Conventional medicine, 'alternative' treatments, and the ethics of research with humans.

A little while ago, PalMD put up a post at Whitecoat Underground about the current state of the National Center on Complementary and Alternative Medicine (NCCAM), especially at a moment in history when the federal government is spending loads of money (and thus maybe should be on the lookout for expenditures that might not be necessary) and when health care reform might actually happen. Pal wrote:

The whole idea of setting up such an agency is a bit quixotic---after all, the National Institutes of Health already study health science. .... Many, many studies have been funded which fail basic tests of plausibility and ethical propriety. Also, a huge percentage of the studies funded fail to ever publish their results. Still, some studies have been published, and more often than not, they find that the "alternative" modality being studied fails to behave better than placebo. That's probably the sole redeeming quality of the agency, but not enough to keep it open, as these studies could have been done under the auspices of the NIH.

Since I have not been a close follower of NCCAM, I figured I'd have a look at their website. (I was a wee bit apprehensive given the trauma the website inflicted on Dr. Benway.) Whether of not the agency you think the agency ought to exist, it does lay out some relevant terminology very clearly. For example, what is CAM?

CAM is a group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medicine. Complementary medicine is used together with conventional medicine, and alternative medicine is used in place of conventional medicine. Conventional medicine is medicine as practiced by holders of M.D. (medical doctor) or D.O. (doctor of osteopathy) degrees and by their allied health professionals, such as physical therapists, psychologists, and registered nurses. Some health care providers practice both CAM and conventional medicine.

The list of practices that are considered CAM changes continually, as those therapies that are proven to be safe and effective become adopted into conventional health care and as new approaches to health care emerge.

And, what is NCCAM's role in the field of CAM?

The National Center for Complementary and Alternative Medicine (NCCAM) is the Federal Government's lead agency for scientific research on CAM. NCCAM's mission is to explore complementary and alternative healing practices in the context of rigorous science, train CAM researchers, and disseminate authoritative information to the public and professionals.

So, the practices people use to deal with illness, injury, or health maintenance can be divided into two piles: those that are accepted by conventional medicine (as practiced in the U.S. at this point in history - NCCAM is an agency of the U.S. federal government), and those that are not accepted by conventional medicine.

Those two piles correspond at least approximately to another distinction: practices whose safety and efficacy are well-supported by empirical evidence, and practices whose safety and efficacy are not so supported.

It's worth pointing out here that an intervention whose safety and efficacy are not currently supported by empirical evidence may find such support if the relevant research is done. In the absence of empirical evidence one way or another, it may be the case that we just don't know - at which point, there may be good reason to set about getting the empirical evidence that would answer the question for us. (There may also be good reasons to be cautious in trying to get this empirical evidence; more on this below.)

It also seems likely that there are some parts of conventional medical practice that are not driven entirely by the evidence from placebo-controlled double-blind clinical trials. There are lots of pieces of the interaction between patient and health care provider that feel more like unscripted interpersonal interaction than well-tested scientific intervention. In a word, these conventional practices may be conventions, practiced because that's what people in the health care community seem to do (and it seems to work reasonably well). Possibly these conventions have no effect whatsoever on patient outcomes. If they do, though, presumably there might be some value in mounting empirical trials to determine what kind of effects they have.

Nonetheless, the idea is that conventional medicine is striving toward developing an arsenal of health care interventions that are grounded in good empirical evidence - so much so that once an "alternative" treatment gets this kind of grounding, it is taken on board by practitioners of conventional medicine.

So why not take stock of all the alternative treatments out there, set up clinical trials, and get the evidence that will sort out the good from the bad?

The short answer is that clinical trials are experiments with human subjects, and there are ethical and regulatory constraints on the kinds of experiments you can conduct on humans. If the foreseeable risks to the human subjects of the experiment are great enough, or if they outweigh the foreseeable benefits to the human subjects, then you can't do the experiments - even if the knowledge they might generate would be really useful.

The NCCAM website actually has a pretty clear explanation of what a clinical trial is (and of the different phases of clinical experimentation). Here's how that site describes the possible benefits of being in a clinical trial:

• You will receive expert medical care.
• Your health will be closely watched throughout the study.
• Clinical trials can be one treatment or prevention option for a disease or condition.
• In some types of trials, you may be among the first to benefit from a new treatment or new knowledge about a current treatment.
• You will help others by helping to advance medical and scientific knowledge.

