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When fraud undermines science-based medicine

The overriding them, the raison d’être if you will, of this blog is science-based medicine. However, it goes beyond that in that we here at SBM believe that science- and evidence-based medicine is the best medicine. It’s more than the best medicine, though; it’s the best strategy for medicine to improve therapy for our patients. We frequently contrast science-based medicine with various forms of “complementary and alternative medicine,” specifically pointing out that SBM changes its practices as new science and new evidence mandates it while CAM tends to rely on ancient, vitalistic, pre-scientific or pre-modern scientific beliefs about how disease occurs as the basis for its therapies. Although it may be painfully slow and frustrating at times and even though there may be major stumbles along the way, the overall course of SBM over the last century has in general been to produce ever more effective therapies and to discard therapies that are either ineffective or whose risk-benefit ratios are insufficiently favorable. The one single most important thing behind the advancement of medicine is good science.

That’s why I really, really hate scientific fraud, and I’m really, really upset, perhaps even more so than Dr. Atwood, over the discovery last week of what is arguably one of the most massive scientific frauds in medical history. It doesn’t matter that Dr. Atwood is an anaesthesiologist and I am not, meaning that the specific scientific fraud unearthed, which was perpetrated by an anesthesiologist studying multimodal anesthesia, as reported in Anesthesiology News, the Wall Street Journal, and the New York Times. I am a surgeon, and the relief of surgical pain in my patients is an important part of my practice. If the scientific basis of what my colleagues in anesthesiology do before, during, and after my operations is called into doubt, I have to wonder if I am giving my patients the best surgical care. Aside from that, there is the intellectual outrage I feel as a result of seeing science and patients betrayed in such a systematic and blatant manner.
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Posted in: Clinical Trials, Health Fraud, Pharmaceuticals, Science and Medicine, Surgical Procedures

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Scientific Fraud Hits Home

Last week the story broke that Scott Reuben, an anesthesiologist and clinical researcher at Baystate Medical Center in Springfield, MA, had falsified data in at least 21 publications over a period of at least 12 years—making it one of the most enduring examples of scientific fraud in memory. Almost all of Reuben’s papers had reported innovative methods for providing post-operative pain relief (analgesia); many of them involved ‘multimodal’ regimens for painful orthopedic procedures such as spinal fusions and total knee replacements. Recent papers reported regimens that included celecoxib (Celebrex) and pregabalin (Lyrica), both made by Pfizer. Much of Reuben’s research had been funded by Pfizer, and Reuben has been a member of the Pfizer speaker’s bureau (that information is included because the reader would otherwise wonder, but there is no indication that Pfizer has been intentionally involved in Reuben’s fraud).

I will not discuss this case in detail; look for a more comprehensive piece on SBM next week. Rather, I present it now to offer a local example of how such a breach of trust affects those who rely on clinical research to inform their care of patients.

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Posted in: Clinical Trials, Health Fraud, Pharmaceuticals, Science and Medicine

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A Medical-Skeptical Classic

The medical literature slowly becomes outdated. As a result there are not that many ‘classics’ in the field, since their content becomes less relevant. The medical aphorism is that 10 years after graduation from medical school, half of everything you learned will no longer be valid. The problem for medical students is trying to figure out which half of their curriculum is not worth learning.

Old studies become increasingly irrelevant as diagnosis and treatment changes over time under the relentless pressure of medicine. I once came across the best of Osler, with his descriptions of typhoid fever and pneumococcal pneumonia. The essays were far more literary in style than today’s journal articles, describing the presentation of these diseases in Dickens-like detail, but of little practical help given the advances in treatment and the understanding of the microbiology of diseases.

