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Archive for Clinical Trials

The Canadian National Breast Screening Study ignites a new round in the mammography wars

The last couple of weeks, I’ve made allusions to the “Bat Signal” (or, as I called it, the “Cancer Signal,” although that’s a horrible name and I need to think of a better one). Basically, when the Bat Cancer Signal goes up (hey, I like that one better, but do bats get cancer?), it means that a study or story has hit the press that demands my attention. It happened again just last week, when stories started hitting the press hot and heavy about a new study of mammography, stories with titles like Vast Study Casts Doubts on Value of Mammograms and Do Mammograms Save Lives? ‘Hardly,’ a New Study Finds, but I had a dilemma. The reason is that the stories about this new study hit the press largely last Tuesday and Wednesday, the study having apparently been released “in the wild” Monday night. People were e-mailing me and Tweeting at me the study and asking if I was going to blog it. Even Harriet Hall wanted to know if I was going to cover it. (And you know we all have a damned hard time denying such a request when Harriet makes it.) Even worse, the PR person at my cancer center was sending out frantic e-mails to breast cancer clinicians because the press had been calling her and wanted expert comment. Yikes!

What to do? What to do? My turn to blog here wasn’t for five more days, and, although I have in the past occasionally jumped my turn and posted on a day not my own, I hate to draw attention from one of our other fine bloggers unless it’s something really critical. Yet, in the blogosphere, stories like this have a short half-life. I could have written something up and posted it on my not-so-secret other blog (NSSOB, for you newbies), but I like to save studies like this to appear either first here or, at worst, concurrently with a crosspost at my NSSOB. (Guess what’s happening today?) So that’s what I ended up doing, and in a way I’m glad I did. The reason is that it gave me time to cogitate and wait for reactions. True, it’s at the risk of the study fading from the public consciousness, as it had already begun to do by Friday, but such is life.
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Posted in: Cancer, Clinical Trials, Diagnostic tests & procedures, Public Health

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The Pollyanna Phenomenon and Non-Inferiority: How Our Experience (and Research) Can Lead to Poor Treatment Choices

Pollyanna, a popular children’s book written in 1913 by Eleanor H. Porter, introduced the world to one of the most optimistic fictional characters ever created. She always saw the good in people and her approach to life frequently involved playing “The Glad Game”, where she attempted to find something to appreciate in every situation no matter how unfortunate. She was glad about receiving crutches rather than a doll one Christmas because it was great that she didn’t actually need them. She teaches this philosophy to those around her, even her cantankerous Aunt Polly, and the entire town is transformed into a veritable Mayberry, USA. Later, when she actually does require the use of crutches, her resolve is tested but she triumphantly finds a silver lining.

The Pollyanna principle, first described by Matlin and Stang in 1978 and also known as positivity bias, is a psychological tendency for people to place greater importance on, and assume better accuracy of, descriptive statements about them that are positive. This goes on behind the scenes while our conscious brain tends to dwell on what is perceived as negative stimuli. Though many folks do come across as pessimistic, we are subconsciously biased to accept praise and reject criticism. Anyone who isn’t clinically depressed is on some level more like Pollyanna than Eeyore.

This positivity bias also plays a large role in how we remember past events. As has been covered extensively in prior posts here on SBM, and on Dr. Novella’s excellent Neurologica blog, memory isn’t a replayed video or audio recording of prior events and our interpretations of them, but rather is a reconstruction that is prone to errors during processing and editing that accumulate over time. This leads to false memories that feel no less real than our recollection of what happened five minutes ago.

In this case, the Pollyanna principle results in positive information being more accurately processed and recalled than negative experiences. It also causes our memory of negative events to gradually become less negative as the years go by. I couldn’t have done that terribly during my first high school trumpet solo because I remember people telling me it was pretty good afterwards, right?

