Articles

Archive for Science and Medicine

How not to consult your biostatistician before doing an experiment

A friend of mine at work sent this video to me in great amusement.

I just hope he wasn’t making a comment on my behavior when it comes to dealing with our biostatisticians. I have, of course, seen investigators approach biostatistians this late in the game. Not that I’ve ever flirted with this sort of behavior, of course. At least the researcher in the video above actually consulted the biostatistician before doing the experiment, rather than after doing an experiment with inadequate statistical power to answer the question asked. On the other hand, I guess it doesn’t matter if the researcher doesn’t listen, does it?

Posted in: Humor, Science and Medicine

Leave a Comment (8) →

Evidence-Based Medicine, Human Studies Ethics, and the ‘Gonzalez Regimen’: a Disappointing Editorial in the Journal of Clinical Oncology Part 2

NB: If you haven’t yet read Part 1 of this blog, please do so now; Part 2 will not summarize it.

At the end of Part 1, I wrote:

We do not need formal statistics or a new, randomized trial with a larger sample size to justify dismissing the Gonzalez regimen.

In his editorial for the JCO, Mark Levine made a different argument:

Can it be concluded that [the] study proves that enzyme therapy is markedly inferior? On the basis of the study design, my answer is no. It is not possible to make a silk purse out of a sow’s ear.

That conclusion may be correct in the EBM sense, but it misses the crucial point of why the trial was (ostensibly) done: to determine, once and for all, whether there was anything to the near-miraculous claims that proponents had made for a highly implausible “detoxification” regimen for cancer of the pancreas. Gonzalez himself had admitted at the trial’s inception that nothing short of an outcome matching the hype would do:

DR. GONZALEZ: It’s set up as a survival study. We’re looking at survival.

SPEAKER: Do you have an idea of what you’re looking for?

DR. GONZALEZ: Well, Jeff [Jeffrey White, the director of the Office of Cancer Complementary and Alternative Medicine at the NCI—KA] and I were just talking a couple weeks ago. You know, to get any kind of data that would be beyond criticism is—-always be criticism, but at least three times.

You would want in the successful group to be three times — the median to be three times out from the lesser successful groups.

So, for example, if the average survival with chemo, which we suspect will be 5 months, you would want my therapy to be at least — the median survival to be at least 15, 16, 17 months, as it was in the pilot study.

We’re looking for a median survival three times out from the chemo group to be significant.

Recall that the median survival in the Gonzalez arm eventually turned out to be 4.3 months.

(more…)

Posted in: Cancer, Clinical Trials, Health Fraud, Medical Academia, Medical Ethics, Politics and Regulation, Science and Medicine

Leave a Comment (30) →

Evidence-Based Medicine, Human Studies Ethics, and the ‘Gonzalez Regimen’: a Disappointing Editorial in the Journal of Clinical Oncology Part 1

Background: the distinction between EBM and SBM

An important theme on the Science-Based Medicine blog, and the very reason for its name, has been its emphasis on examining all the evidence—not merely the results of clinical trials—for various claims, particularly for those that are implausible. We’ve discussed the distinction between Science-Based Medicine (SBM) and the more limited Evidence-Based Medicine (EBM) several times, for example here (I began my own discussion here and added a bit of formality here, here, and here). Let me summarize by quoting John Ioannidis:

…the probability that a research finding is indeed true depends on the prior probability of it being true (before doing the study), the statistical power of the study, and the level of statistical significance.

EBM, in a nutshell, ignores prior probability† (unless there is no other available evidence) and falls for the “p-value fallacy”; SBM does not. Please don’t bicker about this if you haven’t read the links above and some of their own references, particularly the EBM Levels of Evidence scheme and two articles by Steven Goodman (here and here). Also, note that it is not necessary to agree with Ioannidis that “most published research findings are false” to agree with his assertion, quoted above, about what determines the probability that a research finding is true.

The distinction between SBM and EBM has important implications for medical practice ethics, research ethics, human subject protections, allocation of scarce resources, epistemology in health care, public perceptions of medical knowledge and of the health professions, and more. EBM, as practiced in the 20 years of its formal existence, is poorly equipped to evaluate implausible claims because it fails to acknowledge that even if scientific plausibility is not sufficient to establish the validity of a new treatment, it is necessary for doing so.

Thus, in their recent foray into applying the tools of EBM to implausible health claims, government and academic investigators have made at least two, serious mistakes: first, they have subjected unwary subjects to dangerous but unnecessary trials in a quest for “evidence,” failing to realize that definitive evidence already exists; second, they have been largely incapable of pronouncing ineffective methods ineffective. At best, even after conducting predictably disconfirming trials of vanishingly unlikely claims, they have declared such methods merely “unproven,” almost always urging “further research.” That may be the proper EBM response, but it is a far cry from the reality. As I opined a couple of years ago, the founders of the EBM movement apparently “never saw ‘CAM’ coming.”