Technology also expands and limits what papers are available. If there is not an electronic form of an article, it might as well not exist. Many classic articles are not yet available in digital form, and the article in question for this post I had to get as a scanned version of the original paper, rather than a pdf. As a result of time and lack of electronic access, much of the older medical literature is not easily accessible, and journal publishers are not particularly interested in the free dissemination of information. Which is a shame. There is the occasional older reference that is as applicable today as when it was published. (more…)

Posted in: Clinical Trials, Science and Medicine

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Fakin’ it

Last week the Times of London revealed inside information from the General Medical Council (UK, responsible for physician licensing) of an ongoing investigation of Dr. Andrew Wakefield and from its own investigation. This revelation recalled other instances of fakery from reports of sectarian medicine (“CAM”) successes. The Medical Council information contained evidence that the data from the now famous Wakefield cases used to claim an association of the MMR vaccine with childhood autism and inflammatory bowel disease were misinterpreted, altered, and to some extent, faked. The report and history were reviewed by David Gorski last week. In eight of twelve cases, the dates of autism onset were “rearranged” to fit the needed time association, and many small bowel biopsies were “reinterpreted” to show inflammation.

The Wakefield claims were long suspected by reputable medical scientists and skeptics  as being erroneous or fraudulent.  Note: the Council hearings are still in progress, and the Times report is subject to legal complaint.  The original details can also be seen in the Times articles.

This expose’ adds to a growing list of reports with erroneous and faked information in medical journals used either for economic reward, undeserved fame, or to promote ideological claims for medical sects and cults. Although history of erroneous or false claims goes back hundreds of years, the altering or synthesizing of data passing the recently conceived peer review system is new,  illuminating defects in the journal peer review and editing system.

If journals were invented in the 18th century, and operated like journals of today, Mesmer’s demonstrations might have been published, and the Ben Franklin and Antoine Lavoisier and French Academy’s disproof might have been rejected. (Laughter here.) But journals continue to make major goofs in publishing implausible results despite the popularity of a famous specialty journal for that purpose.

Examples vary from acceptance of language manipulation – “alternative,” “healing,” “integrative,” etc., to the fakery of recent papers showing effects of prayer. The two famous studies of prayer in the cardiac care unit ranged from the unadmitted breaking of the blind in the Bird study (So Med J 1988; 81:826-826) to unadmitted imbalances of subject and control groups (Harris, Arch Int Med 1999;159:2273-2278.) And from those to the likely fakery of the distant prayer study of in vitro fertilization (Cha, Wirth, Lobo; J Reprod Med 2001:46;781-786) in which three separate prayer groups on two continents improved pregnancy rates in a group of women on a third continent by an implausible 100 percent. In all of these cases, the papers passed peer or editorial review despite the methodological defects that were picked up by us skeptics (K. Atwood, K.Courcey [an RN] B. Flamm, and others.)

Adding insult to the above, Annals of Internal Medicine published a systematic review of intercessory prayer (Astin et al, Ann Int Med, 2000;132: 903-910) containing not only the Bird and Harris studies counted as positive, but also the Targ study on brain tumors, found by reporter Po Bronson to have had its end point altered by the authors when the primary one showed no effect.
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Posted in: Basic Science, Clinical Trials, Faith Healing & Spirituality, Health Fraud, Medical Academia, Science and Medicine, Vaccines

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Comparative Clinical Effectiveness Research: Good News In Shades Of Gray

When I first heard about the new emphasis on comparative clinical effectiveness research (CCER) in Obama’s economic stimulus bill I thought, “Thank goodness! Maybe now science will truly regain its rightful place and we’ll end the CAM, ‘me-too’ drug, and excessive-use-of-technology madness that is wasting so much money in healthcare.” In fact, I was so excited about the new administration’s apparent interest in objective analysis of medical treatment options, that I intended to write a jubilant blog post about it. However, as with most things that seem black and white at first glance, further analysis reduces them to shades of gray.

What Is Comparative Clinical Effectiveness Research?

The new economic stimulus bill, also known as The American Recovery and Reinvestment Act (ARRA) includes 1.1 billion dollars for clinical comparative effectiveness research. Interestingly, CCER is not defined in the bill though AHRQ describes it this way in their glossary:

“A type of health care research that compares the results of one approach for managing a disease to the results of other approaches. Comparative effectiveness usually compares two or more types of treatment, such as different drugs, for the same disease. Comparative effectiveness also can compare types of surgery or other kinds of medical procedures and tests. The results often are summarized in a systematic review.”

