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Massage for AIDS

ResearchBlogging.orgI recently learned of a study entitled “Dominican Children with HIV not Receiving Antiretrovirals: Massage Therapy Influences their Behavior and Development.” It disturbed me, and I couldn’t get it out of my head. They’re massaging these kids but letting them die of AIDS? I went back and read the complete article, and it left me even more disturbed.

They studied 48 Dominican children ages 2-8 with untreated HIV/AIDS, randomizing them to receive twice weekly sessions of either massage or play therapy for 12 weeks. The abstract said that those in the massage group improved in self-help abilities and communication, and that children over the age of 6 showed a decrease in depressive/anxious behaviors and negative thoughts. That’s what the abstract said. The text revealed a more complex story.

One thing that may be irrelevant but that bothered me: there were several errors that should have been caught by an editor, a proofreader, a peer reviewer, or even a spell-checker:

• Caribbean was spelled “Carribean,”
• “…for enhancing varying behavioral and developmental domains” (I have no idea what this means).
• “A second objective of our work was to determine the absence of antiretroviral treatment on the impact of HIV infected Dominican children’s mood and behavior.” (I have trouble even guessing what they meant to say here.)
• “in helping reducing” instead of “in helping reduce”
• “interesting” where it should say “interestingly”
• The abstract referred to 20 minute sessions, but the text said 30 minutes.

When a journal overlooks errors like these, I always wonder if they’ve overlooked more serious errors of science or logic. In this case, it appears that they did.

Introduction.

The introduction usually provides a brief review of the literature and explains the rationale for doing the study. In this case, the rationale was not clear. They seemed to make two main claims for massage: enhancement of immune function and psychological/developmental effects. This study was not designed to assess immune function, but it suggested that improved immune function would improve psychological/developmental outcomes; in fact, it speculated about possible mechanisms for this.

They stated as a fact that massage improves immune function; they failed to acknowledge that the evidence is mixed. Some studies have shown an increase in certain parameters like natural killer cell counts, others have shown no benefits, like this study and this one involving HIV patients.

No study has shown that massage produces any objective improvement in outcome for HIV/AIDS patients.

There is research showing that massage improves outcome for premature babies, but a Cochrane review concluded, “Evidence that massage for preterm infants is of benefit for developmental outcomes is weak and does not warrant wider use of preterm infant massage.” Another Cochrane review of normal infants concluded, “The only evidence of a significant impact of massage on growth was obtained from a group of studies regarded to be at high risk of bias.”

Their stated hypothesis was “that Dominican pre-school age children infected with HIV would show improved mood, fewer behavioral problems, and enhanced development following massage therapy.” I don’t think they made a good case that such a hypothesis was plausible.

Methods

Each child had 30 minutes of one-on-one interaction with a trained nurse, who either administered a standardized massage protocol or the play therapy protocol, which consisted of giving the child a choice of coloring/drawing, playing with blocks, playing cards, or reading children’s books. Parents were present throughout, and they were interviewed to score the Child Behavior Checklist (CBCL) and Developmental Profile (DP-II).

Results

On the CBCL, on the empirically based scales used to evaluate children under the age of 5, there were no significant differences between the massage and the play groups. (The scales include emotionally reactive, anxious/depressed, somatic complaints, withdrawn, attention problems, aggressive behaviors, other problems and sleep problems.)

For children over the age of 6, they reported “significant” improvements for the massage group in
• anxious/depressed behaviors (p = .026)
• negative thoughts (p=0.059)
• overall internalizing scores (p=0.02)

Note that p=0.059 is above the usual cutoff of p=0.05 and would be reported as not significant by most researchers.

Their definition of significance seems to vary with whether it supports their hypothesis or not. Interestingly, 100% of the children in the play group showed an increase in their score on rule breaking behaviors, significant at a p=<0.05 level. Interestingly, the researchers commented that this significant change “was not clinically meaningful.”(!?)

They characterized a change in IQ data as “marginally significant” for the massage group at p=0.07. Most researchers would simply call anything over p=0.05 not significant.

They only provide part of the data. They do not explain that this checklist involves 8 “syndrome” scores and 3 general scores (total, externalizing and internalizing). So presumably there was no significant difference for 2 of the 3 overall scores, and for the 8 syndrome scores they did not report a significant change in 6, and reported a significant improvement in one and a significant loss in another, which sort of cancelled each other out. Not very impressive.

On the DP-II developmental profile, five areas are assessed: physical, self-help, social, academic, and communication. The massage group showed significant improvements in self-help and communication. The play group showed a significant improvement in social development, while the massage group showed a significant decrease in social development. There were no significant differences in the physical or academic scores. If you add up all the gains and losses on their bar graph (figure 1), it looks like a gain of about 8 points for the massage group compared to a gain of 9 for the play group. It may not be statistically legitimate to draw any conclusions from adding all 5 together, but I’m not sure the inferences the authors draw are legitimate either.

All in all, I don’t find their data very compelling, especially since it is based on subjective caregiver reports and the caregivers were not only not blinded but were present for all the treatment sessions.

Discussion

They interpreted their data to mean that “massage therapy was effective in reducing maladaptive internalizing behaviors in children aged 6 and older” and that “children 2-8 years of age who received massage demonstrated enhanced self-help and communication skills.” They found it “interesting” that children in the massage group remained at the same social developmental level, suggesting that it was because those children had little or no play activity at home. (Did they? We don’t know.)

They were “puzzled” by their failure to find any effect on behaviors in the under-5 age group because they were so sure massage therapy improves children’s moods and anxiety levels. They tried to rationalize what might have gone wrong.

