortune to any sort of "natural" regimen that he undertook. After all, the first time around in 1992, he did a radical lifestyle alteration, but it clearly didn't impact the course of his disease over more than a decade. Similarly, his later experiences don't demonstrate that epigallocatechin-3-gallate or any of the other woo that Sabin undertook is the cause of his remission, no matter how much Sabin and the authors of the article describing his case report want to make it so. Correlation does not equal causation. It can indicate causation, but quite frequently it does not. Basically, this whole case report is singularly unconvincing.
I learned right away why I should be skeptical of this testimonial right from the very beginning of the case report:
Clinical remission of chronic lymphocytic leukemia without conventional therapy is a rare event, estimated to occur at the rate of 1% per year among cases of CLL . Moreover, most such remissions are incomplete; a recent review of 21 such cases found persistent monoclonal B lymphocytosis in 67%, with only 33% regressing to a molecularly normal phenotype
So right away, we know that approximately 1% of patients per year with CLL will undergo spontaneous remission and that around 33% of those patients will completely regress to the point where molecular techniques can't find any cancer cells. We also know that one publication has listed 21 such cases, of which seven were complete molecular remission. In other words, if these figures are accurate a grand total of around 0.3% of patients with CLL per year will undergo a complete molecular remission. that's 3 out of 1,000. Admittedly, that's a low number, but I wouldn't call it so low as to be so out of the ordinary that most likely explanation for why Sabin has done well over the last quarter century must be the woo that he indulged in. A more likely explanation is that he was one of the 3 in a thousand (or one in a thousand or even lower if you think his chances of a spontaneous remission were lower because his young age and splenic involvement with CLL, which usually portends a more dire prognosis. None of this is to say that the epigallocatechin-3-gallate couldn't have had an effect. Clearly, it might have, What I am saying is that Sabin is far too confident that his use of alternative medicine and integrative therapies were the cause of the remission of his cancer, particularly given that, according to the case report, Sabin remained asymptomatic throughout his entire course over 25 years, with the exception of the times he had his two relapses.
So one has to ask oneself when confronting a testimonial like this: What is more likely, that Sabin cured himself with lifestyle and by increasing the dose of one supplement or that he was lucky, one of the handful of patients who were fortunate enough to have a complete remission with no molecular signs of the tumor? While it is possible that Sabin's interventions might have impacted his cancer in a positive manner, this testimonial isn't particularly strong evidence of that. The timing isn't as compelling as it's sold, which is this way in the introduction to Sabin's book:
When I was diagnosed with chronic lymphocytic leukemia in 1991, most doctors
would have said that modern medicine had no cure.
Most doctors believed then, that finding effective cancer treatments required huge sums of money to be spent on randomized controlled trials, in which expensive pharmaceuticals, many with harsh side effects are tested on numerous human subjects over many years. Such undertakings require the concerted efforts of exquisitely trained, well-funded, and very persistent scientists.
Most doctors believed then that nothing I could do for myself would help me survive leukemia. Although diet, supplements, and exercise—the pursuit of good health—might make my body stronger, my lifestyle choices would have no effect on the leukemia, and would therefore be a waste of time and money.
In 1991, most doctors would have said that there was no way I could successfully treat my own cancer, at home.
It is now 2016, and I am alive. And although I am well, very well indeed, many physicians still say that a patient cannot successfully treat cancer at home. However, perhaps it can be done. Perhaps I have done it. I don’t know. This book is my story, and it is above all the story of an experiment. As an experimenter I have catalogued my failures as well as my successes, in hopes that interested readers might find some instruction in both.
I note that I can't evaluate Sabin's cataloguing of his successes and failures for the simple reason that the book excerpt he sent me was only the first few chapters that described his initial diagnosis. It's compelling reading, the story of a young man recently married who was diagnosed with a chronic disease excepted to be lethal, but it doesn't really provide any details. I also note this case report of a spontaneous remission of CLL, in which there was no apparent triggering event and the authors noted that "even after the complete spontaneous clinical and laboratory regression of the disease, there were still occult CLL cells in the remaining microenvironmental niches of the bone marrow that could be detected by molecular techniques." Again, I hope Sabin continues to do well. I really do. However, there's a good chance he still has leukemic cells lurking at a level that is currently undetectable.
I discussed Sabin's case for a simple reason. Sabin is one of the leading lay popularizers of "integrative medicine." He is in big time with many of the leading integrative medicine physicians, as evidenced by the blurbs they provided for his book and the quotes of praise by them on Sabin's website by luminaries such as Drs. Jun Mao, Debu Tripathy, Mark Hyman, David Rosenthal, Lorenzo Cohen, Moshe Frenkel (who's affiliated with M.D. Anderson and into homeopathy and co-authored a study testing homeopathic remedies on breast cancer cells), and others. Yet, clearly he believes that alternative medicine probably cured him of a fatal disease and has published a book documenting that process based on his "N-of-1" self-trial. In reality, his "N-of-1" is not a clinical trial, Sabin's use of the term notwithstanding. There was no predetermined protocol, and his story shows none of the hallmarks of a real N-of-1 trial. Basically, Sabin's story is nothing more than, at best, a case report, but, as told on his website, an alternative cancer cure testimonial masquerading as an "N-of-1" trial.