Any mention of “comparative cost effectiveness” or value-based language is notably absent.

How Does It Work?

The government’s new CCER initiative will be administered through a Federal Coordinating Council for clinical comparative effectiveness research. The FCC consists of a group of 15 federal employees, half of whom “must be physicians or other experts with clinical expertise.” [Meaning, none have to be physicians.] Some have suggested that the FCC is the first step toward an organization modeled after Britain’s National Institute of Health and Clinical Excellence (NICE). NICE is regularly tasked with helping the NHS to decide which medical treatments should be available to their beneficiaries, and which should not be covered (based on their efficacy and cost).

The budget for the CCER will be divvied up as follows:

400 million – left to the discretion of the Secretary of HHS with 1.5 million to go to the Institute of Medicine for a report regarding where to focus CCER attention initially
400 million – to the office of the director, NIH
300 million – to AHRQ

Here is a quote from the ARRA bill, discussing the mechanics of CCER:

“The funding appropriated in this paragraph shall be used to accelerate the development and dissemination of research assessing the comparative clinical effectiveness of health care treatments and strategies, including through efforts that: (1) conduct, support, or synthesize research that compares the clinical outcomes, effectiveness, and appropriateness of items, services, and procedures that are used to prevent, diagnose, or treat diseases, disorders, and other health conditions and (2) encourage the development and use of clinical registries, clinical data networks, and other forms of electronic health data that can be used to generate or obtain outcomes data: Provided further, That the Secretary shall enter into a contract with the Institute of Medicine, for which no more than $1,500,000 shall be made available from funds provided in this paragraph, to produce and submit a report to the Congress and the Secretary by not later than June 30, 2009 that includes recommendations on the national priorities for comparative clinical effectiveness research to be conducted or supported with the funds provided in this paragraph…”

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Posted in: Clinical Trials, Pharmaceuticals, Politics and Regulation, Public Health

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Another challenge to surgical dogma

Better late than never with this one.

The dogma that I’m referring to is the remaining practice of using NG tubes in anyone with upper gastrointestinal surgery (liver, stomach, pancreas, duodenum, proximal small intestine) and then placing a jejunostomy tube (a tube, also often called a J-tube, that goes into the jejunum, or the proximal part of the small intestine, through which feedings can be given). The rationale for this was that the peristalsis of the small bowel returns almost immediately; it’s the large bowel and stomach whose return of peristalsis is delayed. Consequently, liquid tube feedings, it was thought, could be given beyond the point of surgery into the small bowel because if there is one surgical dogma that the evidence generally supports and probably always will, it’s always better to use the gut for nutrition than to use total parenteral nutrition (TPN, or feeding by veins). Moreover, there was evidence that such feedings had a protective effect on the lining of the bowel, preventing a phenomenon known as bacterial translocation, in which bacteria could pass through the compromised lining of the bowel after surgical stress. The price, however, was the placement of a tube into the proximal intestine, a procedure that, while safe, was definitely not without complications, some of which (such as bowel perforation) could be serious and require reoperation.

Challenging this dogma is the largest multicenter randomized study yet looking at this question: Which is better, bowel rest (NPO) and J-tube feedings or just letting the patient eat the next day? The study comes out of Norway1 and involved 453 patients. Blinding, much less double blinding, was, as is the case in many surgical trials, not possible because of the very nature of the question being examined, but other than that the design of the study was about as strong as a surgeon could ask for. Basically, patients were randomized to a routine of NPO and J-tube feeding until flatus indicated return of bowel function versus normal food at will beginning on postoperative day one; the experimental design is summarized below:
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Posted in: Clinical Trials, Science and Medicine, Surgical Procedures

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Yes We Can! We Can Abolish the NCCAM! Part II

Pseudoscience and Dishonesty, continued: “Reliable Information”?