So what does this have to do with the practice of medicine? Biases that affect memory also impact how physicians and patients interact. I once assumed the overnight care of a child who had undergone a lumbar puncture performed by one of my female colleagues earlier that day. I ordered no tests and performed no procedures during my brief exposure to the family—yet over a year later when I admitted the same child for a completely different reason I was accused of being the terrible doctor who had unnecessarily subjected their baby to a spinal tap during the last hospitalization. Even after I showed them the documentation which proved that I had nothing to do with that (very appropriate) decision, and that I did not put a needle in their child’s spine, they refused to accept the evidence and had great difficulty trusting my diagnosis and recommendations.
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Posted in: Clinical Trials, Pharmaceuticals

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The return of the revenge of high dose vitamin C for cancer

Somehow, I’ve a feeling we’re not in Kansas anymore—except that we are, as you will soon see.

Because I’m the resident cancer specialist on this blog, it usually falls on me to discuss the various bits of science, pseudoscience, and quackery that come up around the vast collection of diseases known collectively as “cancer.” I don’t mind, any more than my esteemed colleague Dr. Crislip minds discussing infectious diseases and, of course, vaccines, the most effective tool there is to prevent said infectious diseases. In any case, there are certain things that can happen during a week leading up to my Monday posting slot on SBM that are the equivalent of the Bat Signal. Call them the Cancer Signal, if you will. One of these happened last week, thus displacing that post I’ve been meaning to write on a particular topic once again. At this rate, I might just have to find a way to write an extra bonus post. But not this week.

In any case, this week’s Cancer Signal consisted of a series of articles and news reports with titles like:

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Posted in: Basic Science, Cancer, Clinical Trials

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Treating Pain Psychologically

One of the goals of rigorous science is to disentangle various causes so we can establish exactly where the lines of cause and effect are. In medicine this allows us to then optimize the real causes (what aspect of treatments actually work) and eliminate anything unnecessary.

Eliminating the unnecessary is more than just about efficiency – every intervention in medicine has a potential risk, so this is also about risk reduction.

It often seems to me that the goal of “alternative” medicine is to blur the lines of cause and effect, to exploit non-specific effects in order to promote a useless but profitable ritual (acupuncture comes to mind).

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Posted in: Clinical Trials, Neuroscience/Mental Health

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Osteopathy in the NICU: False Claims and False Dichotomies

I would like to preface this post by stating that I have worked with many DOs (Doctors of Osteopathy), and I have helped train many pediatric residents with DO degrees. I have found no difference in the overall quality of the training these students have received, and some of the very best clinicians I have ever worked with have been DOs. I would never prejudice my assessment or opinion of a physician based on whether they have an MD or a DO after their name.

Now, on to the discussion at hand.

I recently stumbled upon an article entitled, “Effect of osteopathic manipulative treatment on length of stay in a population of preterm infants: a randomized controlled trial”. There is nothing particularly exciting or interesting about this study, as there have been many published on the use of osteopathic manipulative therapy (OMT) in children. There aren’t that many RCTs, however, and this particular one, although published in the open-access BioMed Central Pediatrics (impact factor 1.98), was chosen to be included in AAP Grand Rounds. AAP Grand Rounds is a publication put out by the American Academy of Pediatrics (AAP) to help pediatricians “Stay current and save time with monthly critical, evidence-based summaries of clinical content from nearly 100 journals.” Because the AAP found this important enough for mention in this widely read publication, with a distribution of 19,000 (source: AAP, 2014), I thought it would be interesting to take a closer look at it. I am also interested in the very odd existence of the two, distinct paths to becoming a physician in this country, osteopathic and traditional medical school training. The distinction between the two is rarely discussed, even within the halls of academia or in our health care centers. That’s not to say that the topic isn’t discussed at all (in fact it was highlighted very recently right here on SBM), it has just remained a somewhat politically incorrect subject, sliding mostly under the radar. Having worked with and trained pediatricians with osteopathic degrees, I can tell you that discussions about this are considered taboo. This is primarily because osteopathic physicians have become mainstreamed over time (see below), and discussing the validity of the existence of their “specialness” is an awkward proposition. After taking a look at the paper in question, I’ll address this issue some more as I think it deserves additional attention.