They commented that “anecdotally, the nurses who conducted the massages reported changes in the children over time, including better mood.”

Their whole discussion gave the impression that they believed in massage and were trying to make it look as good as possible given their marginal data.

They recommended massage therapy as a cost-effective option to improve symptoms and functioning in children with untreated HIV.

What Does This Mean?

The whole idea of treating these children with massage in lieu of drugs is abhorrent. These are children who are going to die, children whose lives might be saved with modern medical treatment. Instead of saving their lives, these researchers propose to give them a cheaper treatment (massage) that at best can only hope to produce small short-term improvements. It is demeaning to these children to treat them like second-class citizens and just accept that they will continue to be denied effective treatment. I won’t call it racism, but some might. At the very least it reminds me of Val Jones’ newly coined “shruggies.” Not our problem. Not in our job description. These kids are doomed, but we can tell their parents to massage them. Massage is good.

They observed that AIDS patients treated with antiretroviral drugs show improvements in cognitive and affective symptoms. They speculate that since the drugs improve immune function, they reduce physical symptoms and improve quality of life, thereby attenuating the psychological impairments caused by the disease. Alternative medicine advocates frequently accuse scientific medicine of treating the symptoms instead of the disease. Here’s a case where science addresses the underlying cause (the HIV virus) whereas massage therapy only attempts to address secondary factors (symptoms and possibly immune function). Even if their premise that massage improves immune function is correct, massage is surely not a very effective way to achieve that.

If this study accomplished anything, it was to highlight the plight of these children who are dying and who need not die. It got full ethical approval from the Institutional Review Board, but was it really ethical? Was this study really justified? Was it designed to improve the lives of these children, or were they used as guinea pigs for massage advocates seeking to justify what they believe in and like to do?

This study reminds us that all children need human interaction, play, touch, and TLC. It does nothing to convince me that massage is a useful therapeutic tool beyond the feel-good and human-interaction effects. It certainly does nothing to justify using massage as an alternative to life-saving anti-AIDS drugs.

The money that was spent on this research might have saved lives if it had been spent instead on getting antiretroviral drugs to these unfortunate children. I know it was not a choice between those two options, but I think it must have been very difficult to stand by and see a child get a research-funded massage knowing that you could have spared the money from your own salary to save that child’s life. I wonder if the researchers have nightmares.

REFERENCE:

M. Hernandez-Reif, G. Shor-Posner, J. Baez, S. Soto, R. Mendoza, R. Castillo, N. Quintero, E. Perez, G. Zhang (2006). Dominican Children with HIV not Receiving Antiretrovirals: Massage Therapy Influences their Behavior and Development Evidence-based Complementary and Alternative Medicine, 5 (3), 345-354 DOI: 10.1093/ecam/nem032

Posted in: Clinical Trials, Medical Ethics

Leave a Comment (24) ↓

24 thoughts on “Massage for AIDS

  1. Harriet,

    This is from the relevant journal’s statement on “Ethics” (see: http://www.oxfordjournals.org/our_journals/ecam/for_authors/instauth1.html ):

    “Work offered for publication in the Journal must conform to the standards for experimentation and care set down in the Declaration of Helsinki, Ethical Principles for Medical Research Involving Human Subjects by the World Medical Association ( http://www.wma.net/e/policy/b3.htm ).”

    This is from the Helsinki Declaration:

    “8. Medical research is subject to ethical standards that promote respect for all human beings and protect their health and rights. Some research populations are vulnerable and need special protection. The particular needs of the economically and medically disadvantaged must be recognized.”

    “15. Medical research involving human subjects should be conducted only by scientifically qualified persons and under the supervision of a clinically competent medical person. The responsibility for the human subject must always rest with a medically qualified person and never rest on the subject of the research, even though the subject has given consent.”

    “29. The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic method exists.”

    There’s more, but those are the most pertinent to this “study.”

    The article also states: “Full Institutional Review Board (IRB) approval and ethical approval were obtained for the study from the University of Miami’s School of Medicine.” Hmmm. That IRB is also “the parent IRB” for the TACT (see: http://www.theheart.org/article/907501.do ).

    It would be reasonable to file a complaint with the OHRP, the journal, and its parent company, Oxford Journals.

  2. In terms of questionable ethics, this reminds me of a trial of homeopathy conducted in Honduras on children with infectious diarrhea. However, the homeopathy study was far, far worse.

    Unfortunately, as much as I’d love to be totally down with you and Kim, I appear to be the odd man out here in that I’m not nearly as appalled about this study as I was about the aforementioned study of homeopathy for infectious diarrheal diseases because: (1) the intent of the massage study was clearly not to use massage as any sort of primary treatment for AIDS, but only as an adjunct to help the children not receiving HAART for their HIV infection to feel better; and (2) the homeopathy trial was using a homeopathic (i.e., inactive placebo) treatment to actually treat diarrhea. Children could have died as a result.

    From the introduction of the massage study:

    In the current study, we evaluated massage therapy as an alternative and complementary treatment for enhancing varying behavioral and developmental domains of pre-school Dominican children with HIV infection who were not yet receiving HAART. The impetus for focusing on Dominican children was that no studies have tested the effects of massage on the development of children without HAART living in resource-poor countries.

