Aug 08 2007

Using Unproven Therapies

An SGU listener sent me the following question;

“My question is this: might it not be reasonable for a skeptical, rational-thinking individual to turn to an herbal remedy or other medication which has not made it through this rigorous vetting process, and which has only anecdotal or preliminary evidence supporting its use, if they are desperate for some treatment (any treatment), and if evidence-based medicine has nothing to offer them?”

The short answer is yes, but this deserves a detailed explanation. The piece that is missing from the question above (a piece that is missing from evidence-based medicine) is plausibility. Both evidence and scientific plausibility should determine the hierarchy of treatments that are offered by ethical practitioners.

Modern medicine does not have a perfect treatment for all diseases and ailments – far from it. One of the biggest challenges facing a scientific practitioner is determining what to do for a patient when an obvious proven therapy is not available. There are many conceptual rules that help guide the approach to such situations. One very important rule is to carefully consider risk vs benefit of any intervention (or non-intervention).

Another helpful concept is to begin with the treatment or intervention that is backed by the most evidence and plausibility and then work your way down the ladder of scientific support only as needed. In other words, if there is a treatment for a particular disease that is supported by class I (placebo controlled, randomized clinical trials) evidence that clearly shows it is safe and effective (has a very favorable risk vs benefit ratio), then a rational, ethical practitioner should offer that treatment first.

If, however, such class I treatments do not exist, or the patient cannot take the treatment for some reason, or such treatment have already failed – then it is reasonable to go down the ladder one step and offer a treatment that has some evidence of safety and effectiveness, even if the evidence is not definitive. Such a treatment should also be scientifically plausible.

If a treatment with weak evidence is not available or had not worked, then it is reasonable to use a treatment that has some virtue to recommend it. The treatment may be known to be extremely benign and safe, and therefore there is little risk in trying it, or there may be only anecdotal evidence of it’s effectiveness. But at this stage of evidence, there really needs to be some scientific plausibility – some prior probability that the treatment will work safely.

This consideration – that of scientific plausibility – is often neglected. It is important because without it there can be an almost unlimited number of possible treatments to try. Picking treatments essentially at random (which is functionally the case when choosing a treatment based upon quirky experience, ideology, or exposure) is not a rational approach. The reason gets back to risk vs benefit. There needs to be some reason to think that the treatment may work and also some reason to think that it will be safe, otherwise you are as likely (and perhaps more likely) to cause harm than good.

At its core, medicine is a game of probability. We can never know for sure what a specific treatment will do to a patient. We make our best statistical judgment based upon solid scientific evidence, and we can get very good at judging probability when we have the evidence, but in the end all treatment is a matter of trial and error or just playing the odds.

So when dealing with treatments or interventions for which we have a paucity of evidence it must be recognized that there may be unknown risks as well as unknown benefits. It also must be recognized that anecdotal evidence is extremely weak, and often misleading, and we should not put much faith in it.

Which brings us back to scientific plausibility. In the absence of solid empirical evidence, what makes scientific sense based upon our basic science knowledge of biology and disease is likely to be our best indicator of risk vs benefit. I think that scientific plausibility is far better than anecdotal evidence, in fact. In other words, I would have more confidence in a treatment that made scientific sense but for which we have no evidence than a treatment that made no scientific sense and for which there was anecdotal evidence.

Further, there needs to be a limit on how far down the ladder of plausibility and evidence we are willing ethically to go. I think there needs to be a minimum bar below which there be the dragons of substandard and unethical medicine. This includes treatments for which there is reliable evidence for lack of efficacy or unacceptable risks. It should also include treatments that have extreme scientific implausibility (like homeopathy or therapeutic touch, for example).

Another point to consider is that at the lower end of the evidence ladder treatments should be given, if at all possible, in the context of a research protocol. There exists in medicine a highly developed system for the ethical conduct of research on human subjects. This includes rules for estimating risk, carefully tracking outcomes, and giving full informed consent. I am against giving what are essentially experimental treatments outside the confines of this ethical system.

An ethical scientific practitioner must put all of this together to individualize their recommended intervention for a specific patient. So-called complementary and alternative practitioners, in my experience with them, and by their own account, practice largely below the line of scientific evidence and plausibility. They also violate the hierarchy of scientific treatments by going to unproven therapies when better therapies are available.

Even for practitioners who are philosophically scientific, there is a risk to complacency in using speculative treatments. Specifically, this complacency discourages appropriate clinical research. Practitioners, convinced by their own anecdotal experience, are often too comfortable using treatments that should be considered experimental. The ultimate solution to the dilemma of what to do in the absence of reliable scientific evidence is research. Therefore, whenever possible patients should be referred to clinical studies to get experimental treatments, rather than just getting the experimental treatment outside of a trial.

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