In this, he is little different from Suzanne Somers, Chris Wark, a Stanislaw Burzynski patient, or any number of believers in medical pseudoscience who use their testimonial of survival as evidence that quackery works. Sure, Sabin is less quacky than Somers or Wark, and—who knows?—maybe green tea extract has effects against CLL, but, whatever denials he might make otherwise, his book is selling the message that you don't necessarily need conventional medicine to treat cancer, that you can treat your cancer on your own with "natural" methods. That's a message that's bound to lead to preventable deaths. It's also counter to the number one talking point of integrative medicine in general and integrative oncology in particular: That alternative medicine should be used with medicine and not as an alternative to medicine. It's a premise that is belied by the embrace of naturopathy by integrative medicine, given how naturopaths frequently substitute quackery for real medicine.
Finally, you can see the way "integrative oncology" is going by this description of Sabin's co-author, Dawn Lemanne, MD, MPH:
Dr. Dawn Lemanne is a practicing oncologist and integrative medicine authority. One of a small but growing number of oncologists integrating conventional and complementary therapies to treat cancer, Dr. Lemanne approaches each patient as an n of 1. Her practice draws patients from around the globe.
Dr. Lemanne is a proponent of rigorous single-subject research design development and is active in the quantified self movement. The first medical oncologist to serve on the faculty of New York’s Memorial Sloan Kettering Cancer Center’s integrative medicine service, she currently teaches physicians in the University of Arizona’s flagship integrative medicine fellowship. She is the author of peer-reviewed scientific articles, textbook chapters, and works for the popular press. Dr. Lemanne speaks by invitation domestically and internationally.
After earning the MD degree at the University of California, San Francisco, Dr. Lemanne trained in medical oncology at Stanford University and in integrative medicine at the University of Arizona. She also holds advanced degrees from UC Berkeley and Johns Hopkins University.
Rigorous? I'd hardly call the case report on Glenn Sabin that I just examined rigorous.
Clearly, since most integrative medicine modalities fail in rigorous randomized clinical trials, this is the way the specialty is going, both because "N-of-1" trials can be sold as evidence that the woo being integrated into medicine works without the need for all those pesky expensive rigorous randomized trials and because N-of-1 trials cater to the very core beliefs of CAM and integrative medicine. After all, integrative medicine is based, above all on catering to "special snowflakes." Its proponents claim to treat each patient as an "individual" and to treat the "whole" person, and N-of-1 trials make it all about the individual patient and move medicine away from rigorous science and back towards pre-clinical trial medicine, in which anecdotes and case reports ruled. It's all of a piece with how integrative medicine "turns back the clock" on medicine. Yes, there is a role for "N-of-1" trials in conventional science-based medicine, but it's still controversial how useful and rigorous they can be, when and under what circumstances they should be used, and how they should be designed. Unfortunately, Glenn Sabin is showing integrative medicine the way to put the cart before the horse and make "N-of-1" the slogan for integrative medicine.
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The pressing need to better convert anecdotes beyond case histories to "n=1 trials", as a re-useable dataset is better sampling, expanded markers and testing, better record keeping and exhaustive detail reporting in the appendix (ahem).
It doesn't take a brain surgeon (or a rocket scientist, which I arguably am) to see that a research plan that is both "rigorous" and "single-subject" is likely to be not even wrong.
A question for those more knowledgeable than I about pre-med and medical school curricula: Are would-be MDs required to acquire any background in statistics? As a physics major I was required to learn some basic statistics (not a full course, but enough to understand statistical mechanics and thermodynamics) as an undergraduate. One of the basics we learned was the Poisson distribution, specifically that for a Poisson distribution of N events the standard deviation is sqrt(N). For N=1, that means sqrt(N)=1. To put it in layman's terms: if you have only one event, you cannot tell whether you were lucky to see that one event or unlucky not to see a second. The distribution is obviously not symmetric for small N, but if you have one event, an occurrence rate of effectively zero is not ruled out at the 95% confidence level.
In his opening sentence Orac says:"“integrative medicine” (or, as it’s been called in the past, “complementary and alternative medicine,” or CAM)."
I know some folks like to obfuscate the issues by imaginative word play, but CAM is still called CAM (I use the term 'camistry). That is essential, important, vital if patients are to be properly informed and avoid eating cow pie mixed with their apple pie (unless that is what they like.
The issue is one of professional integrity and honesty. The 'IM' quacks can quack all they like, but we do not need to echo their quacks.
No correction is needed.
