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Whassup with phantom-limb treatment?

OK, here’s something that is completely baffling me. I read this article by John Colapinto on the neuroscientist V. S. Ramachandran, who’s famous for his innovative treatment for “phantom limb” pain:

His first subject was a young man who a decade earlier had crashed his motorcycle and torn from his spinal column the nerves supplying the left arm. After keeping the useless arm in a sling for a year, the man had the arm amputated above the elbow. Ever since, he had felt unremitting cramping in the phantom limb, as though it were immobilized in an awkward position. . . . Ramachandram positioned a twenty-inch-by-twenty-inch drugstore mirror . . . and told him to place his intact right arm on one side of the mirror and his stump on the other. He told the man to arrange the mirror so that the reflection created the illusion that his intact arm was the continuation of the amputated one. The Ramachandran asked the man to move his right and left arms . . . “Oh, my God!” the man began to shout. . . . For the first time in ten years, the patient could feel his phantom limb “moving,” and the cramping pain was instantly relieved. After the man had used the mirror therapy ten minutes a day for a month, his phantom limb shrank . . .

Ramachandran conducted the experiment on eight other amputees and published the results in Nature, in 1995. In all but one patient, phantom hands that had been balled into painful fists opened, and phantom arms that had stiffened into agonizing contortions straightened. . . .

So far, so good. But then the story continues:

Dr. Jack Tsao, a neurologist for the U.S. Navy . . . read Ramachandran’s Nature paper on mirror therapy for phantom-limb pain. . . . Several years later, in 2004, Tsao began working at Walter Reed Military Hospital, where he saw hundreds of soldiers with amputations returning from Iraq and Afghanistan. Ninety percent of them had phantom-limb pain, and Tsao, noting that the painkillers routinely prescribed for the condition were ineffective, suggested mirror therapy. “We had a lot of skepticism from the people at the hospital, my colleagues as well as the amputee subjects themselves,” Tsao said. But in a clinical trial of eighteen service members with lower-limb amputations . . . the six who used the mirror reported that their pain decreased [with no corresponding improvement in the control groups] . . . Tsao published his results in the New England Journal of Medicine, in 2007. “The people who really got completely pain-free remain so, two years later,” said Tsao, who is currently conducting a study involving mirror therapy on upper-limb amputees at Walter Reed.

At first, this sounded perfectly reasonable: Bold new treatment is dismissed by skeptics but then is proved to be a winner in a clinical trial. But . . . wait a minute! I have some questions:

1. Ramachandran published his definitive paper in 1995 in a widely-circulated journal. Why did his mirror therapy not become the standard approach, especially given that “the painkillers routinely prescribed for the condition were ineffective”? Why were these ineffective painkillers “routinely prescribed” at all?

2. When Tsao finally got around to trying a therapy that had been published nine years before why did they have “a lot of skepticism from the people at the hospital”?

3. If Tsao saw “hundreds of soldiers” with phantom-limb pain, why did he try the already-published mirror therapy on only 18 of them?

4. How come, in 2009, two years after his paper in the New England Journal of Medicine–and fourteen years after Ramachandran’s original paper in Nature–even now, Tsao is “currently conducting a study involving mirror therapy”? Why isn’t he doing mirror therapy on everybody?

Ok, maybe I have the answer to the last question: Maybe Tsao’s current (as of 2009) study is of different variants of mirror therapy. That is, maybe he is doing it on everybody, just in different ways. That would make sense.

But I don’t understand items 1,2,3 above at all. There must be some part of the story that I’m missing. Perhaps someone could explain?

P.S. More here.

21 Comments

  1. jsalvatier says:

    My impression is that medicine is quite irrational, frequently pushing practices that have no benefit and resisting practices that have a lot of benefit. I'm not sure why medicine is like this. My most plausible explanation is that people have a tendency to think of the human body as far simpler than it is because its us and we're used to dealing with it all the time. It seems like something which should be easy to deal with in all contexts, even though the internals are very complex and we're not used to dealing with them at all.

  2. Manoel Galdino says:

    You probaly don't know, but in the TV show House, Hugh Laurie plays the main character, named Dr. House. Well, in 6th season, House used this treatment in one of the episodes, and it worked.

    It appeared a well knonw fact by Dr. House, not a new, fancy, technique. On the other hand, the "patient" didn't know the treatment and nor his (other) doctors.

  3. K? O'Rourke says:

    Sometimes too slow, sometimes to quick.

    In fact, there is a whole research field dedicated to figuring out how to get the timing just right.

    A link to one resaercher in that field http://www.research.uottawa.ca/chairs-details_19….

    Also a search will find some cummulative meta-analysis that attempted to identify – post hoc – when treatments should have been adopted.

    K?

  4. Bob Carpenter says:

    A bold new form of statistical inference, let's call it B, is proposed and shown to be effective. Surprisingly, more than a decade later, many statisticians still use older methodologies (1). When practitioner Y proposes B for a real problem, Y is met with skepticism from Y's colleagues (2). Y sees hundreds of problems that could benefit from B, but alas, only has time to fit and evaluate models for eighteen of them (3). Even more surprisingly, years after B was invented, statisticians are still doing research about the effectiveness of B (4).

  5. anon says:

    Very nice. But is B for Bayes, Bootstrap, or roBust variance estimates? – the story would fit all three.

  6. Kaiser says:

    I'm curious why only 6 out of 18 patients got the mirror treatment in the clinical trial. Were there 3 test groups? Also, was there an attempt to measure the placebo effect? (seems hard to accomplish since it can't be blinded but it seemed plausible that they observed a placebo effect.)