In the previous post, we examined misrepresentations by the late National Center for Complementary and Alternative Medicine (NCCAM) Director Stephen Straus and Margaret Chesney, written in 2006 as a rebuttal to a critical article by Donald Marcus and Arthur Grollman in Science magazine. Here, we continue. According to Straus and Chesney:

Before the establishment of NCCAM, there was no central source of CAM information. NCCAM brings evidence-based information on CAM to the public, practitioners, and researchers. NCCAM disseminates research findings and provides reliable information about commonly used CAM practices through numerous channels, including…its award-winning Web site… NCCAM’s communications program deals with a field that is controversial, that has many critics, and that reaches a public that wants reliable information.

Before the establishment of the NCCAM, there was an excellent source of reliable information about “CAM”: Quackwatch. It continues to be the most comprehensive source of such information.

The NCCAM itself does not provide “reliable information about commonly used ‘CAM’ practices.” Rather, it bends over backward—in some instances making categorically false statements—to portray absurd, dangerous, implausible, or disproved practices as safer and more promising than they are.

Examples follow, but first please consider an implicit yet abundant and compelling piece of evidence that has left several of us (1, 2, 3) scratching our heads since the NCCAM began: each year the Center bestows numerous grants for the purpose of teaching “CAM” (not “CAM research”) to health professionals or for “integrating CAM” into various programs, or for establishing “integrative medicine” centers. For examples, look here. Isn’t this putting the cart before the horse? How can this be viewed as anything other than promoting “CAM”? Consider that Straus and Chesney also wrote:

In the early years of NCCAM, there was a sense of urgency to scientifically assess a range of CAM therapies that had been in long use by the public in the absence of proof of safety or efficacy.

In the subsequent 8 years, there has not been a burgeoning list of “CAM therapies” that have been proven safe and effective. The number of treatments that would qualify for that list, or for a comparable list before the creation of the NCCAM is, if you’ll excuse the rudeness of reliable information,…zero. In other words, the NCCAM admits that the treatments that characterize its “CAM integration” projects have not been shown safe and effective.

But back to a few explicit examples of unreliable information.

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Posted in: Acupuncture, Clinical Trials, Science and Medicine

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Natural versus “natural” in CAMworld

“When I use a word,” Humpty Dumpty said in rather a scornful tone, “it means just what I choose it to mean — neither more nor less.”

“The question is,” said Alice, “whether you can make words mean so many different things.”

“The question is,” said Humpty Dumpty, “which is to be master— that’s all.”

From: Through the Looking Glass, and
What Alice Found There
by Lewis Carroll

“How can I help seeing what is in front of my eyes? Two and two are four.”

“Sometimes, Winston. Sometimes they are five. Sometimes they are three. Sometimes they are all of them at once. You must try harder. It is not easy to become sane.”

From: Nineteen Eighty-Four by George Orwell

One of the most powerful weapons in the armamentarium of advocates of the unscientific and implausible medical practices that fall under the rubric of “complementary and alternative medicine” (CAM) or, even worse, “integrative medicine” (IM), both of which seek to seamlessly “integrate” pseudoscience with science to the point that people start to be unable to tell which is which in order to “complement” effective medicine with placebo-based medicine, is their skill manupulating language. Wally Sampson has harped on this time and time again on this blog, particularly in his masterful fictional (but all too true-sounding) response to the question, “Why would medical schools associate with quackery?” Kimball Atwood has even turned the–shall we say?–”plasticity” with which CAM/IM advocates manipulate language to their advantage into humorous and all-too-infrequently recurring Friday feature. All of us have complained about how CAM/IM advocates have coopted diet and exercise as being somehow “alternative” and are now using that as the “foot in the door” to introduce pseudoscientific quackery like reiki and homeopathy into not just medical schools but to try to persuade the incoming Obama Administration to fund quackery on equal terms with scientific medicine as part of a “reform” designed to “promote health.”