    And from its conclusion:

    In sum, for untreated children with HIV infection, massage therapy appears to be a viable therapy for promoting greater daily functioning and communication in HIV infected Dominican children and in helping reducing internalizing problems (anxiety, depressed mood, negative thoughts) for Dominican children who have no access to antiretrovirals. Massage therapy may be easily taught to nurses and other health professionals in resource poor countries. Massage therapy may also be administered by a parent or caregiver, making the therapy cost-effective and practical, particularly in resource-strained environments.

    In other words, does massage help behavioral and developmental domains in HIV-positive children who aren’t receiving HAART because they live in a resource-poor region where HAART isn’t available? You can certainly question the validity or importance of the hypothesis (I do as well), the poor quality methodology used (I do as well), and the stretching of the results to a conclusion that is not justified by the data (I do as well), or even the ethics of wasting money on this nonsense (I do as well), but clearly the investigators were not arguing or trying to show that massage is in any way a substitute for HAART. All they were trying to suggest is that it might be useful for HIV-positive children who, for whatever reason, don’t have access to HAART. Yes, you certainly masterfully deconstructed all that was wrong about this study from a methodological standpoint, why its conclusions do not follow from its methods, and the clear bias in the investigators towards massage. However, as much as I hate to say it, I’m afraid you went too far when you said:

    It [the current study] certainly does nothing to justify using massage as an alternative to life-saving anti-AIDS drugs.

    Of course it doesn’t. That was clearly not the intent of the investigators. To imply otherwise, I hate to say, is a straw man argument and weakens your critique. However bad this study is from a scientific and clinical trials point of view (which, again, you showed very clearly), the authors were not trying to justify the use of massage as an alternative to life-saving HAART. I hate to be so blunt, as I have nothing but the utmost respect for you and Kim, but that’s the way I see it.

    The issue of whether the money used for this study could better have been used to purchase HAART is a much more tricky one. For one thing, HAART drugs are very expensive, and this study was likely fairly cheap to do. Indeed, I’m guessing the money used for this study would at best supply HAART for the subjects in the study for a few weeks, not long enough to do any long term good but long enough to do harm in terms of selecting for resistance. Applying those criteria to the homeopathy study I mentioned before, for instance, what was spent on the study could almost certainly have bought lots and lots of Pedialyte. Moreover, one should be very careful about applying the classic “the money could have been spent better” argument, as it could apply to a fair number of trials of “conventional” medicine as well.

  3. BenAlbert says:

    Hi, I don’t disagree with your critique of the study at all, but tend to agree with Dr Gorski, that it doesn’t sound like they really were advocating massage instead of antiretrovirals if they were available. But he has said that better than I can. My beef is with this.

    “I think it must have been very difficult to stand by and see a child get a research-funded massage knowing that you could have spared the money from your own salary to save that child’s life. I wonder if the researchers have nightmares.”

    I think this quote is a bit unfair really. Any healthworker in the 3rd world (and often in the 1st) comes across situations where a patient would do better with a treatment that they can afford. But, I don’t think it is fair to criticise the health professional for not shelling out from their own pocket.

    From my own experience I spent 3 months volunteering as a doctor at a mission hospital in Kenya (as a final year med student). I saw hundreds of people with HIV, many of them couldn’t afford treatment. It would have been possible for me to afford a years treatment for one of them if I broke into my savings. But who should I give it to? Should I borrow money to fund two? Perhaps the massage advocates were not being quite so generous with their time, but equally they may have felt that they were genuinely (though misguidedly) trying to find a way to improve these kids lives. Either way, even if they were selfishly there entirely to further their own agenda I don’t think that charity can simply be expected.

    I don’t have nightmares about the people whose drugs I didn’t buy, though I remember the feelings the situation brought up. Do you really think I should have nightmares?

    -Dr Ben

  4. Dave,

    I beg to differ. The ethical statements are clear, and do not allow a distinction between rich and poor subjects or between research done in third world countries and that done in “developed” countries. The language in Helsinki paragraph #8 was put there for exactly that reason. Perhaps I should have added paragraph 29, which states:

    “The physician may combine medical research with medical care, only to the extent that the research is justified by its potential prophylactic, diagnostic or therapeutic value. When medical research is combined with medical care, additional standards apply to protect the patients who are research subjects.”

    The point of all this, and it goes back to Claude Bernard, is that there is an ethical mandate for biomedical researchers to violate the Prime Directive, if doing so is medically advantageous to experimental subjects. In other, less flippant words, medically knowledgeable researchers may not engage seriously ill human subjects for a trial and then stand by knowing that those subjects are not receiving a proven treatment. Remember Tuskegee? Price of the proven treatment, location, and the goals of the trial are irrelevant.

    This isn’t the first time this kind of thing has reared its ugly head in recent years:

    http://content.nejm.org/cgi/content/full/337/12/847?ijkey=c20ab0ee4db9f9cdf976796ed8a17b0b84bb6ccd&keytype2=tf_ipsecsha

    Admittedly, some reasonable people disagree in some cases:

    http://content.nejm.org/cgi/content/full/342/13/967

    What, then, should these authors have done? They should have spent their time and resources working for obtaining ongoing, rational treatments for those children. They should have scrapped their study until they could do that, because otherwise it would have been, and was, unethical. The IRB should have told them as much during its evaluation of their protocol.

  5. Harriet Hall says:

    When I said the study does nothing to justify using massage as an alternative to AIDS treatment, my intent was to be facetious. I guess that didn’t come across. I probably should have appended a smiley face. I thought it was abundantly clear that they were not even considering the alternative of effective anti-AIDS treatment for these kids and I thought I had made it clear that that was what had disturbed me about the study in the first place.