I was rather irritated by your accusing me of "quacking" like integrative medicine quacks, but then it occurred to me: You seem to be far behind the times regarding the language of "CAM" or "IM" (or whatever the nom du jour is). It is true that the term "CAM" is still used, but it is very much on the way out in integrative medicine circles. The most recent prominent example was when the National Center for Complementary and Alternative Medicine (NCCAM) changed its name to the National Center for Complementary and Integrative Health (NCCIH) two years ago:
The change in name has been very deliberate, with the progression going from alternative medicine to CAM to integrative medicine:
I even discuss this evolution in pretty much every talk I give on integrative medicine. (I'll even show you the humorous slide I use to illustrate the evolution if you want.) The reason for the evolution is to get rid of the word "alternative," which implies "not real medicine." As I point out in the post above, although they tolerate it many IM advocates also don't like the word "complementary" that much either, because it implies that IM is inferior to real medicine and thus not really necessary, useful only as the "icing on the cake," In fact, the next stage in the evolution of language comes from advocates and centers that argue that "integrative medicine" doesn't really describe what CAM/IM does. Their preferred term? "Integrative health." I might have to do a post on that.
Yes, we do still sometimes call it CAM because "CAM" is an easy, pithy abbreviation. Even I slip back into old habits and use the term "CAM" sometimes. However, IM practitioners and advocates (like Glenn Sabin) have been very consciously moving away from the term towards "integrative medicine" for at least a decade now.
As I said, you need to keep up with the times and the language before accusing me of "quacking" like integrative medicine practitioners.
'Keeping up with the times' does not mean acquiescing with the dictates and marketing strategies of those with products to sell, or fantasies they wish to impose on the gullible public.
I had though SBM (and Orac) was above that.
Changing an institution's name does not change the fundamental ideology it propounds.
Why should the mass of general public, to say nothing of scientists, orthodox doctors and the media in general, use terms preferred by, well, quacks?
Seriously? That's your argument? That we shouldn't be "acquiescing with the dictates and marketing strategies of those with products to sell, or fantasies they wish to impose on the gullible public"? I can understand and partially agree with that argument, but come on now. Don't you realize that by using the term "CAM," by your own standard you are doing exactly that? The reason is that CAM is a term invented by the quacks to make what was then alternative medicine seem less threatening and dangerous to doctors and the general public. Again:
Let's take a trip back in time to the mid-1990s, possibly slightly earlier. The term "CAM" was adopted by proponents of what was then called "alternative" or "unconventional" medicine (or even "quackery") as a "marketing strateg[y] of those with products to sell, or fantasies they wish[ed] to impose on the gullible public." By using the term CAM, you're doing exactly what you accuse me of, only you're ten years behind the times, because CAM is a term invented by quacks back in the 1900s to make alternative medicine sound more acceptable to the public and to the medical profession in general. You can use the term if you like, but if you think that by choosing to call it "CAM" instead of "integrative medicine" you're doing anything but buying into the language of quackery, you're basically deluding yourself. The two are the same thing, and both terms were invented by quacks to make that thing more palatable.
My preferred strategy is to use the same terminology the advocates prefer to use but explain each and every time why it's a linguistic sleight-of-hand, usually by mentioning how "integrative medicine" means "integrating" pseudoscience and quackery with real medicine. In fact, that's the very thing I did in this post by pointing out that Sabin's use of the term "N-of-1 trial" was deceptive because what he is describing is not an "N-of-1 trial" but an old-fashioned alternative cancer cure testimonial.
You can disagree with my strategy if you like, but I will not take your sanctimonious accusation of "quacking" like IM practitioners lying down. If you feel that I've somehow "failed" to live up to some standard you have, well, I really don't give a rodent's posterior. You can do it your way, and I'll do it mine.
Orac, a misunderstanding. I have never suggested you are a quack.
Far from it.
I wholeheartedly support all attempts to expose the semantic sophistry and shenanigans of those that are.
I note you say "...both terms were invented by quacks to make that thing more palatable", but what is 'that thing'?
What term should we use to describe outmoded modalities of treatment which have no basis in reality and no plausible evidence of any benefit on patients beyond those which are due to context and placebo effects? And which require in their practitioners an alternative mind-set to that which is conventional? (a belief in vitalism etc.) And which are used by their practitioners as complements to orthodox treatments? I prefer to think of these modalities as 'condimentary', as they provide flavour to a treatment programme, but no substance.
Being dragged into the 'camp' of those who claim such modalities can be usefully 'integrated' with conventional care is not helpful to patients who need to distinguish cow pie from apple pie (using Mark Crislip's analogy).
If there is a better term than CAM (or camistry, or condimentary), let's use it. But 'integrative' ('integrated' in the UK) ain't it, never mind the ambitions of quacks.
Let's call a spade a spade.
May the Wu be with you!
That "thing" is combining quackery with medicine and rebranding lifestyle and dietary interventions as somehow being "alternative." Under "CAM" the quackery was "complementary." Under IM, it's "integrative." It's all the same thing, though, whatever the quacks call it.
As I said before, you do things your way, and I'll do things mine.
So, "Integrative" is to be taken to mean, and be shorthand for, "the integration of quackery with conventional medicine".