  7. Seth Roberts says:

    Answer to Question 2 (why a lot of skepticism?): Partly because the mirror treatment is quite different than conventional treatments (drugs). You see the same pattern in use of the ketogenic (high-fat) diet to control epilepsy. Using nutrition to fight disease isn't what doctors are taught. Partly because the skeptics hadn't read the original paper or had trouble understanding it.

  8. Andrew Gelman says:

    Seth:

    Sure, but the situations are different. For one thing, there's a long history of quack dietary claims, so any new dietary treatment has to be interpreted in that context. The phantom limb treatment seems unique.

  9. Jeff Lax says:

    2 out of 2 doctors I've asked agree:

    1. and 3. and 4. It's very labor intensive.
    2. Medicine is naturally conservative.
    4. continued – to deal with #2 and show people that despite the answer to #1,3,4, it's worth it. And also because he can probably publish it. Reason enough in our business.

  10. Andrew Gelman says:

    Wow–that's horrible! We often do a pretty crappy job at teaching, and that's our job. But medicine seems more important, somehow.

  11. gaddeswarup says:

    My impression: it was work in progress and worked for some people to some extent. There is a nice write up in the later half of "The Itch" by Atul Gawande:
    http://www.newyorker.com/reporting/2008/06/30/080

  12. I am thinking of Barnard and Fishers exact tests for 2×2 contingency tables.

    http://en.m.wikipedia.org/wiki/Barnard's_tes

  13. vic says:

    One major reason is that people have a hard time coming to terms with the fact that physical symptoms have mental causes (see Seth Robert's failure to recognize obvious placebo effects when reading the testimonials of multiple sclerosis patients who had undergone 'liberation' therapy on their neck veins).

  14. K? O'Rourke says:

    Andrew, in stats we have risk free math reasoning – so all those that can understand should accept math claims immediately.

    Thats almost never the case in medicine, though I really liked Bob's spin back to stats.

    The lack of the immediate acceptance of the claims for preference of Fisher's Exact test in randomized two group studies is though haunting.

    Now that its doable to simulate and plot the type error rates by the unknown nuisance control rate – that might change. (There was an early post about how to do better requires post-randomization or from Agresti the expectation of such post-randomization.)

    K?
    p.s. my first ever stats talk was

    Utilizing Computer Intensive Methods to "Concretize" Theorems and Principles from Statistics – Precisely. Department of Health Administration, University of Toronto, 1988. (the first example was Fisher's Exact test)

    and the second was about auditing evidence prior to adoption of new treatments

    Meta-Analysis: Auditing Scientific Projects and Method. University of Toronto, Department of Statistics Colloquim, 1989.

  15. Andrew Gelman says:

    Aslak:

    I hate hate hate all these so-called exact tests. As I've written many times (here on this blog and also in my 2003 article), these tests correspond to a reference distribution–a table with row and column margins fixed–that generally makes no sense. In all the studies I've ever seen, you'll only have one or zero margins constrained by the design. The only example I've ever seen of this design is Fisher's tea-tasting example.

    I'm happy to agree to the use of so-called exact tests for the tea-tasting example, as long as others agree that these tests make no sense in the vast vast majority of designs.

    Keith:

    Regarding your first paragraph above: All the math in the world won't save you if you're working with a model that doesn't make sense. As in much of the work on exact tests, including an large and pointless literature on computing exact distributions of discrete tables with constrained marginals. If only these people would look more carefully at the assumptions of their models!

  16. K? O'Rourke says:

    Agree Andrew, it is given you take the model as given that you get the risk free reasoning – the implications.

    As for more carefully looking at the assumptions, Fisher tried to be very clear about this – the randomization was done and responses were independent and the treatment is being assummed to have had absolutely no effect at all (Fisher's Null – just a labeling) and although the choice of what is "surprising" is arbitrary (shift in mean, increase in variance) it often is defined apriori.

    Rubin and Freedman have written about this visa vie Neyman's more general NULL and both or at least Freedman have prefered Neyman's – and then you would be free of Fisher's implications but stuck with Neyman's.

    But also with all wrong models operating characteristics may be worth looking at – and outside well controlled randomized experiments – I would fully agree type one error and plots of type one error versus nuisance parameters make no sense at all.

    K?

  17. mike Baxall says:

    Mirror therapy was first described by V.S. Ramachandran for treatment of phantom limb pain, but has since been proven in the treatment of complex regional pain syndrome (CRPS) / RSD, and stroke rehabilitation, as well as for hand and foot rehabilitation following an injury or surgery. http://www.mirrorboxtherapy.com is a good place to start; it has lots of information and a link to where you can purchase a mirror box.

    A folding mirror therapy box is a great tool in assisting home therapy, after a stroke or injury. Its light weight folds in seconds and can be taken anywhere. For more info google mirror box therapy.

  18. Mike Maltz says:

    Hasn't Big Pharma determined that it can attack the problem with a drug, perhaps the one used for restless leg syndrome? You can't patent a folding mirror. [Or am I too cynical?]

  19. Andrew Gelman says:

    Mike M.:

    Perhaps phantom-limb treatments can be monetized. Follow the link of the comment just above yours. Usually I delete comments that have a commercial link but this one actually seemed relevant to the discussion!

  20. I'd like to know the back story to mirror box therapy first being attempted. Because it seems quacky and divorced from intuition (until it actually works).