In 1998 Andrew Wakefield and 11 other co-authors published a study with the unremarkable title: Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Such a title would hardly grab a science journalist’s attention, but the small study sparked widespread hysteria about a possible connection between the mumps-measles-rubella (MMR) vaccine and autism spectrum disorder (ASD).
The study itself has not stood the test of time. The results could not be replicated by other labs. A decade of subsequent research has sufficiently cleared the MMR vaccine of any connection to ASD. The lab used to search for measles virus in the guts of the study subjects has been shown to have used flawed techniques, resulting in false positives (from the Autism Omnibus testimony, and here is a quick summary). There does not appear to be any association between autism and a GI disorder.
But it’s OK to be wrong in science. There is no expectation that every potential finding will turn out to be true – in fact it is expected that most new finding will eventually be found to be false. That’s the nature of investigating the unknown. No harm no foul.
A recent series of article in the Proceedings of the National Academy of Sciences (PNAS) discusses the role of evolutionary biology in modern medicine. The authors collectively make a forceful point – medicine is an applied science. It is based upon a number of basic sciences, and one of those basic sciences is evolution.
The most obvious example is bacterial antibiotic resistance. Antibiotics place a selective pressure on a bacterial population, often resulting in the emergence of resistant strains. Understanding this “evolutionary arms race” between bacteria and antibiotics allows us to develop strategies for minimizing resistance.
But there are less obvious ways in which evolutionary principles apply to infectious diseases. It has been known for a long time that sickle-cell trait provides resistance to malaria (the blood cells are less hospitable to the P. falciparum protozoan parasite that is one cause of malaria). This explains the persistence of sickle cell disease in populations where malaria is endemic.
Ever since news of the harmful effects of tobacco smoke hit the public consciousess around the middle of the 20th century the tobacco industry and others have been looking for a “healthy” alternative. Are e-cigarettes just latest in a list of failed attempts to make smoking safe?
In case you are a new visitor to our planet (welcome) using tobacco products has been determined to be a significant risk factor in developing certain kinds of lung cancer and vascular disease, including strokes and heart attacks (the top three killers). The tobacco industry initially tried desperately to deny or downplay the scientific evidence for the health risks of smoking, engaging in a campaign of doubt and confusion, but those efforts ultimately failed.
Some companies marketed light, low tar, and filtered cigarettes with the claim, direct or implied, that they were a more healthful alternative to regular cigarettes. However, there has never been convincing evidence that such cigarettes are less of a health risk. Still, the marketing stuck and now 90% of all cigarettes sold are filtered.
The problem with the Western diet is not one of deficiency, but one of excess. We get too much of a good thing – too many calories, too much of the wrong kind of fat, and too much salt. As a result obesity, diabetes, and hypertension are growing health problems.
There also does not appear to be an easy solution – voluntary diets founded primarily on will power are notoriously ineffective in the long term. Add to that is the marketplace of misinformation that makes it challenging for the average person to even know where to apply their (largely ineffective) will power.
It can be argued that this is partly a failure, or an unintended consequence, of market forces. Food products that provide cheap calories and are tasty (sweet, fatty, or salty) sell well and provide market incentives to sell such products. Consumers then get spoiled by the cheap abundance of tempting foods, even to the point that our perspective on appropriate portion sizes have been super-sized.
In the most recent issue of The Journal of clinical Oncology is a study comparing acupuncture to Effexor in the treatment of vasomotor symptoms (hot flashes) in women with breast cancer who cannot take hormone replacement therapy. The study found that the two treatments are equivalent, with longer duration and fewer side effects from acupuncture. However, the study is designed as a pilot study (very preliminary) and therefore the conclusions are highly unreliable – given prior research, this raises the question as to why the study was performed at all.
The study included only 50 women, which is a small number for a clinical trial and alone means this is at best a preliminary study. There were 25 women randomized to one of two arms – either acupuncture or Effexor (which is standard treatment for vasomotor symptoms in women with breast cancer). However, the two arms were not blinded in any way, and there was no acupuncture control group – no sham or placebo acupuncture.
