Archive for Clinical Trials

Glucosamine Update

 Stick-and-ball model of the glucosamine molecule (from the Wikimedia Commons, image by Benjah-bmm27)

Stick-and-ball model of the glucosamine molecule (from the Wikimedia Commons, image by Benjah-bmm27)

Osteoarthritis, the “wear-and-tear” type of arthritis, affects a great many of us as we grow older. Knee pain is a common symptom. The diet supplements glucosamine and chondroitin have been proposed as a more “natural” treatment than pharmaceuticals, and they are components of a number of proprietary “joint health” formulations like Osteo Bi-Flex. The GAIT study (Glucosamine/Chondroitin Arthritis Intervention Trial), compared glucosamine, chondroitin, a combination of the two, and a pharmaceutical (celecoxib) to a placebo in patients with knee pain from osteoarthritis. The only one that worked better than placebo was celecoxib. I wrote about the GAIT trial in 2008. The study was reported in the media as both negative and positive. The positive reports emphasized the subgroup analysis: in one of ten subgroups, patients with moderate to severe pain, the combination of glucosamine and chondroitin outperformed placebo. But in the subgroup of patients with mild to moderate pain, it did not. The authors themselves commented that their study was not powered to draw any conclusions from subgroups and that further studies would be required. (The “power” of a study is a measure of its ability to show an association or relationship between two variables if such a relationship exists.) Now a further study with sufficient power claims to have confirmed the subgroup findings. This may encourage some people to try glucosamine/chondroitin, but I remain skeptical.


Posted in: Clinical Trials, Herbs & Supplements

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A Scientist in Wonderland

Edzard Ernst is one of those rare people who dare to question their own beliefs, look at the evidence without bias, and change their minds. He went from practicing alternative medicine to questioning it, to researching it, to becoming its most prolific critic. I have long admired his work, and I finally met him in person when we were invited to speak at the same conferences. He shattered my stereotype of the stern, formal, self-important German “Herr Professor Doktor.” He was affable, unassuming, and funny; he was even a jazz musician. I wished I knew more about his history, and my wishes have been granted in the form of his new autobiographical book, A Scientist in Wonderland: A Memoir of Searching for Truth and Finding Trouble.

This is a well-written, entertaining book that anyone would enjoy reading and that advocates of alternative medicine should read: they might learn a thing or two about science, critical thinking, honesty, and the importance of truth.

This is a well-written, entertaining book that anyone would enjoy reading and that advocates of alternative medicine should read: they might learn a thing or two about science, critical thinking, honesty, and the importance of truth.

Edzard Ernst, the early years

Dr. Ernst was born in post-war Germany; his family had suffered greatly during the war and his uncle had been a general in the Waffen SS. He felt slightly ashamed to be German, and as a result he researched and wrote about Nazi health beliefs and medical atrocities so the history of their misdeeds would not be forgotten.

His father was a doctor, his mother an enthusiastic devotee of alternative medicine who subjected him to homeopathy, ice cold baths, and barefoot walks at dawn through wet grass. Early in life, Ernst began to manifest a tendency towards doubt and irreverence, along with an irrepressible sense of curiosity.

Music was his first love. He earned good money when he and his friends spent their summer vacation busking on the beach at St. Tropez, and he had been seriously considering a musical career until his mother persuaded him to study medicine. He earned an MD in Germany, in an environment where alternative medicine was unquestioningly integrated with mainstream medicine. He received hands-on training in acupuncture, autogenic training, herbalism, homeopathy, cupping, massage therapy, spinal manipulation, even leeches. His first job was in a homeopathic hospital where a colleague chose remedies by dowsing with a pendulum. (more…)

Posted in: Book & movie reviews, Clinical Trials, Critical Thinking

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Screening for disease in people without symptoms: The reality

One of the most contentious questions that come up in science-based medicine that we discuss on this blog is the issue of screening asymptomatic individuals for disease. The most common conditions screened for that we, at least, have discussed on this blog are cancers (e.g., mammography for breast cancer, prostate-specific antigen screening for prostate cancer, ultrasound screening for thyroid cancer), but screening goes beyond just cancer. In cancer, screening is a particularly-contentious issue. For example, by simply questioning whether mammography saves as many lives lost to breast cancer as advocates claim, one can find oneself coming under fire from some very powerful advocates of screening who view any questioning of mammography as an attempt to deny “life-saving” screening to women. That’s why I was very interested when I saw a blog post on The Gupta Guide that pointed me to a new systematic review by John Ioannidis and colleagues examining the value of screening as a general phenomenon, entitled “Does screening for disease save lives in asymptomatic adults? Systematic review of meta-analyses and randomized trials.”