    As for money, I said I realized it was not a choice between doing massage research and purchasing AIDS meds. I was talking about how difficult it must have been for a humane researcher to confront these doomed children personally, knowing how inexpensively their lives could be saved and how poorly conceived this research study really was.

    And I think a lot of “conventional” trials should never have been done either. The question of how much good the research money can do is sometimes subordinated to questions like what will persuade a funding agency, what will further a researcher’s career, and what might sell more pharmaceuticals.

  6. Harriet Hall says:

    BenAlbert’s comments remind me of why medical missionary and charity efforts make me uncomfortable. I’ve experienced this first-hand with Flying Doctors in Baja. We go into a poor country, help a few individuals temporarily, and it makes us feel virtuous, but it does nothing to solve the real problem. In fact, I wonder if the local governments are just that less likely to do something effective because they know rich foreigners are willing to help.

    Muhammed Yunas had a better idea. Micro-loans effectively attack the “disease” of poverty instead of putting a Bandaid on a symptomatic lesion.
    http://www.thirdworldtraveler.com/Heroes/Muhammed_Yunas.html

    It’s the old argument about give a man a fish, feed him for a day; teach him how to fish, feed him for a lifetime. We probably “shouldn’t” be throwing anti-AIDS drugs at these countries but we “should” be helping them figure out the best way to help themselves out of poverty. The beauty of Yunas’ approach is that he respects people’s dignity and leaves them responsible for their own lives by lending money rather than giving, and he organizes the borrowers into small groups that support each other and work to improve their quality of life in many other ways, like getting education for their children.

    I don’t mean to imply that those 3 months in Kenya were not well worthwhile. I just wonder whether the money spent on airfare and expenses might have done even more good in the long run if it had been invested in people’s futures as loans a la Yunas.

  7. Karl Withakay says:

    How much should one be concerned with the potential “misuse” of trial results?

    Let’s say for the sake of argument that ethical concerns aside, this was an otherwise high quality, well executed trial, that showed massage was a moderately effective but inferior treatment for AIDS in a population group. Should one be concerned that it could lead to various health organizations or insurance companies across the world making an actuarial decision that massage was an economically more attractive treatment option for those who can’t afford to pay for HAART themselves than diverting charity/insurance/government funds to supplying those people with HARRT?

    If you are researching a treatment for which you believe if it is effective at all, it will be significantly inferior to established treatment, but also less expensive, is it ethically or morally acceptable to investigate that treatment on the justification that not everyone can afford the established, effective treatment?

    If so, where do you draw the line?

  8. David Gorski says:

    I beg to differ. The ethical statements are clear, and do not allow a distinction between rich and poor subjects or between research done in third world countries and that done in “developed” countries.

    I never said or implied that they should be. All I argued is that this study is not as appalling as the homeopathy study. And it’s not. At the very worst, all you can say is that it does no harm and maybe even helps, at least in terms of feeling good to the children. You can also say it was a waste of resources.

    I’m also afraid your analogy to Tuskegee is a tad overblown. In the Tuskegee experiment, subjects were intentionally denied known effective therapy for syphilis in order to examine the natural history of the disease. Denying therapy was inherent in the trial design, and observing the natural history of the disease was the primary endpoint. Even so, at the time the trial was started it was not quite as unethical as it now sounds today. It was bad, but not the horror that it’s now known as. The reason is that there was no good therapy for syphilis at the time; so observing untreated syphilis was arguably no worse than the treatments available at the time. What made this trial horrific and unethical is that, even after effective therapy for syphilis became available (penicillin), the study continued for decades and its subjects were continued to be denied that effective treatment. Worse, it was only publicity that finally stopped the trial, not a sudden realization by researchers that, gee, we could treat these men with antibiotics. Unless you can show that the investigators here would have denied these children HAART in favor of massage if HAART became available to them, I find the analogy only tangential, at best, although it does raise an interesting question of where to draw the line.

    As for whether research standards should vary depending on the standard of care available where a study is being done, you make a reasonable argument that they shouldn’t and that the study should never have been undertaken in the first place. However, I think reasonable people can disagree over whether this is as rigid as you make it sound. For example, imagine a treatment that, it is hoped, would greatly alleviate suffering from a disease in a Third World country as medicine is practiced there. Doing a study in which the U.S. standard of care is applied to subjects during a clinical trial of the drug might not be sufficiently informative as to whether the treatment would work under the conditions under which it will be utilized. What does an ethical researcher do in such a situation? Do a trial that might not give a useful result for the “real world” conditions “on the ground” or do the standard of care and accept that the result might not be as applicable as one would wish?

    Although it often is, the application of the above principle is not always as black and white as you make it sound, as even the editorials to which you link concede. In fact, even in the case of missionary and humanitarian work with no research intent the ethical quandaries are legion, as Harriet and BenAlbert make clear.

  9. Oh boy. Let’s get one thing out of the way right now: medical practice ethics are different from human studies ethics. My way of thinking of it in the case of humanitarian work is that the physician is doing the patient a favor. In the case of human trials, no matter what the scenario, it is the human subject who is doing the investigator a favor. Thus, in the latter case, there is a much higher standard of protection than in the former. This is recognized in ethical treatises, such as the “additional standards apply to protect the patients who are research subjects” language quoted above from Helsinki, and these passages from the Belmont Report, created mainly because of Tuskegee:

    “Research and practice may be carried on together when research is designed to evaluate the safety and efficacy of a therapy. This need not cause any confusion regarding whether or not the activity requires review; the general rule is that if there is any element of research in an activity, that activity should undergo review for the protection of human subjects.”

