This is the second installment analysis of a three (and now 4) part series of articles on effects of homeopathy on childhood diarrhea. This second installment elaborates on our findings on data from the second clinical trial in Nicaragua. (1)
I should first explain the title. In order for homeopathy to operate as a base or operating system for medicine “for the 21st century,” the entire system of measurement and of course all physical laws would have to be changed. In analogous political terms, it would be similar to – but more massive a change than – changing a nation from a democracy to a completely different system such as a theocracy with completely different laws and behavior expectations. So…well, it was the best I could think up at the time.
Last time I recounted how the Jacobs ll trial setup was incoherent and unable to produce results that could prove efficacy – unless the differences between treatment and controls were quite large, greater than just barely significant. Most patients were treated differently from others, with multiple preparations (that were in reality the same: pill filler) at differing times during the illness, with each preparation selected according to symptoms that likely varied by the hour, and influenced by memory, well known to be faulty in medical studies.
In fact, given the lack of homogeneity in the trial diagnoses and treatments, outcomes should not have made sense at all. Now I must admit that the thought did not occur to us at the time we undertook the review, nor during the review. If it had, our job would have been easier and the paper shorter.
This week I thought you all might enjoy a reprint of a humorous post from Better Health. Dr. Rob Lamberts explores the curious obsession that some Hollywood celebrities have with “toxins.” Sometimes laughter is the best medicine:
Somehow the medical community has missed a very important news Item. In her website goop.com (dang, I was going to go for that domain), movie star Gwyneth Paltrow weighed in on a very frightening medical subject.
“A couple of years ago, I was asked to give a quote for a book concerning environmental toxins and their effects on our children.
“While I was reading up on the subject, I was seized with fear about what the research said. Foetuses, infants and toddlers are basically unable to metabolise toxins the way that adults are and we are constantly filling our environments with chemicals that may or may not be safe.
“The research is troubling; the incidence of diseases in children such as asthma, cancer and autism have shot up exponentially and many children we all know and love have been diagnosed with developmental issues like ADHD [Attention Deficit Hyperactivity Disorder].”
Apparently, she went on to point the finger at shampoo as a potential major problem in our society and raised a possible link between shampoo and childhood cancers. Now, I am not sure how one can use shampoo on the head of a foetus (or a fetus, for that matter), but we have to tip our hat to celebrities for bringing such associations to the forefront.
It is unfortunately a common human reaction to respond to criticism by attacking those leveling the criticism, rather than addressing the points being made. This is especially true if the criticism is legitimate and one cannot reasonably counter it.
Substantive criticism is also a central part of the scientific endeavor, and so the culture of science has developed a tolerance for harsh criticism and a general understanding that the only proper response is with logic and evidence. Examples of exceptions are legion, human frailty being what it is, but you cannot live in the world of science for long without learning the rules of the game. Peers are expected to pull no punches when criticizing the errors or countering the arguments of their colleagues. Everyone is expected to be their own harshest critic (criticize your own data before someone has a chance to). And when criticized yourself, acknowledge what is legitimate and make appropriate corrections, but feel free to defend yourself against weak criticisms by pointing out additional data, interpretations, or errors in the arguments of your critics.
This meat grinder approach to scientific discourse works. Slowly, bad ideas and claims are beaten down, and only good ideas have the stamina to persist.
But here at science-based medicine we engage not only with the scientific community, but also with the public, and with those on the fringes of science. This means we often engage with those who do not play by the rules of science. A recent example is that of J.B. Handley from Age of Autism. David Gorski and I (and later Mark Crislip) wrote blog entries criticizing their 14 studies website with a detailed analysis. Handley responded with a full frontal personal assault sprinkled with irrelevant accusations. He ignored the vast majority of our actual criticisms, and those few he took on he completely botched.
I read this Reuters Health article on MedlinePlus, and then I read the study the article referred to (The impact of acupuncture on in vitro fertilization) and now my head hurts. The study found that acupuncture was not effective in increasing the pregnancy rate (PR) during in vitro fertilization (IVF). As quoted on MedlinePlus, the lead author, Alice Domar, seems to blame her patients (the presumably poor quality of their embryos) rather than acupuncture for the lack of success, and then she recommends using acupuncture even if it doesn’t work. That was bad enough, but “poor quality embryos” is a hypothesis that was actually tested and rejected in the study itself. Has Domar forgotten?
The headline of the MedlinePlus article says “acupuncture doesn’t boost IVF success for all” – suggesting that it boosts success for some? Then the first sentence says the study suggested that acupuncture doesn’t work, period. But wait…
The lead researcher says acupuncture may not have worked in her study because, unlike past research, her investigation wasn’t limited to women who had good quality embryos available for transfer. “I’m wondering if my sample was just not a good sample, in that most of the patients in my study were probably not the best-prognosis patients,”
Domar and her team say the most likely explanation for the lack of an acupuncture effect in their study was the fact that they included many women who didn’t have good quality embryos available for transfer. While acupuncture may help a woman become pregnant after the transfer of a healthy embryo, the researcher noted in an interview, it can’t repair an embryo with chromosomal defects or other abnormalities.