And here's how it describes the possible risks to being in a clinical trial:

There are possible risks to being in a clinical trial, as there are with any form of treatment and with illness itself. In a clinical trial:

• The treatment under study does not always turn out to be better than, or even as good as, standard treatment. The researchers hope that it is, but they need to do the study to find out for sure.
• The treatment may have side effects that are unknown to the researchers or different from what they expect.
• If you are in a randomized trial, you may be assigned to the control group, where you will not receive the treatment under study.
• Like standard treatments, the treatment under study may not work for everyone.
• Participation may require more tests and more visits or treatments than regular care.
• There may be costs to participate, and these costs may not all be covered by health insurance plans. Be sure to talk with the research team about any costs involved and your situation.

Depending on the disease or condition being treated, receiving an ineffective treatment can be a very big harm. Especially if there's a reasonably safe and effective treatment that's already part of the conventional medical practitioner's bag of tricks, the benefit of establishing the safety and efficacy of an unproven alternative may turn out to be quite small relative to the risks. Of course, if the established treatment is not so effective for particular patient populations, or if the side-effects for particular patient populations are very serious, that may chance the risk-benefit calculus. But the safety of the human subjects of the research is prioritized - which means, in some cases, the (limited) information we have makes us judge the costs of building more complete knowledge are just too high to warrant proceeding with the research.

Going forward with a clinical trial that we have good reason to think would be harmful to the human subjects crosses the line ethically. I think there's also a feeling that plausibility ought to play a role in the evaluation of whether a clinical trial is ethical. Plausibility is tricky - it's a question about whether a particular kind of intervention could possibly be effective given the current state of our understanding (of human biology, of this sort of intervention, etc.). Clearly, the current state of our understanding is incomplete and subject to revision; this is why scientists are still involved in conducting research.

Does "X could plausibly treat condition A" mean that there must be some clear mechanism by which X might act to cure or improve condition A? There have been compounds whose efficacy was widely accepted before we had anything like a detailed understanding of the mechanisms by which they worked (think aspirin). Does "X could plausibly treat condition A" mean that there already exists a body of empirical data demonstrating its efficacy? If this were the standard, no compound that wasn't already being used by a significant number of people could ever make it to clinical trials.

Plausibility does play some sort of role in the evaluation of the risks an intervention might pose to human subjects. As I've discussed before, researchers have to make their best guesses of likelihood of benefit and likelihood of harm given the knowledge that exists. Since humans are subjects of the research (and because we recognize that human subjects are entitled to certain protections), the current state of the knowledge might rule out research to build a new piece of knowledge on the basis that building that new knowledge might come at too high a price for the human subjects.

It's worth noting, though, that at least some of the "alternative" treatments that turn up in NCCAM studies involve stuff a good number of people do everyday that they might not consider a medical treatment - drinking cranberry juice or herb tea, eating tofu, getting a massage, meditating, doing yoga. At least from my vantage point in the land of veggie restaurants and yoga studios, I don't imagine that these "alternative treatments" are feared to be harmful in themselves. Rather, they are probably viewed as "risky" to the extent that they may replace medical interventions that are well-grounded in empirical evidence - or to the extent that funding to study them in clinical trials might waste funds that would be better directed to studying interventions judged more likely to be effective.

There are interesting questions here about the challenges of distinguishing the causal impacts of all the kinds of things people actually do with their bodies (ingesting medications, ingesting food, exercising, sleeping, getting stressed, getting germy) on the state of their health. Our presumptions about which of these things are likely to have the biggest effects - and the medical community's presumptions - may shift in the light of new information. Sometimes this information comes from well-controlled experiments, but sometimes it might come from other places (like our own personal experience or anecdotes from others). It's also worth asking whether some of the causal impacts of the things people do are judged as probably-not-that-important because it's wicked hard to control them in experiments.

Let me close with a question for the biomedical researchers in the audience: What is the practical difference in getting a clinical trial approved and funded through NCCAM versus NIH? Could the sorts of research overseen by NCCAM be folded into NIH without too much trouble? (If not, why not?)