    “2. Beneficence. — Persons are treated in an ethical manner not only by respecting their decisions and protecting them from harm, but also by making efforts to secure their well-being. Such treatment falls under the principle of beneficence. The term “beneficence” is often understood to cover acts of kindness or charity that go beyond strict obligation. In this document, beneficence is understood in a stronger sense, as an obligation. Two general rules have been formulated as complementary expressions of beneficent actions in this sense: (1) do not harm and (2) maximize possible benefits and minimize possible harms.”

    “…it can be seen how conceptions of justice are relevant to research involving human subjects. For example, the selection of research subjects needs to be scrutinized in order to determine whether some classes (e.g., welfare patients, particular racial and ethnic minorities, or persons confined to institutions) are being systematically selected simply because of their easy availability, their compromised position, or their manipulability, rather than for reasons directly related to the problem being studied. Finally, whenever research supported by public funds leads to the development of therapeutic devices and procedures, justice demands both that these not provide advantages only to those who can afford them and that such research should not unduly involve persons from groups unlikely to be among the beneficiaries of subsequent applications of the research.”

    Next: You and I might interpret Tuskegee as having involved the deliberate withholding of a proven treatment, but the researchers and their apologists did not:

    “…the lack of treatment was not contrived by the USPHS but was an established fact of which they proposed to take advantage.”–Dr. Charles W. Barnett, quoted in “Debate revives on the PHS syphilis study,” Medical World News (April 19, 1974), p. 37.

    The only difference between that and this, it seems, is the price of the treatment.

    Sure it isn’t always black and white, but the starting point for thinking about such issues should default to “beneficence [being] understood in a stronger sense, as an obligation.” There had better be damn good reasons for deviating from that, and in this case there were not.

  10. David Gorski says:

    I’m very familiar with clinical trial ethics, the Belmont Report, the Common Rule, the Helsinki Declaration, etc., etc., and am quite aware that clinical trial ethics are different than ethics of medical care. After all, I’m a translational researcher. I do basic research, but I also write and run clinical trials and have to get them through our IRB. You can complain to the IRB that approved this study and OHRP and it might even be worthwhile to do so, but I can tell you that it’s pretty unlikely they will see things the same way you do. (Obviously complaining to the journal would be a waste of time, given that it’s a CAM journal.) Whether they should is a separate question. In any case, the homeopathy study was obviously unethical; to me at least, that’s not as obviously the case for the study Harriet discussed. I can see how the massage study might have gotten through an IRB relatively unscathed; I fail to see how the homeopathy study ever could, unless the IRB that reviewed it was completely ignorant of what homeopathy is.

    But let me play Devil’s advocate here for a second. Perhaps a useful exercise would be to boil it down to your starting point, which no one (at least no one that I’m aware of) would be likely to disagree with, and then ask the question: How, specifically, in the case of the massage study was the principle of beneficence violated, even understanding beneficence in its stronger sense, as a sense of obligation? Specifically, what potential harms were not minimized? How were benefits not maximized? You’re quite correct that there had better be a “damned good” reason for deviating from beneficence. I would even add to your statement that that is particularly true in the case of studies for which children are the subjects. What you’re less clear about is exactly how this study deviated from that principle. Remember, the researchers were not claiming that massage would treat HIV, only that it might “enhance varying behavioral and developmental domains.” I’m not entirely disagreeing with you, but I’m not entirely agreeing with you either. You haven’t entirely convinced me where the harm to human subjects is in this particular trial lies or how the principle of beneficence has been so egregiously violated. Some specifics would be nice.

    That this trial was bad science, you don’t have to convince me of, of course. However, there are plenty of trials of “conventional” therapy that are dubious science out there. Do they automatically violate the principle of beneficence as well? Does any trial testing a merely questionable or highly debatable hypothesis violate the principle of beneficence? What about trials testing a hypothesis that is just very controversial? Where should the line be drawn?

    BTW, you shouldn’t get in debates with me when I happen to be in my office all day writing, especially not on days when I drive in with my wife to work and she’s working a 12 hour shift. I look for any excuse for a break from the drudgery of a grant. I suppose I could go engage Dana Ullman in the other comment thread, but, really, this is far more intellectually stimulating. Dealing with Dana, I fear, forces my neurons to activate NF-kappaB and other cell survival pathways in order to fight off a wave of neuron-apoptosing pseudoscientific nonsense.;-)

  11. Dave,

    Benefits were not maximized because HIV was not treated. Part of the reason for the passages quoted above is to discourage investigators from ducking that obligation in exactly the way that these ones did: by claiming, in your words, that they “were not trying to justify the use of massage as an alternative to life-saving HAART.” But they really were doing that, as Karl W. suggested. They didn’t just choose any kids; they chose kids who were HIV+, looked at behaviors and symptoms that they attributed to that infection, and looked for changes in those behaviors and symptoms as outcomes. In Harriet’s words,

    “They seemed to make two main claims for massage: enhancement of immune function and psychological/developmental effects. This study was not designed to assess immune function, but it suggested that improved immune function would improve psychological/developmental outcomes; in fact, it speculated about possible mechanisms for this.

    “They stated as a fact that massage improves immune function;…”

    And later:

    “They recommended massage therapy as a cost-effective option to improve symptoms and functioning in children with untreated HIV.”

    “They observed that AIDS patients treated with antiretroviral drugs show improvements in cognitive and affective symptoms. They speculate that since the drugs improve immune function, they reduce physical symptoms and improve quality of life, thereby attenuating the psychological impairments caused by the disease.”