Hold the boat!! In the Discussion section of the paper itself, Domar et al point out that previous research has included mostly patients with good quality embryos. They ask if perhaps acupuncture only works for good quality embryos? They test that hypothesis by separately analyzing the subjects in this study who had good quality embryos. There was no increase in PR with acupuncture in this sub-group; the results were the same as for the entire sample. (more…)
Arguably the most difficult aspect of science-based medicine is where the rubber hits the road, so to speak. That’s where scientists and physicians take the results of preclinical studies performed in vitro in biochemical assays and cell culture models and in vivo in animal models to humans. There are numerous reasons for this, not the least of which that preclinical models, contrary to what animal rights activists would like you to believe, do not predict human responses to new therapeutic agents as much as we would like. However, the single biggest reason that we cannot answer questions in human studies as easily as we can in cell culture and animal studies is ethics. Of course, answering questions using cell culture and animal studies is not “easy,” either, but performing studies using human beings as subjects is an order of magnitude (at least) more difficult because the potential to cause harm exists, and if harm is caused by the experimental treatment under study, that harm will be done to human beings, rather than cells in a dish or mice bred for research.
The “gold standard” type of study that we do to test the efficacy of a new drug is known as the randomized, placebo-controlled, double-blinded study, often abbreviated RCT. Indeed, this remains the gold standard and is accorded the highest level of “power” in the framework of evidence-based medicine. Of course, as we have argued time and time again, using the RCT to test therapies that are incredibly implausible on a strictly scientific basis (homeopathy or reiki, for instance) inevitably leads to numerous “false positives” in which the therapy appears to produce results statistically significantly better than the control. John Ioannidis has done numerous clever analyses that demonstrate how easily clinical research is led astray if it is not grounded in scientific plausibility. Indeed, the probability of false positive studies increases, the more improbable the modality. It is for these very reasons that we have proposed the concept of science-based medicine, which takes into account estimates of prior probability based on preclinical studies and basic scientific principles, rather than evidence-based medicine, which does not. Indeed, Wally Sampson has even proposed a “plausibility scale” for rating RCTs, and Steve Novella has pointed out how difficult it can be to interpret the medical literature.
First off, I have deliberately not read the entries on Fourteen Studies by fellow bloggers on SBM. I wanted to go through the information on the site myself. So if some of the information is repetitive, sorry.
Second, in the interest of openness and transparency, I will state my conflicts of interest up front: none. I have not talked to a drug rep in at least 20 years. Outside of a trip to San Francisco as a fellow, paid for by the company who was funding a drug study my boss was participating in, I have accepted no gifts or money of any kind from big (or little) pharma since I was a medical student. Nothing. I don’t even eat the pizza at conferences (1).
Third, I am a hospital based adult Infectious Disease doctor. I make zero money from vaccines. In fact, I only make money if people get sick with infections. For my bottom line, giving vaccines to prevent disease is counter productive to my bottom line.
Why 14 studies?
I am writing this because a colleague of mine has been attacked, specifically, our fearless leader Steve Novella. J.B. Handley, Founder of “Jenny McCarthy and Jim Carrey’s Autism Organization – Generation Rescue” (whose usurpation by Jenny and Jim was apparently done in an opportunistic fashion but has had a consequence that must be galling to J.B., namely that some interviewers apparently think that Jenny McCarthy and Jim Carrey, not J.B. and his wife, are the true founders of Generation Rescue), did not like something that Steve wrote and in his characteristic fashion, has responded with a vicious ad hominem attack. Normally I wouldn’t feel obligated to put my two cents in, as Steve is more than capable of taking care of himself in a scientific argument and quite able to refute anything J.B. can throw at him. Moreover, whenever J.B. Handley attacks someone in a fashion this nasty, it is an excellent indication that the person he is attacking has scored some serious points against him. Indeed, I have twice been on the receiving end of J.B.’s tirades on the Generation Propaganda blog Age of Autism. On one occasion, he referred to me as the “worldwide wanker of woo,” and on another occasion seemed to think that I criticized Generation Rescue so harshly because I “don’t like full page ads,” rather than because I hate pseudoscience and anti-vaccine nonsense. When criticism really hits a nerve with J.B. Handley, he lashes out in a characteristic fashion. Clearly Steve’s reasoned, level-headed criticism of the latest Generation Rescue anti-vaccine propaganda initiative did just that.