It is unclear why the researchers undertook a small unblinded study such as this, given that previous studies were better designed.
Another one bites the dust.
The National Center for Complementary and Alternative Medicine (NCCAM) is generally a waste of taxpayer money, but they have sponsored several well-designed large trials of popular herbal supplements. And one by one these studies have shown these popular products, such as echinacea for the common cold, to be ineffective.
To add to the list, published in JAMA this week are the results of the largest and longest trial to date of Gingko biloba for the improvement of cognitive function and to treat, prevent, or reduce the effects of Alzheimers disease or other dementia. The results of the study are completely negative.
The study was very rigorous – a consensus trial designed to address all the criticisms of prior smaller studies. It was a direct comparison of Gingko biloba at 120mg twice a day, double blind, randomized, multi-center trial involving 3019 subjects aged 72-96 for a median of 6.1 years. Subjects were followed with standardized tests of cognitive function.
Peter Lipson reported Monday about new research suggesting that Multiple Sclerosis may be caused by venous blockage. He correctly characterized some of the hype surrounding this story as “irrational exuberance.”
This is a phenomenon all too common in the media – taking the preliminary research of an individual or group (always presented as a maverick) and declaring it a “stunning breakthrough,” combined with the ubiquitous personal anecdote of someone “saved” by the new treatment.
The medical community, meanwhile, responds with appropriate caution and healthy skepticism. Looks interesting – let’s see some more research. There is a reason for such a response from experts – experience.
The primary reason that I and others favor science-based medicine, as opposed to the alternatives, is that science works. As Carl Sagan said, “Science delivers the good.” Science has other virtues – it is transparent and self-corrective also.
Recently two unrelated news items have provided an opportunity to compare a scientific vs a pseudoscientific approach to the same problem – that of communicating to patients who are locked-in.
Locked-in describes those who suffer from an injury or neurological disease that mostly paralyzes them, so that they cannot move or communicate. One scenario that leads to a locked-in state is a brainstem stroke, where patients are paralyzed below the eyes – they can only blink and move their eyes, but nothing else. Widespread trauma can lead to a similar situation. ALS, which leads to progressive loss of motor neurons, can also result in total or near total paralysis.
Several weeks ago I wrote the first in a brief series of posts discussing the different types of evidence used in medicine. In that post I discussed the role of correlation in determining cause and effect.
In this post I will discuss the basic features of an experimental study, which can sere as a check-list in evaluating the quality of a clinical trial.
Medical studies can be divided into two main categories – pre-clinical or basic science studies, and clinical studies. Basic science studies involve looking at how parts of the biological system work and how they can be manipulated. They typically involve so-called in vitro studies (literally in glass) – using test tubes, petri dishes, genetic sequencers, etc. Or they can involve animal studies.
Clinical trials involve people. They are further divided into two main categories – observational studies and experimental studies. I will be discussing experimental studies in this post – studies in which an intervention is done to study subjects. Observational studies, on the other hand, look at what is happening or what has happened in the world, but does not involve any intervention.
Many parents of children with autism have expressed to me their dismay that the anti-vaccine lobby is sucking all the oxygen out of the room for autism awareness. They feel that just being a parent of a child with autism makes others assume that they are anti-vaccine. They also worry that resources and attention are being diverted from promising legitimate research because of all the attention being paid to the failed vaccine hypothesis.
So it is good to occasionally focus on mainstream autism research to show that progress is being made, despite the unfortunate anti-vaccine sideshow.
A recent study published in the latest issue of Pediatrics shows that early intervention in toddlers with autism can have significant benefits. The study is a randomized controlled trial of the Early Start Denver Model compared to conventional treatment in 18-30 month old children with a diagnosis of autism spectrum disorder (ASD). The study is a reasonable size for this kind of intervention – 48 children were randomized – and this is sufficiently powered to get statistical significance. But it should be noted this is still a smallish study and replication to confirm the results is welcome.
Another potential weakness is that the control group was “referral to community providers for intervention commonly available in the community.” Therefore the control group was not standardized and it’s possible this group was sub-optimally treated. Further, while the groups were randomized they were not blinded.