Comments on: Sick Girl

Sick Girl

homunculus — Mon, 07 Jan 2008 13:05:20 -0800

Trial by Transplant. "Most transplant recipients are grateful beyond measure. Amy Silverstein's view, after nearly two decades with a donated heart, is more conflicted and often bleak. Much of her life, as described in Sick Girl, has revolved around nauseating drugs, ongoing fatigue, painful tests, ER visits and hospitalizations without end—and the constant fear that the next heartbeat could be her last. At low ebb, she has teetered on the edge of giving up."

By: astruc

astruc — Mon, 07 Jan 2008 13:28:09 -0800

Ugh, I know how she feels. I had open heart surgery at Columbia Presbyterian as well. I was sick for five years leading up to the surgery, and have never really felt like I recovered, using that term loosely. I don't even know what recovery means anymore. And I'm tired of being a good soldier and bucking up for my family's sake. I once told them that there are fates worse than death, but they are too healthy to understand. When my mom got cancer and was put through the tortures, she apologized to me for minimizing my own illnesses over the years.

By: Mental Wimp

Mental Wimp — Mon, 07 Jan 2008 13:32:00 -0800

The value of organ transplantation is, by and large, unproven and its use driven mostly by anecdote and observation, not rigorous trials of benefits and risks. Huge amounts of money are spent on hope and little regard is given to the downsides. Unfortunately, this characterizes a great deal of "big medicine" and drives of the cost of health care in the US without necessarily benefiting anyones health.

By: tommasz

tommasz — Mon, 07 Jan 2008 13:40:17 -0800

I had always wondered how they handled the nerves in a heart transplant, now I know. I suppose the immune system wouldn't allow them to work, even if they tried to attach them. It's amazing that it works at all, I suppose, but shouldn't our criteria for success be higher when it comes to human lives?

By: thehmsbeagle

thehmsbeagle — Mon, 07 Jan 2008 13:51:11 -0800

This is a really good post. I just had my entire perception of how transplants work reset. Thanks.

By: homunculus

homunculus — Mon, 07 Jan 2008 13:52:38 -0800

Looking for the heart of cell matters

By: schroedinger

schroedinger — Mon, 07 Jan 2008 13:55:11 -0800

The past year was tough for me for a number of reasons, including my health. A few medium-sized events, a few nagging illnesses that took forever to beat, and a lot of little crap things, all piling up and snowballing. Nothing was even close to what someone who has cancer or another serious chronic illness or is on immunno-suppressive therapy goes through. I consider myself a pretty strong person, yet by the end of the year I was feeling horrifically beat down and teetering on the edge of major depression. I can't even imagine what it would be like to have a year a thousand times worse than mine, year after year after year. I honestly don't think I could last that long. Mental Wimp, is that true? I'm honestly asking--that's shocking if it is. No long-term studies? Nothing?

By: small_ruminant

small_ruminant — Mon, 07 Jan 2008 13:59:26 -0800

Gah. I can't even finish that article. When I see the amount of pain and suffering so many people go through in the name of being cured I don't think I'd have it in me. But then I'm a wimp on so many levels. In my experience, kidney transplants are different- they're miracle cures, though perhaps they only seem that way when compared to the hell that is dialysis.

By: agregoli

agregoli — Mon, 07 Jan 2008 14:05:20 -0800

Great post, thank you.

By: cmgonzalez

cmgonzalez — Mon, 07 Jan 2008 14:17:59 -0800

That was a tough read. There was a piece on her a little while back in Marie Claire, possibly around the time the book came out.

By: NucleophilicAttack

NucleophilicAttack — Mon, 07 Jan 2008 14:21:57 -0800

I will be blunt: Mental Wimp has no idea what he's talking about. Just to give one (of a countless number of examples):