Now all we need is for patients (and politicians) to properly understand that is what is meant by 'IM'.
A better title for the book would have been. "Better to be lucky then smart; One mans successful pressing of his luck"
Eventually, someone always wins the big lottery....but millions of others never will.
Sorry, but I'd rather go with actual science than take my chances that I'll be the one in 10 million.
I think the need here is greater for an actual hypothesis consisting of an explicitly-outlined and planned intervention. Throwing every naturopathic remedy and the kitchen sink at the patient and seeing what happens obfuscates medical science more than it illuminates it.
Exactly. The reason Sabin's experience isn't an N-of-1 trial is the lack of a pre-existing hypothesis and pre-existing protocol to test that hypothesis. What he's describing is at best an anecdote, and I was actually shocked at how unimpressive and vague the published case report of his experience was.
But but but...it's Harvard-documented.
One person's experience has many events and parameters that are notable and comparable to others experience.
Hopefully, even a failure ending in death has several treatments and regressions of disease, where different segments resent different trial periods and additional diagnostic detail, even as heterogeneous disease changes and progresses.
With more thorough detail and longitudinal data, particularly with comprehensive biomarkers, it becomes possible to do retrospective and real time comparisons for the individual, more relevant and useful than trials today.
Here's another scam (herbal cure for dengue), found on this page
while looking up a fake publisher from Beall's list:
But what about this very advanced cancer which was cured by 21-day water-only fast?
Some cases requires as much as 40 days of water-only fasting.
I see an n=4 here. One is the restrictive diet, two is the supplements, three is the increased supplements, and four is supplements for a long time. So he was 1 for four, and yet he claims the treatments worked.
After reading PRN's posts for a while now, I am finally convinced that he has no idea what he's talking about....
You may recall a story from a few years ago that a researcher at Harvard Medical School got into hot water for spending grant funds on a 419 scam. Harvard has many professors, researchers, and students, and unfortunately, some of them are not so smart.
There was also at least one recent case of a Harvard professor committing research fraud. I'd have to look through Greg Laden's archives for details (he used to work in that department and knew the professor in question).
It's an open secret among academics, at least in the northeastern US, that the quality of undergraduate education at Harvard is not significantly better than what is available at Flagship State University. The one thing you get from Harvard that you don't get from FSU is membership in the Harvard Alumni Association, which has historically been a valuable tool for making connections in the business world (past performance is no guarantee of future results).
To me, those who had spontaneous remission of their CLL are the ones needing to be studied to find out how, despite the continued presence of lymphoproliferative cells (or not for those lucky 33% of those who go into remission) they are not dying from their CLL. Similar in my mind to earlier HIV research into why some people never contracted HIV who should have--who have a receptor mutation that keeps HIV from entering their cells.
This sucking down fish oil like it's water by Sabin--well that's ridiculous.
"'The paper is coming out in a week,' announced Goldhamer during his talk Thursday. 'There’ll be a whole lot more doctors and programs doing this.'"
Here it is. Two unimpressive citations and one "activated water" reply that misspells Goldhamer's name. I can't even find a copy.
Hi Orac. I run a cancer charity - the Grace Gawler Institute. We have to deal with the 1000s of casualties of not only alt/med but complementary med done to extreme and thus negatively impacting medical treatments.
You may be interested that Gemma Bond died over Xmas. She had gone quite for over a year - just like Wellness Warrior.
Laura Bond who has built fame and income around "Mum's Not Having Chemo' is now in an ethical dilemna.
GEMMA BOND DEATH http://www.westannouncements.com.au/obituaries/thewest-au/obituary.aspx…
@ Eric Lund, thanks for the additional info and I know that Harvard is vastly over-rated, hence my sarcastic remark. Alties love to puff up credentials and use them copiously. Where the case report emanated from is meaningless, what matters is the quality of documentation.
In case you think it is worth fixing...
You transposed the c and p here.
"disease excepted to be lethal"
"He declined, and amended his supplement regimen to include conjugated linoleic acid, whey protein with lactoferrin, and the botanical extract artemisinin."
Artemisinin? I wonder how he managed to get that, and have to question whether he did or not. For one thing, artemisinin is not a "botanical extract", but a chemical constituent of a plant. Granted, it could be isolated and purified, although only at some cost. For that reason, I suspect that he took an extract of Artemisia annua, rather than a constituent thereof.
"Based on early-phase clinical trials showing the efficacy of epigallocatechin-3 gallate in chronic lymphocytic leukemia, author KB prescribed a supplement formula containing reishi mushroom (Ganoderma lucidum), chaga mushroom (Inonotus obliquus), and green tea (Camellia sinensis) . This formulation was chosen because the green tea fraction provided approximately 1200 mg daily of epigallocatechin-3-gallate."