(more…)

Posted in: Cancer, Clinical Trials, Medical Academia, Medical Ethics, Politics and Regulation, Science and Medicine

Leave a Comment (59) →

Chronic Fatigue Syndrome: Lots of Speculation

Humans love to find patterns in the world. Sometimes patterns exist, sometimes they are imaginary. Sometimes you can see a pattern that may be interesting and ignore its significance. As a resident I used to say that anyone who smokes three packs of cigarettes a day has to be schizophrenic, it was meant more as a joke, when, in fact, it was later discovered that tobacco helps ameliorate the symptoms of schizophrenia. I need to pay more attention.

Part of my job is to look for patterns as a key to the patients diagnosis. Diseases and pathogens tend to (more or less) cause reproducible signs and symptoms and looking for that pattern is often the most helpful clue towards finding the diagnosis. Of course things are never as easy as one would like, as you have to consider whether you are seeing common manifestations of a common disease, uncommon manifestations of a common disease, common manifestations of a uncommon disease and, the hardest, uncommon manifestations of an uncommon disease. When I have a complex or uncertain cause, I explicitly run through that, and other, litanies so I do not miss a unusual diagnosis.

Chronic Fatigue Syndrome (CFS) has, at least to my way of thinking, two patterns. I see the occasional CFS patient in clinic and, I hope, pay attention to their disease patterns. I keep in mind I may be seeing a pattern that does not exist, but looking for disease patterns is what doctors are trained to do.

(more…)

Posted in: Basic Science, Science and Medicine

Leave a Comment (27) →

Your disease, your fault

Earlier this week, my colleague Dr. Gorski explored a common theme in alternative medicine: the idea that all disease is preventable.  This implies that all disease has a discrete cause and that individual behavior can mitigate this cause.

If biology worked this way, my job as an internist would be very different.   Many people would love to believe that life is this predictable, and that they have that much control over their health, but they don’t.  Most disease represents the interaction of environment and genetics, and you can’t change your genes (with a few exceptions, of course).

It’s natural to want to be able to exert an impossible level of control over your health, but when unscrupulous charlatans (redundant redundancy alert!) play on these beliefs and fears, they can cause, rather than prevent problems.

(more…)

Posted in: Science and Medicine

Leave a Comment (62) →

Ghostwriting As Marketing Tool

An article in the latest issue of PLOS Medicine, The Haunting of Medical Journals: How Ghostwriting Sold “HRT”, details the use of ghostwriting as a marketing tool for pharmaceutical companies. It is a chilling discussion of how at least one pharmaceutical company, Wyeth, used the peer-reviewed literature as a method of distributing marketing messages to physicians.

The author, Adriane J. Fugh-Berman, details a practice that cuts at the heart of science-based medicine – the exploitation and distortion of the literature. The medical profession needs to jealously guard the legitimacy and purity of the peer-review process and the medical scientific literature. I am never one to gratuitously bash “Big Pharma” – this is often used as a method of casually dismissing inconvenient scientific evidence. But at the same time, pharmaceutical companies are in the business of making money. While they are a carefully regulated industry, some in the industry seek ways to skirt around regulations that limit their ability to market their products.

While most physicians consider themselves savvy with respect to pharmaceutical marketing, the story told by Fugh-Berman is one of profound naivete. I guess it should not be a surprise that some academics were bamboozled by expert salespersons who spent a lot of time and effort, apparently, figuring out ways to deceive and manipulate them. But now that the story is out, naivete is no longer an excuse. Here is what happened:

(more…)

Posted in: Medical Ethics, Pharmaceuticals, Politics and Regulation, Science and Medicine

Leave a Comment (32) →

WHO Partnering with Traditional Healers in Africa

There is an AIDS epidemic in Africa, and efforts to fight it are hampered by the endemic social problems of that continent. Chief among them are the lack of sufficient modern health resources, the spread of destructive rumors and myths about HIV/AIDS, and even the persistence of HIV denial in Africa (although this last factor is better than in the past).

The World Health Organization (WHO) and the International HIV/AIDS Alliance are teaming up with the Traditional Health Practitioners Association of Zambia (THPAZ) to address the first problem – the lack of health services. Most Zambians use traditional healers for primary health care. The WHO has therefore decided to utilize traditional healers in the fight against AIDS. There are interesting pros and cons to this policy, but it must first be recognized that there is no ideal solution to the problem. The resources to provide optimal modern health care to treat and prevent HIV/AIDS (which would need to include a massive education program) in Zambia and the rest of Africa simply do not exist. One might argue that the world should provide those resources, but let’s put that issue aside and focus on what to do in the meantime.

The arguments given in favor of this WHO strategy are:

Traditional healers far outnumber biomedical workers in the rural areas.