It has been suspected for years that transplantation resulted in better survival than did dialysis. But randomized trials comparing survival during dialysis treatment and after transplantation are neither feasible nor ethical, and there is a well-recognized problem of selection bias. As now documented by Wolfe et al., the mortality rate of patients on dialysis who are placed on a waiting list for transplantation and who continue to receive dialysis is only half that of patients who are not put on a waiting list. A few early small studies compared the survival of patients with end-stage renal disease on dialysis with survival after transplantation and found no difference after correction for initial coexisting conditions.4 It required the establishment of large registries for this issue to be addressed in a definitive way. In 1993, Port et al.5 used statewide data from the Michigan Kidney Registry to show, in a population-based analysis, that transplantation conferred a substantial survival advantage among patients on the waiting list. Now, by merging data from the U.S. Renal Data System with information about the renal-transplantation waiting list from the Transplant Scientific Registry operated by the United Network for Organ Sharing, Wolfe et al. have provided a convincing answer to this most basic question about therapy for patients with end-stage renal disease. A simple search on pubmed with the limits of "human" & "clinical trials" and the keyword "transplantation," turns up 17,079 papers on the topic. The fact is, rigorous, ethical, and yet quantitative studies demonstrating the benefits of lung, bone marrow and kidney among many other organs abound in the literature.

By: Mental Wimp

Mental Wimp — Mon, 07 Jan 2008 14:35:51 -0800

...is that true? Well, some time ago someone told me this, and I couldn't believe it either, so I did a little investigating. I still can't find any randomized trials in Medline, but I'd be interested if anyone knows of one. Yes, there have been long-term observational studies, but they are hopelessly biased because only the "healthiest" patients are selected for the surgeries. A few meta-analyses have been done attempting to control for such biases, but with mixed results. Even quality of life studies have been equivocal on balance. Surgical procedures don't need anyones approval to be done. Basically, if a surgeon decides to do something, it can be done. For drugs and devices, FDA requires some minimal demonstration of efficacy (although there are problems here as well). You'll see transplants defended as "obviously" effective and absolute certainty about the efficacy from people who directly benefit economically from the procedures. And many patient swear that their quality of life is better, but, as this article points out, not all is rosy in their world, even when compared to pretransplant life. The lack of direct demonstration of efficacy extends to things like coronary by-pass surgery and coronary angioplasty as well. Again meta-analyses have been done, but with little evidence of clear benefit compared to medical management. This is a dirty little secret about our health care system and what it pays for. Like I said, if someone else has additional information not available on Medline, I would like to be enlightened.

By: longdaysjourney

longdaysjourney — Mon, 07 Jan 2008 14:41:27 -0800

Everyone who opposes stem-cell research should have to read this. (Not that it would change their minds, probably, but hopefully some of them would have the decency to feel a bit guilty.)

By: Mental Wimp

Mental Wimp — Mon, 07 Jan 2008 14:42:46 -0800

NucleophilicAttack Yes, there are many "randomized trials" but if you look at them they are comparing one anti-rejection medication to another, or one prophylaxis to another, not comparing transplant to medical management. And the three you linked to are not randomized trials, but observational studies attempting to control (inadequately) for the large biases in selecting patients for transplant. The very sickest patients are not selected and they contribute heavily to the high mortality rate. I know the limitations of these methods (e.g., proportional hazards or "Cox" regression), and they require assumptions generally not testable in the data. That said, I was referring to organ, not tissue transplantation. For some, though not all, diseases for which marrow or stem cells are transplanted, randomized trials have been done. Unfortunately, enthusiasm for this treatment has led to some disasters. For example, marrow transplants for breast cancer were done for some time before a randomized trial proved they were killing patients prematurely. It just such stories that cause me skepticism when rigorous studies aren't done prior to widely disseminating potentially dangerous treatments like this. By the way, the same story exists for back surgeries addressing pain.

By: miss tea

miss tea — Mon, 07 Jan 2008 14:52:52 -0800

I thought Amy's story was very moving. There are always trade-offs to any medical procedure, especially the most invasive (transplant, chemotherapy, radiation). My mother has cancer, and I know from many with the same disease that radiation, especially, can cause horrible long-term side-effects. Mostly, I appreciated Amy's honesty about her life. As I have posted here before, one of the things I've found to be terribly pernicious about the cancer "world" (since that is what I am familiar with) is the all-or-nothing, you're a fighter or you're not, kind of mentality. It seems the transplant "world" is similar. Amy is clearly a fighter, and I find it hard to believe anyone would begrudge her speaking the truth about the many terrible experiences that go along with being a transplant recipient. Reading some of those comments was very frustrating.