Effect of osteopathic manipulative treatment on length of stay in a population of preterm infants: a randomized controlled trial.

This was a single-blinded RCT conducted at Santo Spirito Hospital in Pescara, Italy to explore whether OMT could shorten the length of stay among premature infants in their neonatal ICU (NICU). Secondary outcomes studied were the differences in daily weight gain and total cost of the NICU stay.

I’ll discuss the methods in a moment, but first let’s review the results.
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Posted in: Clinical Trials

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Fighting Against Evidence

For the past 17 years Edge magazine has put an interesting question to a group of people they consider to be smart public intellectuals. This year’s question is: What Scientific Idea is Ready for Retirement? Several of the answers display, in my opinion, a hostility toward science itself. Two in particular aim their sights at science in medicine, the first by Dean Ornish, who takes issue with large randomized controlled clinical trials, and the second by Gary Klein, who has a beef with evidence-based medicine.

These responses do not come out of nowhere. The “alternative medicine” meme that has taken hold in the last few decades (a triumph of slick marketing over reason) is all about creating a double standard. There is regular medicine which needs to justify itself with rigorous science, and then there is alternative medicine, where the rules of evidence bend to the needs of the guru or snake oil salesperson.

We have been hearing arguments from alternative medicine proponents for years now for why the strict rules of science need to be relaxed or expanded. Andrew Weil has advocated for the use of “uncontrolled clinical observations,” (also known as anecdotes). David Katz advocates for a “more fluid concept of evidence.” Dr. Oz went as far as advocating outright medical relativism, saying. “You find the arguments that support your data, and it’s my fact versus your fact.” (more…)

Posted in: Clinical Trials, Science and Medicine

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Urinary Tract Infections Cause Depression. Directors Cut.*

As some may know I am infectious disease doctor. Urinary tract infections (UTI) butter my bread. Figuratively speaking. There is an enormous amount known about the pathophysiology of UTI’s. It is both a common and complex problem. But for all our knowledge, chronic and recurrent UTI’s remain a vexing issue for the patient and the doctor.

One reason people develop recurrent UTI’s is not because of altered chi along meridians altered by needles stuck in the skin distant from the bladder. That would be ridiculous. I like reasoning from basic principles. Given what we know about anatomy, physiology and microbiology, how might acupuncture interfere with the development of a urinary tract infection? Would it prevent colonization with pathogenic E. coli? Prevent retrograde travel of bacteria up the urethra into the bladder? Stop E. coli from binding to uroepithelial cells? Have a bactericidal or bacteriostatic effect?

None of the above seem likely. To my mind, postulating any of the above as a potential mechanism for acupuncture as a preventative for UTI’s would be ludicrous. And spare me your Boosting the Immune System, a concept that exists as a marketing tool, not a useful therapeutic intervention. My boss used to say that many an academic career floundered on attempting to prevent and treat UTI’s using an immune system approach. With some exceptions, and there are always exceptions, recurrent UTI’s in normal humans are usually due to anatomic or microbiological anomalies.

Despite its popularity, it is clear that acupuncture is not based on reality and, like all pseudo-medicine, only has demonstrable efficacy in poorly-designed studies. Acupuncture displays the usual progression of all pseudo-medicines. Increasingly-well-done studies show decreasing effect until a study that removes all bias shows it to be no better than placebo. Which one would expect for an intervention based on fantasy. Prior plausibility (the toy boat of SBM, try saying it three times very fast) would predict that acupuncture is worthless. And that should be acupunctures, all 6 styles are an elaborate ritual with no more likelihood of efficacy than the superstitions in a Budweiser commercial. (more…)

Posted in: Acupuncture, Clinical Trials, Traditional Chinese Medicine

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Stanislaw Burzynski: Using 1990s techniques to battle the FDA today

It figures that I couldn’t go three weeks into 2014 without the topic of Stanislaw Burzynski rearing its ugly head. I had hoped to make it to February or even beyond before feeling the gravitational tug of the wretched hive of ignominious and unethical behavior, but here we are, only 20 days into the new year. So be it.