Was the content of EGCG really the reason the formula was chosen? When extracts of green tea containing high concentrations of the catechin tannin were readily available from a number of commercial sources at the time, I have serious doubts. In my mind, a more likely scenario is that someone wanted to see the formula used by a cancer patient – regardless of the lack of clinical evidence in its support. Finally, call me picky or even "sciency", but neither reishi or chaga are "mushrooms" but hard-textured wood-rotting fungi. Of course, calling them mushrooms instead of fungi is far more appealing to marketers because in the minds of the masses, the term fungus is strongly associated with disease.
Let's not forget that this "N=1" patient is special, because, well, he's _special_.
After all, he “understands the importance of the mind and body in reducing stress and improving overall clinical outcomes in cancer."
And the book blurb calls it "A special story about resilience and self-efficacy".
This ties into the altie conviction that once having taken matters into your own hands and sticking rigorously to a regiment of diet, supplements and/or purges while commanding your mind to overcome the body's weaknesses, you CAN cure your cancer at home in your spare time, or what's left of it. The weaklings who lack your dedication and rely on evidence-based therapies are dying like flies and must somehow deserve it.
The arrogance of such attitudes is stunning, and disgusting.
Eric Lund @2 "Are would-be MDs required to acquire any background in statistics? "
I can't speak for MD, but for MPH you bloody well have to take statistics! That's at least half of the point of an MPH, is to apply statistics to things that are happening to the *public*.
And at no point in my MPH training (from one of the same institutions as Dr. Lemanne) did any professor ever say anything about "oh, n of one studies are great!" No! It was all about how to calculate how many people you need to study to actually have any power to your calculation. That's for outbreak investigation and intervention assessment.
If all you want to do are n-of-one studies, then you need to give up any pretense to caring or understanding about *public* health, which is the total opposite of n-of-one.
And stop making my degree look bad!
@ Eric #19: I don't know if you meant it this way, but you just essentially called Harvard a diploma mill.
I'm not saying you really meant that, but it was what popped in my head and made me laugh out loud.
@ JustaTech: nurses in Doctorate of Nursing Practice (DNP) programs must take BioStatistics. I don't know of a DNP program that doesn't require it. MSN programs, a mixed bag of nuts. But some BSN programs require them.
I'd love to know if it's standard in medical education. If not, maybe it should be.
one “activated water” reply that misspells Goldhamer’s name.
Ah, a reply from an unqualified fraudster who pimps "Enercel" Activated Water for a living and advertises it through the OMICS-wannabe journals from MedCrave.
Apparently Water Fasting will cure AIDS and tuberculosis! It was in a MedCrave journal, and they'd never publish a fraudulent paper!
It is at least in pre-med and believe it's a standard requirement for med school.
^ Aargh, that should be "for med school acceptance".
But not Herbert Shelton.
Oh, who could have guessed the miraculous "natural" curing of cancer was achieved in a cancer for which spontaneous remission is well documented (really, we should also have another 99 "N of 1" studies summarized as "I tried every natural therapy and still died of cancer").
It seems that these natural cancer cure testimonials only ever regard cancers with either a known rate of spontaneous remission, or a very long tail to the survival curve (even circa 1900, it was known that women who refused surgery for breast cancer rarely but sometimes lived more than 15 years past diagnosis).
You never ever see these testimonials if the cancer was of a type that actually kills 100% of patients inside a relatively brief time period (except some from Burzinski maybe, where the patient died 3 months after making the testimonial).
It's almost like there's a bias toward publicizing extraordinary events. Almost.
Meh. It shouldn't come as any surprise that undergraduate pedagogy is not necessarily the highest priority at research universities. This jibes with my experience, although I was at least fortunate enough to be a student when my alma mater still retained some of its bona fide weirdness.
Have you some references for survival of breast cancer patients without surgery? All the papers I could get say it was always lethal.
Median survival: 2.7 years, all comers. Long tail. 4% alive at ten years.
Thank you David. After 19 years, no survivors.
Yes, but notice that this is a series from more than 80 years ago. There was no mammography, and survival was defined as the time from the onset of symptoms until death. So if you're thinking of using this as an argument that overdiagnosis doesn't exist, it ain't gonna fly because every one of these women had palpable masses—or worse symptoms.
Basically, this means that spontaneous regression is limited to X-ray diagnosed cancers, cancers that differ only from one fourth to on eighth of time in their natural history.
I indulged your off-topic comments briefly. This is your last comment on breast cancer and your obsession and perseveration.
Lighthorse: I'm calling you way too picky about what is a shroom or not.
And prn's comment did contain a kernel of the truth. Not that I like how it's said. What's true is that we can have better models, that will use many covariates, to predict outcomes expected under two or more treatments. No need to babble about 'individualized" unless you are selling stuff. It's just modeling, and it's just estimating. We do this now with markers (covariates), but with more data and fancier model we could do better.
You'll find not N-1 but 50 case reports in Dr Gonzalez's book, published posthumously several months ago.
"Conquering Cancer Volume 1" contains 14 pancreatic cancer case histories (and 36 breast cancer histories), most of whom survived in excess of 10 years after diagnosis on the Gonzalez protocol.