By: Maias

Maias — Mon, 07 Jan 2008 14:56:32 -0800

It is definitely true that lots of medicine has not been subjected to randomized, controlled trials -- and that many surgeries have never been trialed and they can be introduced without RCT's or any real evidence. however, the UK's National Institute on Health and Clinical Excellence (which uses evidence to decide what to cover for the UK's NHS) says evidence supports liver and lung transplantation (I didn't search further for others) and I think simply having evidence that someone who would otherwise have died lives much longer than the prognosis for their disease without a transplant when they get a transplant is pretty good evidence! I don't see why the NHS which needs to minimize use of expensive treatments would support transplants if there wasn't decent evidence.

By: NucleophilicAttack

NucleophilicAttack — Mon, 07 Jan 2008 14:59:03 -0800

Mental Wimp As the article I linked to quoted from, it's quite clear that for practical and ethical reasons, it is difficult at best to design large randomized trials that are sufficiently powered to pull out differences. Any number of studies have compared various therapies including transplantation, chemotherapy, etc. against each other, for treating a given (say, malignant) disease. Some of these are single-blind, some are double-blind, some are not blinded, some are retrospective. We can argue all day long about the feasibility or the defects in study design, and I'll be the first to acknowledge that all these studies have limitations. This does not mean that modern medicine has not gone to great lengths to study the efficacy, benefits, and drawbacks of transplantation medicine. I still find your claim that "the value of organ transplantation is, by and large, unproven and its use driven mostly by anecdote and observation" to be specious. Allogeneic hematopoietic stem cell transplantation happens to be my special area of expertise. The fact that allogeneic HSCT is still experimental for solid organ diseases is not under dispute; however, there exists strong clinical evidence going back for decades that it can be curative for MDS/AML, ALL, CML, and any number of inherited non-malignant hematopoietic diseases, specially the hemoglobinopathies.

By: Mental Wimp

Mental Wimp — Mon, 07 Jan 2008 15:04:33 -0800

and I think simply having evidence that someone who would otherwise have died lives much longer than the prognosis for their disease Well, I don't know who was on the panel that made the decision in the UK, but in the US kidney transplants are so well established that no one has the political clout to challenge them. At this point, the medical community has accepted them without rigorous evidence and claim that a trial at this point would be unethical. I suspect the same is true in UK. The problem is that the question of whether someone would have lived longer without a transplant can't be answered. (The philosophers call this the "counterfactual condition" and physicians are notoriously bad at predicting individual survival.) The only way to answer the question is with randomized trials. If you go look at the literature, you won't find any trials comparing transplantation to medical management for solid organs. The evidence doesn't exist. Notice I'm not saying they don't work to extend life or improve remaining life. I'm just pointing out that no one has done the rigorous studies necessary to show whether they do or don't. It's not my fault. Really.

By: small_ruminant

small_ruminant — Mon, 07 Jan 2008 15:04:37 -0800

simply having evidence that someone who would otherwise have died lives much longer than the prognosis for their disease without a transplant when they get a transplant is pretty good evidence! It's evidence of longer life, but not of a life everyone is up for living. If it's longer but miserable, some people don't find it's worth it. It bothers me how many people are pressured to undergo some grisly life-extending procedure without realistic explanations of what that extended life will be like, or despite being told the realistic expectations, if it's your freaked out parents and friends talking you into it. I suppose no friend or parent is really allowed to say, "Eh- sounds crappy. Maybe you should just die instead." My experiences have mostly been around chemo and cancer, but I think the problems are relevant to this article as well.

By: small_ruminant

small_ruminant — Mon, 07 Jan 2008 15:06:37 -0800

Regarding kidney transplants- yes, it's anecdotal, but I have seen 2 people go from really really sick, and planning their entire lives around available dialysis appointments, to healthy enough to bicycle and travel and work.