2013 finished with serious setbacks for Stanislaw Burzynski and his unproven cancer treatment that he dubbed “antineoplastons” (ANPs) way back in the early 1970s. As you might recall, in November, two things happened. First, the FDA released its initial reports on its inspection of the Burzynski Clinic and Burzynski Research Institute (BRI) carried out from January to March 2013. They were damning in the extreme, pointing out the shoddy operating methods of the institutional review board (IRB) used by the BRI to approve and oversee Burzynski’s “clinical trials” (and I use the term loosely) of ANPs. Violations included using expedited approvals to review single patient protocols, something so far outside the purview of what the expedited approval process was intended for, namely approving minor tweaks to human subjects research protocols without requiring a full meeting of the IRB, that the FDA called Burzynski out for it. Other violations included failure to report serious adverse events (SAEs) and adverse events (AEs) to the FDA and/or the IRB, failure to follow proper informed consent procedures, failure to determine that risks to subjects were minimized and that risks to subjects were reasonable in relation to anticipated benefits, if any, and a lot of other violations, which are listed in my previous post on the subject. (more…)

Posted in: Cancer, Clinical Trials, Politics and Regulation

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Acupuncture Whac-a-Mole ™

Those who cannot remember the past are condemned to repeat it.
- George Santayana

Most people don’t have that willingness to break bad habits. They have a lot of excuses and they continue to produce bad clinical studies.
- Carlos Santana (Well, not the last 4 words.)

One is a guitar player, one is a philosopher. I get them confused.

I think George was in charge of SCAM research at the NIH. It was Dr. Gorski who first used the term Whac-a-Mole to describe what we do. The same badly-done studies are done over and over and misrepresented over and over, with only very minor variations on a theme. This is especially true of acupuncture, the most extensively studied pseudo-medicine in search of something, anything, for which it might be effective. They are still searching.

I loved going mano-a-mano with my kids when they were younger on the Whac-a-Mole machine in the Seaside arcade followed by root beer and elephant ears. It was the last time I beat either of them at any athletic endeavor. So I enjoy Whac-a-Mole, with mechanical rodents or bad research. (more…)

Posted in: Acupuncture, Clinical Trials, Critical Thinking, Science and Medicine

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Vitamin E for Alzheimer’s

Recently you may have seen headlines like “Vitamin E slows decline in patients with mild Alzheimer’s” or “There’s still no cure for Alzheimer’s disease, but the latest hope for slowing its progression is already on drugstore shelves.” They were referring to an article in the January 1, 2014 issue of the Journal of the American Medical Association (JAMA) announcing the results of the TEAM-AD VA Cooperative Randomized Trial of vitamin E and memantine (Namenda) for Alzheimer’s disease (AD).

The study attracted a lot of media attention. Most of the news reports I have seen were accurate and cautious, explaining the nuances of the study rather than suggesting that everyone should run out and buy vitamin E; but I wouldn’t be surprised to learn that a lot of readers ignored the fine print and did just that. It would be interesting to track sales of vitamin E and see if there was a bump following the publicity.

We know of no treatment that will delay, prevent or cure Alzheimer’s disease, or that affects the underlying disease process. It’s a tragic, frustrating disease that takes away the very things that make us who we are: memory and personality. It is affecting more and more people as the numbers of elderly increase. Available prescription medications are only modestly effective in slowing functional decline and delaying the need for institutionalization. They are expensive, they don’t help everyone, and when they do help, they only help for a limited time. It is very exciting to think an inexpensive vitamin could help patients with mild to moderate AD, but we must resist the temptation to read too much into this study. (more…)

Posted in: Clinical Trials, Herbs & Supplements, Neuroscience/Mental Health

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