As a long term survivor (25 years) of metastatic cancer to the liver and a patient of Dr Gonzalez all those years I am thrilled to see these compelling reports in publication. Soon there'll be another 50 case reports published.
But I'm sure Orac and others will find reasons to dismiss and disparage these incredible case histories (or ignore the book entirely), as they are much too invested in their almost decade-long project to label Gonzalez as a quack.
100 cases from the files of a doctor who only saw 3 or 4 patients a day - many of whom like myself were coming for follow-ups year after year- would and should not be dismissed by any objective reviewer.
The tragedy - and it truly is a tragedy - is that if people like Orac and his ilk had taken Gonzalez seriously and had engaged with him rather than mocked him his protocol may have gained some degree of acceptance. And many people with cancer would be thriving today - as I am- thanks to the brilliant Dr Gonzalez.
I'm ashamed that you call my state your home, "Herb."
And yes, your claims can be dismissed because they lack any and all real scientific backing.
Perhaps you can explain why his "protocol" failed so miserably when actually tested?
There's a reason Dr. Gonzalez was reluctant to publish more than case reports: His treatments didn't work.
As I mentioned in my previous comments, spontaneous remission and anomalous long-term survival are well documented for many cancers, even with no treatment.
When Gonzalez' treatment was actually tested in a clinical trial, it was found to be even worse than standard of care.
I'm glad you're doing well, but you don't have Gonzalez to thank for that.
Is Herb talking about that protocol for pancreatic cancer where the patients actually died *sooner* and had lower quality of life? Or am I thinking or someone else who's name starts with G?
Bob, Thanks! I was thinking of the study where the Gonzalez protocol involved stuffing patients with supplement pills like a fois gras duck.
n=100 does not impress me much more than n=1. Where are your controls? Your stratification? Matching? Your statistics would have no power at all.
The preceding comments (43,44,45) confirm the extreme arrogance and ignorance of people posting here. You all believe in what I call scientism (or perhaps medical fundamentalism), which is the religious conviction that one RCT, no matter how flawed ( Gonzalez wrote a 600 page book "What Went Wrong" documenting the egregious flaws if not outright fraud that characterized the so-called RCT) outweighs carefully reported case reports on dozens of patients who lived (and still live in many cases) many years beyond their expected demise from advanced cancer.
I can guarantee that if those same patients had survival rates with a pharmaceutical intervention as dramatic as Gonzalez achieved it would have been on the front page of most every paper in the world, with or without an RCT. Or for that matter if my own 25-year recovery from metastatic cancer, with no chemo or radiation, just the Gonzalez protocol, were reported it would raise eyebrows. if not generate headlines.
So apparently no number of successful case reports that Gonzalez could have written up - 500 or perhaps even 1000? would have raised even the slightest curiosity with this crowd. Isn't that the case?
I guess Gonzalez had the dumb luck of having 50 patients who all achieved spontaneous remission (with 50 more spontaneous remissions about to be published in a couple of months), which I think is about as many cases of spontaneous remission that all of medical history has documented. But that's more likely than Gonzalez actually helping people you say. What an absurdity. And you can write that with a straight face.
You remind me of the worst of climate deniers. You're so invested in your worldview, you're so terrified consciously or unconsciously that your paradigm of medicine will be exposed as egregiously flawed and you're so afraid of rejection by your peers, that you blindly reject reason and evidence that contradicts your bias in favor of pure ideology and fanaticism.
(And it's not like you're defending a notable medical success. The war on cancer is the most spectacular medical fiasco in history with almost no appreciable progress after trillions of dollars and 50 years.)
People who knew Gonzalez and his work well like Dr. Juilan Hyman, a distinguished oncologist, Dr. Paul Rosch, Professor of Medicine at New York College of Medicine, Dr. Kilmer McCully, discoverer of the role of homocysteine, and best-selling neurologist Dr. David Permutter, wrote praiseworthy blurbs about his work. But I guess they must all be dupes, no matter how distinguished their accomplishments or how well they knew Gonzalez and his work. And Lawrence must therefore be ashamed of them too, even if they did not live in Maryland. (Perhaps Lawrence you should write to each of them expressing your feeling of shame towards each.)
McCully is quoted on the back cover "...Gonzalez developed his successful protocol for cancer treatment, as illustrated by these extraordinary case studies." Similar comments were made by the other endorsers. But again it wouldn't matter if every eminent MD in the world endorsed Gonzalez. You'd still hang your hat on a worthless RCT.
I sort of feel like the Sodom and Gomorrah story, looking for just one righteous person. My only goal in writing is the hope that maybe one reader, just one, will be open minded enough to explore Gonzalez's work with healthy skepticism, rather than hostility. But I'm not holding my breath.
Herb, what is the mechanism of action by which a coffee enema will cause the death of cancerous cells?
And if you think there has been no progress in the detection or treatment of cancer in the past 50 years you are woefully ignorant. What about all those childhood blood cancers that used to be fatal, and now have a 90% survival with modern, scientific treatment?