Much of the success, both previous and current, of CAM/IM advocates depends upon language. Just like Humpty-Dumpty, to ideologues like Deepak Chopra, words mean just what they choose them to mean, and, just like the view forced on Winston Smith at the Ministry of Love, two plus two are sometimes five, no matter how much we know they are four. All it takes is viewing science as “just another narrative,” as postmodernist supporters of CAM/IM would like. Once that happens, there is nothing to stop one from viewing CAM/IM as being a “narrative” just as valid as that of science-based medicine. It’s the way “quackery” has been transformed into “unconventional,” later into “alternative,” and most recently “integrative” medicine. It’s all designed to play on the natural American desire to be “fair” and the media’s desire for “balance,” even though it is not fair to give pseudoscience a patina of scientific respectability that it does not deserve or use “balance” to present quackery as though it has equal standing with scientific medicine.

If there is one word that has been corrupted by the CAM/IM movement more than any other, my vote would go the world “natural.” Of course, it’s not just the CAM/IM movement that has molded this word to mean whatever meaning is required for whatever purpose is desired. For decades, the advertising industry has done the same. However, the CAM/IM movement takes it to a new level, or “kicks it up a notch,” as a certain TV chef likes to say.

I came across a perfect example of this in the form of a man named Tony Isaacs.
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Posted in: Cancer, Clinical Trials, Science and Medicine

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Our own slippery grounds

When we were forming the National Council against Health Fraud I wondered aloud to the president, Bill Jarvis, what we would do if society solved the chiropractic problem. Bill laughed and said there would never be an end to quackery claims.

How right he was. But why? Many express surprise that at this time of remarkable intellectual and scientific advance, so many people choose to believe in irrational medical claims. The answer I am used to is the one that explains the difference between the attraction of subjective versus the dryness of the objective; between reflex and conditioned responses and rational thought, and between immediate emotionally gratifying, low-level mid-brain reactions and slow-reacting, cool, higher level intellectual thought. These comparisons are all valid but in trying to answer the question, we can miss the constancy of human nature biology, the dimension of time flow, the changing nature of evidence, and as yet unemphasized, the changes and evolution of measurement.…

Before Evidence Based Medicine (EBM) was devised, and the randomized clinical trial (RCT) accepted as the so-called gold standard, our evidential decisions turned on balances or ratios of science/nonsense, rationality/irrationality, reality/delusion, and an estimate of plausibility/implausibility. We can see now that the concept of EBM introduced a new set of standards to our equations balances – proof by RCT and their derivatives, systematic reviews (SRs). The demand for proof by RCT and and SR relegated the previous standards, the unbalanced ratio concept, to the level of anecdote and “uncontrolled observation.” We had to start over again with a new standard.
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Posted in: Basic Science, Clinical Trials, Health Fraud, Science and Medicine

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Psychological support and breast cancer – again

Does the degree of efficacy is depend on the time at which it is measured? Apparently so. The case of psychological support and breast cancer longevity again.

After an original 1989 report of positive effects on metastatic breast cancer, by 2006- 7 the majority of RCTs on such effects had settled the issue in the negative. This was only after 20 years of repeated research grants and RCTs based on hunches and feelings that somehow emotional support really affected the course of cancer. Investigations continued despite analyses showing the few original positive studies had been so flawed in design or defective in reported details, that they should have been dismissed and perhaps excluded from systematic reviews. (Spiegel D, Bloom JR, Kraemer H, Gottheil E. Psychological support for cancer patients, Lancet ,1989 Dec 16;2(8677):1447., Fawzy FI, Fawzy NW, et al. Malignant melanoma. Effects of an early structured psychiatric intervention, coping, and affective state on recurrence an survival 6 years later. Arch Gen Psychiatry. 1993 Sep;50(9):681-9.)

But to advocates, conflicting results served as motive to prove the claims by repeating the studies for 20 years, “doing them right this time.” As of mid-2008, consensus was the issue was still “negative.” Now another study, claimed to be positive, makes the news.

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

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