By: Mental Wimp

Mental Wimp — Mon, 07 Jan 2008 15:12:08 -0800

NucleophilicAttack I think my statement that the evidence is based on observation and anecdote stands. No randomized trials on solid organ transplantation have demonstrated efficacy either in survival or quality of life. And because of the selection biases, the results of observation are unreliable. Note that even these observations were not available when the use of kidney, heart, and liver transplantation became widespread. The studies followed their wide availability. And now we will never know the answer for sure, despite those involved declaring that they know the answer. As I point out, this problem isn't specific to transplantation. By the way, I still don't dispute the value of marrow and stem cell transplantation for many hematopoietic conditions (some of which you cite) has been proven in rigorous trials. This, I believe, is because of the long standing tradition in hematology/oncology of doing community based randomized trials before disseminating therapies. And kudos to them for it.

By: NucleophilicAttack

NucleophilicAttack — Mon, 07 Jan 2008 15:26:17 -0800

It's clear that you and I are talking at cross-purposes. You seem to believe that randomized trials are the only way to establish efficacy. The fact that a well-designed, well-powered and rigorously performed randomized trial is a powerful tool in our search for answers is, again, not under dispute. The fact that retrospective analyses, meta-analyses, case reports, and unblinded analyses have their limitations and biases is also not under dispute. That said, I continue to take issue with your initial representation of the issue as one in which the value of transplantation is "unproven" and driven by (you imply) the greedy elements of "big medicine." As I keep pointing out, just because the studies we do have are non-ideal, does not mean that nothing of value can be learned from them. That these studies were not performed prior to the introduction of transplantation therapies should not be surprising. As the book Puzzle People makes quite clear, the first series of operations were, of necessity, small in scale and performed on an experimental basis. Finally, as I pointed out before, the small number of patients and their spread over multiple centers across the U.S. makes it difficult to perform double-blind studies even if one really wanted to.

By: Mental Wimp

Mental Wimp — Mon, 07 Jan 2008 15:47:05 -0800

You seem to believe that randomized trials are the only way to establish efficacy. No, just that in this particular case where selection for the therapy is known to introduce intractable bias, observational studies are not very helpful. That these studies were not performed prior to the introduction of transplantation therapies should not be surprising. I was pointing out that studies were not done until transplants were widely used, not "prior to the[ir] introduction". And since some therapies have been studied rigorously prior to widespread use (see my previous comment about cancer therapies), your rationale is a weak one. As to whether "big medicine" is "greedy" I leave to you, as every business is interested in its economic well being. I just don't believe decisions about therapies should be left solely to those who benefit economically most directly. Once the therapies are established as efficacious, I would like physicians to make a great living off of them, as they clearly deserve.

By: Morrigan

Morrigan — Mon, 07 Jan 2008 16:15:15 -0800

Obligatory "My So-Called Lungs" link. Laura Rothenberg underwent a double lung transplant and recorded her experiences in a series of very moving and worthwhile audio recordings.

By: NucleophilicAttack

NucleophilicAttack — Mon, 07 Jan 2008 17:11:45 -0800

You simply have not addressed the fact that sufficiently powered randomized studies are basically impossible to do given the size, characteristics, and variability of the patient populations. As for whether there is 'intractable' bias or whether something of value can be learned from observational and retrospective studies, I continue to disagree that the studies we do have are somehow flawed beyond usefulness.

By: Mental Wimp

Mental Wimp — Mon, 07 Jan 2008 17:16:31 -0800

If the benefits are so obvious, it wouldn't take a very large trial to see them. If they are small enough to require huge trials, then I question their value given the expense and side effects, and insist that those trials need to be done. Cancer trials seem to be able to accrue enough to demonstrate value of chemotherapy, radiation, and, yes, even stem cell transplants. I don't believe I ever said that nothing of value can come from observational studies, just that big benefit/big risk questions should not hinge on the subjective evaluation of whether the observational study addresses the obvious biases that one faces in transplantation. It is the bias that is obvious, not the benefit, and thus the burden, scientifically, rests on those who claim benefit, it seems to me.

By: maxwelton

maxwelton — Mon, 07 Jan 2008 18:01:50 -0800

A family friend had a heart transplant when he was 60 and thinks it is the best thing that ever happened to him. He feels healthier now than he ever has. Anyway, a minor anecdotal point.