Before I get into the study, let’s first review some of the key concepts behind screening asymptomatic individuals for disease. (If you’re familiar with these concepts, you can skip to the next section.) The act of screening for disease is based on a concept that makes intuitive sense to most people, including physicians, but might not be correct for many diseases. That concept is that early intervention is more likely to successfully prevent complications and death than later intervention. This concept is particularly strong in cancer, for obvious reasons. Compare, for example, a stage I breast cancer (less than 2 cm in diameter, no involvement of the lymph nodes under the arm, known as axillary lymph nodes) with a stage III cancer (e.g., a tumor measuring greater than 5 cm and/or having lots of axillary lymph nodes involved). Five year survival is much higher for treated stage I than for treated stage III, and, depending on the molecular characteristics, the stage I cancer might not even require chemotherapy and can be treated with breast conserving surgery (“lumpectomy” or partial mastectomy) far more frequently than the stage III cancer. So it seems intuitively true that it would be better to catch a breast cancer when it’s stage I rather than when it’s stage III.

Posted in: Cancer, Clinical Trials, Epidemiology, Public Health

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Is the Ebola Crisis a Reason to Skip RCTs?

Ebola virus


In a recent “Perspective” article in The New England Journal of Medicine, three physicians (Drs. Cox, Borio, and Temple) make a strong case for not letting the rush to save Ebola patients tempt us to deviate from good science and skip the randomized controlled trial (RCT). Their arguments cut to the essence of the scientific approach to medicine, and they deserve careful consideration.

Ebola is uniquely scary

Ebola is the kind of threat that really gets our attention. The virus was first identified in 1976, and prior to 2013 there were several small outbreaks in Africa with death rates as high as 90%. This time the death rates are lower, but the numbers are much greater. It has spread to several African countries, and a few cases have even reached the US and Europe due to infected travelers and health care workers. We face a risk that Ebola may become endemic, smoldering along as a constant presence in Africa.

There is no known effective treatment. Fear of Ebola has sparked bizarre conspiracy theories and claims of “natural” cures and prevention kits from homeopaths, alternative medicine advocates like Mercola, and purveyors of remedies like colloidal silver and essential oils. These have been covered on SBM here, here, and here. (more…)

Posted in: Clinical Trials, Science and Medicine

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Acupuncture for Withdrawal Symptoms in Critically Ill Infants


Like acupuncture, Weebles wobble, but they don’t fall down.

The practice of medicine, particularly our pharmaceutical and surgical interventions, involves a constant struggle between risk and benefit. If the physiology or anatomy of the human body is altered, even with the best of intentions, there is always a potential downside. There are certainly instances where the risk to benefit ratio is extremely favorable or unfavorable and the right recommendation is obvious, and unfortunately there are times when it isn’t entirely obvious what the next step should be. But there has been a trend of steady progress in regards to improved safety and efficacy over the past several decades.

The treatment of pain has of late been one of those areas where the picture is becoming a bit less cloudy. We are learning more and more about the potential negative outcomes related to the long term use of opioid medications, such as physical dependence, addiction and even chronic pain. The way that these drugs have been prescribed in many patients has caused more harm than expected, and in some instances more hurt than help. Doctors generally strive to alleviate pain and suffering but, once again, good intentions don’t decrease risk.

In the neonatal and young infant population, the management of pain has had a rocky history. I’ve written about pediatric pain in the past, in particular the potential difficulties in managing acute pain. I won’t go into detail (read my prior post), but we have truly come a long way since the days of performing major surgery on newborns without any analgesia at all. There are areas where we need to do better, however. Children are still less likely than adults to be adequately treated for pain.

But things have improved. And as more children receive appropriate management for pain, the side effects of that management must increasingly be dealt with by healthcare professionals, the patients and their families. One of the issues that is typically observed and managed in neonatal and pediatric intensive care units is physical dependence and the subsequent occurrence of withdrawal symptoms.