    Thus it seems that the authors were looking for (speculative) outcomes from massage that they conceded had already been shown to be (real) outcomes of anti-retroviral therapy: “improvements in cognitive and affective symptoms.” Just because they didn’t claim that massage would be life-saving doesn’t mean that they weren’t looking at it as an alternative to HAART. Of course they were; that’s why they went down there.

  12. BenAlbert says:

    Wow, the Yunas bank certainly seems like a worthwhile concept. Food for thought.

    Certainly my time in Kenya was not completely selfless. I chose it for the personal experience, the ‘feeling of virtue’, the interesting medical cases and cultural experience. Maybe the money in my air fares could have done more good.

    But while I was there and gone, I was replaced by further students when I left, so benefit to the local community of the first world Medical ‘Outreach’ is ongoing. Further, I was able to educate the native doctors at the hospital in some areas – potentially improving their ongoing care and the health of the community. In some cases I could provide useful health education to the patients as well. Lastly health is so important in the 3rd world, if you are to have any chance of getting out of poverty. Once you are too sick to work you have no chance or are a burden to your family who may suffer to support you. Short term injections in health aid could therefore help people in the community long term by reducing disability from poorly treated problems or chronic infections, that can be treated.

    Anyway I take your point, and share your reservations with many third world charity schemes.

  13. Harriet Hall says:

    Your point about health coming first is well taken.

    Bjorn Lomborg, the “Skeptical Environmentalist,” has written several books as part of an ongoing effort to determine how we can best allot our limited funds to improve global human welfare. He edited the findings of the Copenhagen Consensus: the raters put 3 health measures in their top 4: reducing the spread of AIDS, providing micronutrients to malnourished children, and controlling malaria with bed netting. They felt these would provide the biggest bang for the buck. Bill Gates apparently believed them: he is investing huge amounts of money in these areas.

    Incidentally, trade liberalization was number 3, and the Kyoto agreement was was at the bottom of the list. More at http://en.wikipedia.org/wiki/Copenhagen_Consensus#Ratings
    It’s all very controversial, but certainly stimulates thought.

    Lomborg was demonized for his ideas by people who had not even read what he wrote. He was accused of scientific dishonesty but exonerated. His enemies labelled him as an anti-environmentalist when he was really a thoughtful environmentalist who urged caution so we don’t rush into poorly thought out actions that do more harm than good. Like corn for biofuel. :-)

  14. BenAlbert says:

    I enjoyed the Bjorn Longberg ‘Skeptical Environmentalist’ alot. Plenty of food for thought there, I was most disconcerted by the apparent futility of the Kyoto protocol. And most found disagreement with his discussion of biodiversity. I might try and pick up one of his more recent books

  15. David Gorski says:

    Kimball,

    You almost have me. I had actually forgotten about the part of the Helsinki Declaration that changed the wording from “best local” to “best” therapies. I understand why that was done, but I see a problem with it that could have some fairly negative consequences too. That’s why I remain a bit skeptical that it was unabashedly in the best interest of potential research subjects and, indeed, the denizens of Third World nations. Whether the negatives equal the positives of putting the word “best” in, I don’t know. I do know an old surgical saying that the enemy of “good” is “better” or “best.” It means that trying to go forward to do “better” during an operation (for example, wanting to make that anastomosis “just a little bit better”) is often how surgeons get into trouble and cause complications, such as putting a hole in a large blood vessel while trying to put “just one more” stitch into a structure that was adequately stitched already.

    I may not be in the majority here, but when I look at the concept of beneficence I tend to take a wider view. In other words, is a research subject likely to be better off for having been in a trial than by not having been in a trial, and will the results of the trial, whether negative or positive, benefit the society in which the trial is conducted. Insisting on only utilizing the “best” therapy rather than the “best local” is likely to guarantee that a lot of trials that might benefit the impoverished don’t get done. For example, does it benefit patients to have HAART for a few weeks or months of such a trial and then to have it no longer? AIDS might be staved off for a few months, but at the cost of perhaps inducing resistance that might make future treatment more difficult, if HAART were to become available. Because under the newer Declaration, trials of second-tier treatments or even of adjunctive “complementary” therapies designed to make people feel better when HIV can’t be treated due to resource constraints are a priori considered automatically unethical. End of story. So the actual effect is that no trials of this sort, even for potentially effective “lesser treatments” are done that might benefit patients for whom HAART is not available. Better trumps good.

    I consider that a bit more dogmatic than I’m entirely comfortable with. Things are not so black and white. You are probably right that this trial, at least under the Helsinki Declaration, is probably unethical. Outside of the Helsinki Declaration, however, as a matter of conscience, I’m not nearly as sure this trial is as bad as you paint it. Look at the Belmont Report and its discussion of beneficence, for example, which states:

    The principle of beneficence often occupies a well-defined justifying role in many areas of research involving human subjects. An example is found in research involving children. Effective ways of treating childhood diseases and fostering healthy development are benefits that serve to justify research involving children – - even when individual research subjects are not direct beneficiaries. Research also makes is possible to avoid the harm that may result from the application of previously accepted routine practices that on closer investigation turn out to be dangerous. But the role of the principle of beneficence is not always so unambiguous. A difficult ethical problem remains, for example, about research that presents more than minimal risk without immediate prospect of direct benefit to the children involved. Some have argued that such research is inadmissible, while others have pointed out that this limit would rule out much research promising great benefit to children in the future. Here again, as with all hard cases, the different claims covered by the principle of beneficence may come into conflict and force difficult choices.

