Saturday, March 20, 2010

Science-Based Medicine

What's the difference between science-based medicine and evidence-based medicine?  I never realized there was a difference. But according to this post by Steven Novella, the difference is in the precise role of plausibility, or prior probability. He makes some interesting points.

Plausibility is essentially an application of existing basic and clinical science to a new hypothesis, to give us an idea of how likely it is to be true. We are not starting from scratch with each new question – which would foolishly ignore over a century of hard-won biological and medical knowledge. Considering plausibility helps us to interpret the clinical literature, and also to establish research priorities. But plausibility is not the ultimate arbiter of clinical truth – it must be put into context with clinical evidence, just as clinical evidence must be put into the context of scientific plausibility.

He lists three categories of plausibility:

The first category are those treatments with a known mechanism or mechanisms of action that should, according to our existing models, produce a certain clinical effect. ... We may also add to this category treatments for which there is anecdotal or preliminary evidence for efficacy – clinical plausibility.
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The next broad category is not implausible, but neutral or unknown with respect to plausibility. For such treatments we have no particular reason to think that they should work, but no reason to suspect that they do not or cannot work either.
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But there is a third category in the plausibility spectrum – treatments that are inherently implausible. These are treatments that not only lack a known mechanism of action, they violate basic laws of science.

Novella makes a very good point here, that it would be foolish to ignore the medical knowledge we've accumulated when attempting to evaluate a new claim. It's always possible that our existing knowledge is wrong - this concept is fundamental to the scientific method - but that doesn't make it likely. And if you intend to overthrow established science, you'd better have very strong evidence indeed.

Homeopathy violates the law of mass action (a basic principle of chemistry), the laws of thermodynamics (extreme dilutions maintaining the chemical “memory” of other substances), and all of our notions of bioavailability and pharmacokinetics.

Homeopaths therefore substitute any notion of chemical activity with a vague claim about “energy” – but this just puts homeopathy in the category of energy medicine, which is just as implausible. Invoking an unknown fundamental energy of the universe is not a trivial assumption. Centuries of study have failed to discover such an energy, and our models of biology and physiology have made such notions unnecessary, resulting in the discarding of “life energy” as a scientific idea over a century ago.

Essentially any claim that is the functional equivalent to saying “it’s magic” and would, by necessity, require the rewriting not only of our medical texts, but physics, chemistry, and biology, can reasonably be considered, not just unknown, but implausible.

"Implausible" does not mean "impossible," of course - at least, not theoretically. Theoretically, everything we think we know about science could be wrong. But that certainly shouldn't be our assumption. And it should take very, very strong evidence to convince us otherwise.

Having said that – even the most implausible claim can still prove itself with sufficient clinical evidence. If homeopathy actually worked, it could be demonstrated through repeated rigorous clinical studies (something which has never happened). Admittedly, the bar for such evidence would be as high as the prior implausibility of the claim – which is very high – but if it really worked, that bar of evidence should theoretically be reachable. In that very hypothetical situation, the results would be extremely intriguing – clearly there would be something fundamental missing from our understanding of the relevant areas of science – a situation that often results in Nobel prizes.

There are always powerful defenders of the status quo, in science just like everywhere else. But the advantage in science - one of the advantages - is that there are equally powerful forces on the other side. Science reserves its highest rewards - fame, money, and position - to those who successfully overthrow established thinking. So, although there's often an incentive to go along with the crowd (just as there is everywhere), there's also a strong incentive among scientists to buck it.

Of course, such researchers still have to be right. You can find all sorts of individual scientists with bizarre ideas. That's a good thing. But the vast majority of them are almost certainly wrong. It's not likely, not at all, that established science is in error (current thinking on cutting-edge science is different, of course). It does happen, and every scientist hopes to be one of those few heroes of the field. And the rest of us also enjoy rooting for the underdog, don't we? It would be neat if some of those things were right. But without very good scientific evidence, confirmed in multiple independent studies, we should remain skeptical.

The mainstream, the scientific consensus, will change if the evidence is there. It happened with the idea that bacteria cause ulcers. It happened with the idea that prions cause Mad Cow Disease. And it will undoubtedly happen again. But the odds are low, especially for those extremely implausible ideas that would require a complete rewrite of our scientific knowledge.

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