Posted in: Clinical Trials

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Stem cells versus Gordie Howe’s stroke, part 2


Another Christmas has come and gone, surprisingly fast, as always. I had thought that it might make a good “last of 2014″ post—well, last of 2014 for me, anyway; Harriet and Steve, at least, will be posting before 2014 ends—to do an end of year list of the best and worst of the year. Unfortunately, there remains a pressing issue that doesn’t permit that, some unfinished business, if you will. I’m referring to a story I commented on last week, specifically the credulously-reported story of how 86-year-old hockey legend Gordie Howe is doing a lot better after having undergone an experimental stem cell therapy for his recent stroke. As you might recall at the time, I saw a lot of holes in the story. It turns out that over the last week there have been developments that allow me to fill in some of those holes. Unfortunately, other holes still remain.

First, a brief recap is in order (You can click here for a more detailed timeline). Gordie Howe suffered a massive stroke on October 26, leaving him hemiplegic and with serious speech impairment. Since then, judging from various media reports, he has been slowly improving, although not without significant setbacks. We also know that Howe suffers from significant dementia. Out of the blue, a press release issued on December 19 by the Howe family announced that on December 8 and 9, Gordie Howe “underwent a two-day, non-surgical treatment at Novastem’s medical facility. The treatment included neural stem cells injected into the spinal canal on Day 1 and mesenchymal stem cells by intravenous infusion on Day 2.” His response was described as “truly miraculous,” although, as I pointed out in my post, it’s not clear exactly what “miraculous” meant, given conflicting contemporaneous news accounts before the Howe family press release, particularly his hospitalization from December 1 to 3 for a suspected stroke that turned out to be dehydration.

I noted a number of problems with the story, the first of which is that Howe was clearly not eligible for the clinical trial offered by Stemedica, a company in San Diego that manufactured the stem cells used. Another glaring issue was my inability to locate any description of an actual clinical trial for stroke offered by Novastem. I could find no such trial listed in, and you, our intrepid readers, searched the registry maintained by the Mexican Federal Commission for the Protection Against Sanitary Risk (COFEPRIS) and were not able to find any registered clinical trials for stroke being carried out by Clínica Santa Clarita, the clinic Novastem operates. What you, our intrepid readers, did find were trials of stem cells for:

I did the search again over the weekend, and there were no further trials that I could find.

Posted in: Clinical Trials, Medical Ethics, Science and the Media

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Stem cells versus Gordie Howe’s stroke


Note: There is now a major update to this story published here, which explains a lot of the questions remaining in this blog post.

Seven years ago I returned to Michigan, where I was born and spent the first quarter century of my life, after an absence of more than 20 years. In the interim, I had done my surgical residency and earned my PhD in Cleveland, a surgical oncology fellowship in Chicago, and worked in New Jersey at my first academic job for eight and a half years. Then I was lured back with a job in Detroit. One of the odd things about this return after such a long absence was the culture shock, how much I had forgotten about the Detroit area. One of those things that I had forgotten is just how crazy about hockey Michigan, in particular Detroit (meaning the Detroit metropolitan area), is. Detroiters love their Red Wings—love them. Hockey is ingrained in the suburban culture from a very young age, so much so that many Canadians would feel right at home here. Memories of trying and failing to be halfway decent at street hockey and of not being anywhere good enough a skater even to try real hockey as a teen came flooding back to me. (It didn’t help that back then I was approaching six feet tall and weighed only 135 lbs.; “beanpole” didn’t even begin to describe me back then.) In fact, the “cultural center” of the town where I live consists of—I kid you not—a hockey rink and some classrooms that are used for various community functions. No, really, it’s named the city’s Cultural Center.

So it should be no surprise, given how much Detroiters love hockey in general and their Red Wings in particular that it was big news here in late October when Red Wing legend Gordie Howe at age 86 suffered a debilitating stroke that paralyzed the right side of his body, a condition known as hemiplegia. Understandably, there was an outpouring of good wishes for recovery, coupled with retrospectives of Howe’s stellar hockey career. Indeed, I remember that Howe’s condition sounded bad enough from the tenor of the news reports at the time that it seemed likely that he would not survive. But survive he did, and is apparently recovering slowly, with occasional setbacks, such as a recent hospitalization in early December for a suspected “mini-stroke” that turned out to be dehydration and several much smaller strokes before that. The most recent press report I saw before the announcements I’m going to discuss described Howe as on the upswing again.