    It’s a general principle in clinical trial ethics that more latitude is allowed when a clinical trial has minimal (or zero) risk; so let’s consider a proposed treatment that is minimal or no risk and is known to have other benefits (just not the ones the investigators think it has). Yes, massage therapy. Are the children better off for having been in the study and gotten either massage or play therapy, even though they didn’t get HAART? Maybe, maybe not. Are they worse off? Very likely not. After all, they wouldn’t have gotten HAART anyway. It’s hard to make an argument that the trial kept them from getting other, non-HAART therapy that might have helped them with their developmental and cognitive complications, because they weren’t getting them either. Again, contrast to the homeopathy study, where it is clear that the babies in the study were not better off for having participated. For the massage study, an argument can certainly be made that no harm was done, and that the participants may have had a mild benefit–again, just not the benefit postulated by the investigators. So, although I concede that under the Helsinki Declaration this study was probably unethical because the children did not get state-of-the-art HAART therapy (not to mention that the scientific premise was dubious), after thinking about it, I’ve come to question whether the Helsinki standard is always in the best interests of potential research subjects. More often than not, it likely is, but there are lots of exceptions I can think of where it may not be. Better trumps good again, and absolutist thinking prevails.

  16. David Gorski says:

    Lomborg was demonized for his ideas by people who had not even read what he wrote. He was accused of scientific dishonesty but exonerated. His enemies labelled him as an anti-environmentalist when he was really a thoughtful environmentalist who urged caution so we don’t rush into poorly thought out actions that do more harm than good. Like corn for biofuel.

    Actually, Harriet, Lomborg is demonized because he uses a lot of crank arguments to make his case and flirts with being an anthropogenic global warming denialist. His line seems to be, “Well, yes, AGW is happening, but don’t worry, be happy; it’s not bad.” That he may have been correct about corn for biofuel doesn’t change the totality of why overall he’s off base. After all, Michael Fumento and Steve Milloy, despite being cranks and industry shills for virtually everything else, are correct that antivaccine activists support fear-mongering based on pseudoscience.

    A sampling of explanations of why Lomborg is so off base (some are short posts with a lot of links):

    http://www.lomborg-errors.dk/
    http://scienceblogs.com/pharyngula/2007/08/dont_look_to_bjrn_lomborg_thou.php
    http://www.dailyhowler.com/dh032207.shtml
    http://www.desmogblog.com/global-warming-and-the-posture-of-skepticism-bjorn-lomborg
    http://scienceblogs.com/islandofdoubt/2007/03/what_to_do_with_bjorn_lomborg_1.php
    http://scienceblogs.com/deltoid/2008/08/so_whats_wrong_with_lomborg.php
    http://www.salon.com/books/review/2007/08/29/cool_it/index.html
    http://scienceblogs.com/islandofdoubt/2007/08/hes_back_and_bjorn_lomborg_sti.php
    http://scienceblogs.com/islandofdoubt/2007/10/inside_bjorn_lomborgs_brain.php
    http://scienceblogs.com/intersection/2007/09/taking_on_lomborg_on_desmogblo.php
    http://scienceblogs.com/deltoid/2007/02/misinformation_from_lomborg.php
    http://scienceblogs.com/deltoid/2006/11/lomborg_spreads_ddt_ban_myth.php

    IMHO, Lomborg richly deserves the castigation he receives, and I was one of the people who was appalled to see him published in The Skeptical Inquirer. (Come to think of it, certain skeptical magazines have been publishing more crankery; for example, Skeptic published an anti-animal research screed full of misinformation and crank arguments.) Indeed, the reason he ranks global warming so low is because he misrepresents the science of what is happening. Of course, he sounds reasonable, which is why he’s able to convince a lot of people that he’s taking a reasonable “middle course,” when he’s not.

  17. qetzal says:

    I agree with Dr. Gorski’s concerns.

    From what’s been presented here, I agree this trial was unethical. It had a bogus rationale and a flawed design that practically eliminated any chance to obtain useful information from the study. That alone makes it unethical.

    But I do think there is a problem with insisting that any interventional study must provide the current best available treatment to all patient-subjects. If that were so, we could only conduct trials on adjunct treatments and treatments for otherwise untreatable conditions. We could never test a new, potentially better first line treatment in place of an existing but suboptimal treatment.

    I also think it’s a mistake to absolutely reject trials of treatments that may only benefit patients who don’t have access to the best available treatment (e.g. for economic reasons). Such trials deserve much greater scrutiny, because they certainly entail difficult ethical judgements and are probably at greater risk of ethical abuse, but I don’t agree that they are prima facia unethical.

    One solution could be to require all protocols to clearly show that all patients will receive the best current therapy, or to clearly state that they will not and to provide abundant and compelling justification for that. Protocols in the latter category could be required to pass a second tier of ethical and scientific review.

  18. Harriet Hall says:

    “[Lomborg's] line seems to be, “Well, yes, AGW is happening, but don’t worry, be happy; it’s not bad.”

    I’ve read his books, and I think I can claim to have a reasonable degree of reading comprehension, and that was not at all what I read in his books. I think people are reading him with such strong preconceptions and emotions that they are not understanding his message. I don’t think he ranks global warming low as a threat; what he ranks low is plans like Kyoto, which even many advocates agree is far from ideal.

    I certainly don’t agree with everything he says. He’s far from being an expert in the fields he discusses, so of course he makes mistakes. He approaches the problem from a cost-benefit perspective, which is only one of many ways we should look at it.