What about bone marrow transplants?
What about the HPV vaccine to prevent cancer?
What about all the brand-new immunotherapies on the market?
Where were they 50 years ago?
How many cancer treatments have you research, studied and brought to market? How many public health campaigns have you lead to prevent cancer?
Want to know a secret about cancer researchers? When they find something that doesn't work, they move on. Learn from that failure and keep working. They don't write 600 page books about why it should have worked.
Hi again Herb.
And you are correct, basically no number of case reports will sway anyone here, because science.
Let's look at some numbers. I'm going to pick a random cancer, say...renal cell carcinoma. There are 63,000 cases of this disease a year, including 14,000 deaths, in the United States. The spontaneous remission rate of stage 4 RCC is estimated at about 1%. However, there are only maybe 50 case reports ever published on RCC spontaneous remission, because most such cases simply don't get reported as a standalone publication. But nonetheless, if we assume that the 14,000 fatalities per year accounted for most of the stage 4 cases, we can assume there are about 140 spontaneous remissions of RCC a year, just in the United States. And that's just one cancer.
The null hypothesis then is that Gonzalez was simply extremely motivated, more than most other doctors in the field, to publish every case of spontaneous remission and anomalous survival that he came across. If a pharmaceutical company were marketing a drug based on case reports, we would hit them with the exact same criticisms.
Also, I'd like to add, while a large, well conducted RCT is the gold standard of medical evidence, it's not the only acceptable form of evidence for making treatment recommendations.
Large scale epidemiological evidence is often accepted in the absence of good RCTs. Even case series or non-RCT trials can be accepted in the case of diseases that aren't amenable to an RCT, or if the cases are actually compelling, coupled with a rational mechanism of action.
But case reports like the ones you're referring to, that Gonzalez published, they appear to just be rare but recognized events.
Gonzalez had his entire career to make a compelling case for his treatment - he did not. His supporters will think he was just more concerned with curing his patients' cancer. His detractors think he was a quack who just wanted to make money selling false hope. It's his own fault no one can really tell the difference.
People who knew Gonzalez and his work well like Dr. Juilan Hyman, a distinguished oncologist
Oh come now. Hyman was a retired oncologist who served as a hired witness for Gonzalez after the latter lost his malpractice suit and responded by suing his lawyer. Hyman contributed an affadavit to the effect that one of Gonzalez's victims would probably have died anyway even if she had ignored his advice and tried conventional therapy.
Herb was arsing around here 18 months ago leaving the same trail of stupidity.
That last time, Herb went off on a tangent about ozone therapy as a cure for ebola, citing some podiatrist's fictional account from a predatory publisher.
Gonzalez wrote a 600 page book “What Went Wrong”
I'm going to guess that it was handwritten, in green ink.
I sort of feel like the Sodom and Gomorrah story, looking for just one righteous person.
So you are an Angel of the Lord?* Just saying, this sounds too much like the plot of too many FBI-profilers-hunt-serial-killer movies.
* Rather than a "certified life and wellness coach" who pimps out the Gonzalez scam through "a full service holistic health center".
Some choose to disagree (bolding mine)
Where are your numbers?
That appears to be toast. (See also here.)
You can read the same numbers and say: "although the incidence of cancer in men declined by approximately 2% annually in men from 2004-2013, the cancer death rate (2005-2014) declined only by about 1.5% annually. "
Although the overall figures indicate some success, what is striking is that there was very little progress in recent years despite the explosion of the number of cancer scientists in the last thirty years.
Herb, first off: best wishes for a longer and happier life.
Yeah, whatever, the namecalling refuge of those who cannot comprehend the scientific method, and have to fall back on their own having faith (and then applied to everyone else) to explain everything.
Oh, and then you reference:
I rest my case on that point.
Herb, hey, what if you could imagine yourself back in school, and you were assigned a science project, and you had to design it with adequate controls.
No, seriously, Herb, think about it. Experiments with control groups.
Then get back to us.
I can do science. I can't type effectively, nor proofread.
Gonzalez protocol? You mean the coffee enema-based pseudoscience from that crank Nicholas Gonzalez?
Pass thanks. I fail to see how shooting coffee up your bum can cure any cancer and I certainly won't be trying it on mine.
Hmm. Seems that Herb is just reinforcing the difference between science and quackery.
The former is based on evidence. The latter is based on a belief system (which explains his "Angel of the Lord comment.")
Daniel are you really claiming "little progress" when over 2 million people are alive today who wouldn't have been 50 years ago? Are you really claiming that progress in finding a cure is measured by the number of people who do research in this subject? Are you really trying to say that justifies quackery and woo?
Please clarify that for me. Is that what you're really getting at?
From 1991 to 2014, the overall cancer death rate dropped 25%,
I credit improved sanitation.