In this case, however, I feel some explanation is in order because I feel a bit responsible for having brought J.B.’s wrath down upon Steve. First, a little history (albeit recent history) is in order. As I described in detail last week and the week before, Generation Rescue, with Jenny McCarthy and Jim Carrey at the fore, sometimes with J.B. himself, has mounted an impressive anti-vaccine propaganda effort. It started with a media tour promoting her most recent paean to anti-vaccine pseudoscience and autism quackery written with “co-author” Dr. Jerry Kartzinel. The book is entitled Healing and Preventing Autism: A Complete Guide, and three weeks ago Jenny McCarthy and her boyfriend Jim Carrey showed up on Larry King Live to tout a truly incompetent and intellectually dishonest “study” that purported to find that U.S. children are the “most highly vaccinated children in the world” and that that’s correlated with our higher autism rates. I would have none of it. Next, Generation Rescue introduced its equally intellectually dishonest “Fourteen Studies” website, which launched dubious attacks from pseudoexperts on fourteen of the major studies that failed to find a correlation between vaccines and autism or thimerosal-containing vaccines and autism. I wrote a lengthy post for SBM describing the utter intellectual and scientific bankruptcy of the entire enterprise.
One of the more frustrating things about practitioners who promote unsafe and scientifically discredited medical practices is their tendency to change their message for different audiences. One day they’ll tell you that they espouse only evidence-based practices and the next they’ll be promoting snake oil. This double talk is hard to combat, since to disprove them one would essentially have to provide a video of their contradictory remarks.
One day I participated in a series of business meetings with a CAM practitioner in attendance (he was an MD who graduated from UCSF). During one meeting he boldly proclaimed his support of scientifically rigorous research, and praised the Cochrane Collaborative’s efforts to provide systematic reviews of the evidence (or lack thereof) for various practices.
Several hours later we were sitting together in another meeting in which I objected to the publication of a consumer article that would assist parents of children with autism in finding a DAN! practitioner who could provide chelation therapy to their children. I explained that there was no evidence for the efficacy of such treatments, and plenty of evidence for their harm (including the death of at least one child that I’d read about in the news). I suggested that an article describing these dangers might be in order, but that an article encouraging chelation use for autism was simply unethical and I would not allow it to be published.
Instead of agreeing with me, the CAM MD suggested that I was being “narrow” and that I should allow consumers to “explore all their options.” I was stunned. This was the same person who had just said that he fully supported scientific inquiry. So I asked him how he could say that he supported evidence-based medicine, and then turn around and ignore evidence at will – even at the peril of human life.
His response dumbfounded me:
“I am just as comfortable practicing within an evidence-based framework as I am outside it.”
As many have pointed out, we are in the midst of a transformation in the way news is created, distributed, and monetized – all brought on by the internet. Access to information has dramatically increased, while the traditional news outlets are fading away. The new internet-based outlets that are cropping up are often hybrids that do not fit into any existing definition. Science-based medicine itself is such an outlet – it’s primarily a group professional blog, but we have editors and take submissions. We also plan to expand the type of resources available on SBM. We’re experimenting.
Others, like Plos ONE, are experimenting with open-access peer-reviewed journals. And there are online newspapers that are part blog, part news feed, part something else.
While we are in this phase of experimentation it is important to monitor quality control, as the old institutions lose their grip on the flow of information. Health information in particular, now the most common type of information on the internet, suffers from poor quality control, leading the average consumer with too much information of too low quality.
We criticize alternative medicine for not being evidence-based, and they criticize conventional medicine in turn, saying that much of what conventional medicine does is not based on evidence either. Sometimes that criticism is justified. I have run across a conventional practice that I suspect began because it sounded like a good idea, but that never was adequately tested and is not carefully thought out for individual patients.
I recently had a bone marrow aspiration. The written instructions said not to eat or drink for 6 hours before the procedure, to bring someone to drive me home, and to expect an IV. I suspected from these instructions that they were planning to use IV sedation, and I was right.
I questioned the need for sedation. I am prejudiced about bone marrow aspirations. I observed several and did one myself during my internship. When I had finished, the patient asked me when I was going to start. We did the procedure at the patient’s bedside in a multi-bed ward with no sedation, only local anesthesia. So my prejudice was that the procedure was no big deal and was not terribly painful.
I can imagine that some patients may be terrified by the idea of a needle going into their bone and may want to be sedated and not remember the experience. But I was not anxious about it, and I saw no need for the fentanyl and Versed they wanted to give me. I figured it would only prolong my time in the hospital, produce amnesia, expose me to a small risk of adverse effects, and leave me groggy; so I asked to opt out. They readily agreed – although they did keep asking me if I was really sure I didn’t want it. They would not have offered the option of no sedation if I had not known to ask. (more…)