They are consulted, not only because they are closer and more affordable than their Western-trained counterparts, but also because they are embedded, extensively and firmly, within Ugandan culture.

Traditional healers are highly respected and widely consulted by communities.

(more…)

Posted in: Public Health, Science and Medicine

Leave a Comment (23) →

Reflexology. Insert Nancy Sinatra Reference Here.

Note:  I think the following post is perfect in terms of spelling and grammar.  It isn’t.  I am starting to think I have a language processing problem given the typo’s that seem to slip in to each post.  Be that as it may, there is a subset of readers who get their underoo’s in a twist at missing articles and apostrophes.  If you are one of those readers, come back in a day.  This post will be proofread and corrected, at which time this note will be missing and you can read the text without the pain of my poor grammar  skills.

In the last post on acupuncture, I noted that the University of Maryland offered, among other supplements, complementary and alternative medicine (SCAMs), reflexology.  I was uncertain as to the particulars of this SCAM, and this post is a result of those investigations. (more…)

Posted in: Energy Medicine, Science and Medicine

Leave a Comment (0) →

Why bother?

It can be rather frustrating to refute the same old canards about alternative medicine.  There’s always been argument as to whether this is even useful.  Critics (some verging on “concern troll-ism”) argue that skeptics are convincing no one, others that we are too “dickish”. The first view is overly pessimistic (re: our impact), the second overly optimistic (re: the benign nature of our critics).   The truth always bears repeating, even at the risk of becoming the old guy at the end of the bar who always starts his stories off with, “Did I ever tell you…?”  The answer is always “yes” but if the story is good, and well-told, it may stand up to re-telling.

We tell many versions of the same story over and over, not just to entertain each other, but to refine our thinking, to convince those who can be convinced, and to point out the weakness in thinking apparent in others.  We do this not to be “dicks” but because repeated assaults on reason require repeated defense.   Scientific medicine gives us a powerful tool for analyzing new ideas and old ones dressed up in new clothes.  It allows us to find ourselves to be wrong in particular facts, if not in our overall approach.
(more…)

Posted in: Acupuncture, Science and Medicine, Science and the Media

Leave a Comment (15) →

Does peer review need fixing?

One of the most important aspects of science is the publication of scientific results in peer-reviewed journals. This publication serves several purposes, the most important of which is to communicated experimental results to other scientists, allowing other scientists to replicate, build on, and in many cases find errors in the results. In the ideal situation, this communication results in the steady progress of science, as dubious results are discovered and sound results replicated and built upon. Of course, scientists being human and all, the actual process is far messier than that. In fact, it’s incredibly messy. Contrary to popular misconceptions about science, it doesn’t progress steadily and inevitably. Rather, it progresses in fits and starts, and most new scientific discoveries go through a varying period of uncertainty, with competing labs reporting conflicting results. To achieve consensus about a new theory can take relatively little time (for example, the less than a decade that it took for Marshall and Warren’s hypothesis that peptic ulcer disease is largely caused by H. pylori or the relatively rapid acceptance of Einstein’s Theory of Relativity) to much longer periods of time.

One of the pillars of science has traditionally been the peer review system. In this system, scientists submit their results to journals for publication in the form of manuscripts. Editors send these manuscripts out to other scientists to review them and decide if the science is sound, if the methods appropriate, and if the conclusions are justified by the data presented. This step of the process is very important, because if editors don’t choose reviewers with the appropriate expertise, then serious errors in review may occur. Also, if editors choose reviewers with biases so strong that they can’t be fair, then science that challenges such reviewers’ biases may never see print in their journals. The same thing can occur to grant applications. In the NIH, for instance, the scientists running study sections must be even more careful in choosing scientists to be on their study sections and review grant applications, not to mention picking which scientists review which grants. Biases in reviewing papers are one thing; biases in reviewing grant applications can result in the denial of funding to worthy projects in favor of projects less worthy that happen to correspond to the biases of the reviewers.

I’ve discussed peer review from time to time, although perhaps not as often as I should. My view tends to be that, to paraphrase Winston Churchill’s invocation of a famous quote about democracy, peer review is the worst way to weed out bad science and promote good science, except for all the others that have been tried. One thing’s for sure, if there’s a sine qua non of an anti-science crank, it’s that he will attack peer review relentlessly, as HIV/AIDS denialist Dean Esmay did. Indeed, in the case of Medical Hypotheses, the lack of peer review let the cranks run free to the point where even Elsevier couldn’t ignore it any more. One thing’s for sure. Peer review may have a lot of defects and blindnesses, but lack of peer review is even worse. It’s no wonder why cranks of all stripes loved Medical Hypotheses.
(more…)

Posted in: Medical Academia, Science and Medicine

Leave a Comment (42) →
Page 42 of 87 «...1020304041424344...»