Then, on Friday, I saw headlines all over the place that were basically similar to this Detroit Free Press headline, “Gordie Howe underwent stem cell clinical trial in Mexico.” The story consisted largely of a press release from Howe’s family that read:

Posted in: Clinical Trials, Medical Ethics, Pharmaceuticals, Science and the Media

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Study of “Acupressure” for Constipation

constipationA recent study in the Journal of General Internal Medicine evaluated a treatment for constipation. It tested whether training patients to massage the perineum (the area between the vagina or scrotum and the anus) would improve their reported bowel function and quality of life at 4 weeks after training. They found that it did. It’s a simple, innocuous treatment that may be worth trying, but why, oh why, did they have to call it “acupressure”? That irritated me. Should it have? Why should it matter? Isn’t a rose by any other name still a rose? Is this a meaningless semantic quibble and hypersensitivity on my part, or am I right to see it as yet another example of quackademia’s attempts to infiltrate science-based medicine? I’ll explain my thinking and let you decide for yourself. (more…)

Posted in: Acupuncture, Clinical Trials, Traditional Chinese Medicine

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Selling “integrative oncology” as a monograph in JNCI


Sometimes, it’s hard not to get the feeling that my fellow bloggers at Science-Based Medicine and I are trying to hold back the tide in terms the infiltration of pseudoscience and quackery into conventional medicine, a term I like to refer to as quackademic medicine. In most cases, this infiltration occurs under the rubric of “complementary and alternative medicine” (CAM), which these days is increasingly referred to as “integrative medicine,” the better to banish any impression of inferior status implied by the name “CAM” and replace it with the implication of a happy, harmonious “integration” of the “best of both worlds.” (As I like to point out, analogies to another “best of both worlds” are hard to resist.) Of course, as my good buddy Mark Crislip has put it, the passionate protestations of CAM advocates otherwise notwithstanding, integrating cow pie with apple pie doesn’t make the cow pie better. Rather, it makes the apple pie worse.

In any case, over the last three months, Steve Novella and I published a solid commentary in Trends in Molecular Medicine decrying the testing in randomized clinical trials of, in essence, magic, while I managed to score a commentary in Nature Reviews Cancer criticizing “integrative oncology.” Pretty good, right? What do I see this month in the Journal of the National Cancer Institute (or JNCI, as we like to call it)? An entire monograph devoted to a the topic, “The Role of Integrative Oncology for Cancer Survivorship”, touting integrative oncology, of course. And where did I find out about this monograph? I found out about it from Josephine Briggs, the director of the National Center for Complementary and Alternative Medicine (NCCAM) herself, on the NCCAM blog in a post entitled “The Evidence Base for Integrative Approaches to Cancer Care“, in which she touts her perspective piece in the JNCI issue entitled “Building the Evidence Base for Integrative Approaches to Care of Cancer Survivors.” In an introductory article, Jun J. Mao and Lorenzo Cohen of the Department of Family Medicine and Community Health, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania and the University of Texas M.D. Anderson Cancer Center, respectively, line up this monograph thusly:

Posted in: Cancer, Clinical Trials, Medical Academia

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Eminent Harvard psychologist, mother of positive psychology, New Age quack?

Eminent Harvard psychologist, mother of positive psychology, New Age quack?

Be less curious about people and more curious about ideas.
– Marie Curie’s advice to journalists

langer cbs this

Harvard psychologist Ellen Langer was on CBS This Morning News explaining plans for a psychosocial intervention study with women with Stage IV metastatic breast cancer. The project would attempt to shrink women’s tumors by shifting their mental perspective back to before they were diagnosed.
Seeing her on TV unsettled me because I had just supplied a journalist with quotes for his article in the New York Times about Langer. I hadn’t been following her recently. Instead I focused on her now-famous study from the 70s. Langer had claimed that giving nursing home residents a plant for which they were responsible cut their mortality by half (the nursing home residents, not the plant), compared to residents whose plants were attended by staff. The paper continues to get uncritical coverage in the media and in introductory psychology texts.

I looked up the Timesarticle after seeing CBS This Morning News, and it accurately quoted me:

Posted in: Cancer, Clinical Trials, Medical Ethics

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