I will always be grateful for Herb for his comment on his previous visit to RI, in which he provided a citation to a paper by Dr Chris Ross (of The Colin A. Ross Institute for Psychological Trauma)
Dr Ross turns out to believe in the Trophoblastic theory of cancer etiology, which Gonzalez used to promote in his eary career until abandoning it himself. He also believes that it is easy to induce multiple personalities, and was known for trying to do so with his own patients; and that he can shoot focused beams of ELF radiation from his eyes, to control the minds of others. He has provided no end of entertainment. I don't know if he is still running his trauma centre in Michigan.
Unfortunately the "Academicians' Research Center" -- the skeezy bottom-feeding bunch of predatory ratbags who ran the "International Journal of Cancer Prevention Research" -- closed it again after the first issue, so we may never know why Dr Ross chose it as the ideal outlet for his insights.
Yeah, but, if you had bothered to read (or even scan) the entire paper, you’d have seen this bit (bolding mine) -
The passage I quoted at #54 is a little clumsy. One thing I’ve learned here at RI is that you have to read the paper, and not just the abstract (and especially not just the money quote from the abstract).
If you pay attention to figure 2 and 3 of the paper you will see that in men, there was a decline in cancer incidence related to three cancers: prostate, lung and colorectum. Although the origin of the recent decline (2008-2013) in prostate cancer incidence is not clear for me (the peak of overdiagnosis occurring before), the decrease in lung cancer incidence is very likely due to tobacco arrest and that of colorectum might be related to detection of polyps (which are not included as cancers). In these cases, one can say that the decrease of mortality is most likely due to prevention, rather than treatment.
In women, these trends are counterbalanced by an increased incidence in breast cancer from 1980 to 2013 related to mammography screening. The effect of this screening on breast cancer mortality is highly controversial, but the mean estimate is 20%. Therefore, a large part of the decrease in breast cancer mortality is due to early treatment, although there is some improvement related to chemotherapies.
I don’t want to deny that there is some progress, but it certainly does not parallel the increase of the institutional efforts. And this is where I disagree with Orac: the presence of quacks in academic institutions is not an indication that they are more virulent, but a further evidence of the collapse of the knowledge industry.
If you pay attention to figure 2 and 3 of the paper you will see that in men, there was a decline in cancer incidence related to three cancers: prostate, lung and colorectum. Although the origin of the recent decline (2008-2013) in prostate cancer incidence is not clear (the peak of overdiagnosis occurring before), the decrease in lung cancer incidence is very likely due to tobacco arrest and that of colorectum cancer might be related to detection of polyps (which are not included as cancers). In these cases, one can say that the decrease of mortality is most likely due to prevention, rather than treatment.
In women, these trends are counterbalanced by a rising incidence in breast cancer from 1980 to 2013 related to mammography screening. The effect of this screening on breast cancer mortality is highly controversial, but the mean estimate is 20%. Therefore, a large part of the decrease in breast cancer mortality is due to early treatment, although there is some improvement related to chemotherapies.
I don’t want to deny that there is some progress, but it certainly does not parallel the increase of the institutional efforts. And this is where I disagree with Orac: the presence of quacks in academic institutions is not an indication that they are more virulent, but a further evidence of the collapse of the knowledge industry.
But 1.5 - 2% is a nice small number that's easy to scoff at. 2.1 million, not so much
You missed the point: if the incidence declined by 2% and the death rate by 1.5%, then this mean that the treatment was less effective than previously.
You missed the point: if the incidence declined by 2% and the death rate by 1.5%, then this means that the treatment was less effective than previously.
If you have numbers showing that the number of quacks has remained constant over the years, post 'em. But I really don't care if quacks are more common today or not. The question I care about is 'how do we get the quacks out?'. Our host does what he does. What do you do about it?
Yea, but that in't what this particular paper says.
The 2%/year decline in incidence was for men. Women rate of incidence was mostly stable.
The 1.5%/year decline in mortality was for men and women combined.
See the bolded part in my #63
And there is the sentence prior to that - "From its peak of 215.1 (per 100,000 population) in 1991, the cancer death rate dropped 25% to 161.2 in 2014."
I don't give two shi+s and a popsicle if the drop is due to prevention, or cure, or both - I say we keep it up.
Concerning the quacks, I don't try to deal with them: you can be sure before talking to them that they are either idiot or dishonest.
For other people, you can only be sure after talking with them.
The curves (male and female) of cancer mortality are almost parallel from 2005 to 2014.
For the number of scientists, type cancer in pubmed and follow the number of papers for each year in the upper right curve. There were 4 fold less papers on cancer thirty years ago. Now consider that the number of authors per paper has doubled. How many years do we need before everybody will be a cancer scientist? Are you surprised if there are idiots among them?
I am a fan of acupuncture its a really great way for me to relax and relieve pain. I also do diet therapy to improve my health. Alternative medicine will always be my choice because I don't like taking drugs or surgery.
Thank you for that N=1 data point, Ms. Armstrong. Fortunately your anecdote is not evidence, and we will ignore it.
Also, you may want to rethink that last thought if you are ever in an accident, get a bacterial infection or come down with an age related disease like hypertension or diabetes. Just saying.