    The message I get from Lomborg is that if we panic and throw money enthusiastically at every promising proposal to reduce global warming, we may (1) not actually achieve as much as we could to reach that goal and (2) lose the chance to use some of that money to benefit humans in many other areas. His approach reminds me of one of the tongue-in-cheek rules for interns in the novel “The House of God” – the first thing to do in case of a cardiac arrest is to stop and take your own pulse.

    Lomborg asks us to carefully think through all the consequences. Every dollar spent on one program is a dollar less available for another program. Something that superficially looks good, like organic food, might have unintended consequences like using up more land and raising the price of food for the poor; and maybe all organic food is not really healthier. It would probably be a mistake to spend money to convert all farms to organic tomorrow. It would probably be a better idea to invest money in research to figure out the best ways to provide healthy, affordable food to everyone with minimal impact on the environment. Once we know more, then it will be time to act.

    He’s not telling us “what” to do about global warming or about any of the other problems facing humanity. He’s telling us “how” to think more carefully about what to do. And he recommends constant evaluation and re-assessment of programs so we can scrap them if they’re not working.

    The message I got from his books was that we should “Cool It” (the title of his last book) – that we should try to cool the overheated earth but also cool the heated emotions, avoid knee-jerk reactions, and use the best science and critical thinking skills we can muster to solve the world’s problems rationally.

  19. David Gorski says:

    Unfortunately, to make his case, Lomborg frequently makes gross misrepresentations of the state of climate science, as is well just flat out wrong statements, as documented in the numerous links I provided, as well as these:

    http://climateprogress.org/2007/09/12/debating-bjorn-lomborg-global-warming-denier/
    http://climateprogress.org/2007/10/09/bjorn-lomborg-greenland-glacier-sea-level-rise/
    http://climateprogress.org/2007/09/13/debunking-bjorn-lomborg-cool-it-polar-bears/
    http://climateprogress.org/2007/09/14/debunking-bjorn-lomborg-cool-it-sea-level-rise/
    http://climateprogress.org/2007/09/17/debunking-bjorn-lomborg-cool-it-water-heat-waves-global-warming/
    http://www.lomborg-errors.dk/methods.htm

    That’s hardly using “the best science,” nor is it a ringing endorsement that Lomborg is in any position to advise us “how to think” about these issues. How to think about any scientific issue, even if one comes at it from an economic perspective, depends on understanding and accurately representing what the issues are, and Lomborg clearly fails at this. Indeed, here‘s what scientists (including economists) say about The Skeptical Environmentalist. They read the book, just as you did. Of course, if I hadn’t taken a lot of time to school myself on AGW over the last year or two, I wouldn’t have recognized a lot of Lomborg’s misrepresentations in, for example, his Skeptical Inquirer article either. He’s very clever at sounding reasonable and cloaking his arguments in concern for developing worlds. Occasionally he even makes sense.

    It’s more than just mistakes, though, even though there are a lot of them, that make his research and understanding of the issues quite suspect. If it were only mistakes, there wouldn’t be such an obvious pattern to his mistakes. No his “mistakes” are all in one direction. He also parrots common AGW denialist canards, for instance, straw men about what the 2007 UN report on AGW said about the potential rise in sea level if the Greenland and Antarctic ice shelves fall into the sea. Although I haven’t read his books, I’ve read a lot of his articles. Indeed, his article in The Skeptical Inquirer was a perfect example and contained several examples of the arguments refuted in the links I provided.

    So, sure, Lomborg makes “mistakes.” The problem is, at least for me, that they’re too numerous and all in the same direction to consider him anything other than an ideologue and hack. I don’t mean to “gore” any oxen (sorry, couldn’t resist), but if Lomborg can’t even be bothered to get his basic facts and science right about the problem of the environment and global climate change, I really do have a hard time taking anything he says about “how to think” about them seriously. The more I learn about Lomborg and his errors, the less convincing I find him.

  20. @qetzal:

    Sorry, I was trying to address this particular study and thus probably oversimplified. Human studies ethics don’t require that “any interventional study must provide the current best available treatment to ALL patient-subjects.” They require that “The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods.” (Helsinki paragraph 29). In other words, the control group may not receive “placebo” or no treatment, but must receive the best current treatment, assuming there is one. There are exceptions in cases of trivial diseases, or conditions in which short term withholding of effective interventions is not risky, and maybe some others.

    What’s not explicitly stated in that passage, but is nevertheless a fairly ironclad ethical precept, is that depriving the experimental group of the best current treatment is only acceptable if there is good a priori reason to believe that the experimental treatment is at least as good as the current standard. “Clinical equipoise” describes the state of “genuine uncertainty in the expert medical community” over whether the new treatment is better or worse than the current one, and many have held that this must be the case in order for such a controlled trial to be ethical. (there is some controversy about this, but it’s not really relevant here).

    That’s why the usual order of investigations (if possible) of a proposed treatment proceeds from hypothesis (based on science!) to bench to animal to small human trials to larger human trials, with each step contingent upon the previous one having shown promise (and why, by the way, many “CAM” trials that bypass that scheme, justified by “popularity,” are unethical). Without that process, it is usually not possible to assign even a qualitative prior probability with any confidence.

    Getting back to the study under consideration here, since the prior probability of massage being comparable to antiretroviral therapy for HIV infection is zero, it would not do to give HAART only to the control group; it must be given to all the subjects. Then, if someone wants to randomize half to receive massage, based on some rational hypothesis, fine.

    I think that David and I are now in essential agreement. It’s not black and white, and better sometimes is the enemy of good. I don’t think this study is that, however, and I’m not sure we’ve seen one yet.

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