By: Camofrog

Camofrog — Mon, 07 Jan 2008 19:24:36 -0800

I remember hearing about somebody who got a transplanted heart and started having tastes in line with the donor. I've also heard that mechanical hearts are weird too. You see the people you love -- and your heart does not skip a beat. It has no connection to your emotions. Tin man.

By: Slithy_Tove

Slithy_Tove — Mon, 07 Jan 2008 19:54:25 -0800

Anyway, a minor anecdotal point. It should be pointed out that Amy's story is itself a 'minor anecdotal point', exactly equal in meaning to that of maxwelton's family friend. Amy Silverstein's experiences, and her reaction to them, may not be the same as others'. Take a look at the feedback on this US News story, mainly from other transplant recipients. These, too, are anecdotal experiences, different from Amy's, but no more or less valid. I was especially struck by this:

As chairman of a heart transplant support group, I have learned that anyone receiving a heart below the age of 40 or 50 is less happy than older folks—the younger, the more unhappy. This is due to the fact that they have not lived most of their life. Older folks are glad to have their life extended, and they deal more effectively with the medications and restrictions that come with the transplant. This differs with each individual, of course. People of all ages respond both negatively and positively, depending on their personality and their life experiences.

It sounds like old, sick folks compare their post-transplant life to their years of heart trouble, dialysis, liver failure—and they find it's better with their transplant. Young folks, though, compare their post-transplant life to their life before their original disease, when they were healthy. Not surprisingly, they find find it worse. Finally, bear in mind that Ms. Silverstein, despite her extensive medical experiences, is not medically trained, her book apparently has not been proofed by anyone who is medically trained, and there are some obvious errors, even in this brief extract. (For example, she did not go into 'ventricular fibrillation' in the restaurant. If she had, she never would have made it to the hospital.) We may take her story of her life, and her emotional reaction to it as true, but I would be wary of fully trusting the medical details. And thanks to Mental Wimp and NucleophilicAttack for the stimulating, articulate, and largely civil discussion of the problematic epistemology of transplantation medicine, which has relevance to much else in medicine as well.

By: drpynchon

drpynchon — Mon, 07 Jan 2008 23:19:20 -0800

I can't help but think you've wildly misinterpreted the transplant research available, Mental Wimp. You act as though people simply haven't looked at comparing medical management with solid organ allografts. Generally that sort of thinking limits you to talking about kidney transplantation versus dialysis as patient's receiving lung, heart, and liver transplants don't really have a medical option. Candidacy for the transplants in those cases practically depends on failure of medical management. To be listed as a class 1a candidate for a heart you need to either be on a ventilator with refractory pulmonary edema, have a continuous infusion of an ionotropic agent through a central venous catheter, or have a mechanical circulatory device already (like an artificial heart). Folks in that situation have already been managed for a long time with your run of the mill medical management so at a certain point you're basically comparing a group treated with a solid organ allograft versus a hypothetical group of people who are otherwise dead. There are limits to what research trials can be designed for both ethical and practical reasons as you know, but even despite that, there's still a reasonable bit of data out there even when it comes to kidney transplantation. None of it is randomized or blinded in the conventional sense to be sure. But there is prospective data on dialysis patients followed at the time of transplant listing comparing folks that got off the list to folks that didn't, and most people are willing to take that data for what it's worth in regards to approximating randomization.^1,2,3,4,5 Patient's who are transplanted have about a 40% relative reduction in yearly mortality. Now you can sit there and blow of a mountain of retrospective or prospective non-randomized data, invoking the standard assumed biases, but at a certain point that approaches closed-mindedness when there's really no alternative research modality available. Moreover, the scientific standard you've set for your self effectively makes assessing a soft, amorphous outcome like quality of life (which is crucial, and the real subject of the FPP) essentially impossible. None the less, there's plenty of research even in the kidney transplant population that shows substantial, statistically significant improvements in quality of life regardless of mortality outcome.^6,7,8 Consider the last link to a meta-analysis by Drew et al. of over 200 articles just on quality of life in kidney transplants. Among the prospective studies they looked at, every single one of them found a statistically significant improvement in quality of life from pre- to post-transplant. If you grant that observational studies have some value, at what elevation does the mountain of observational data become adequate for your standards is what I'm asking I guess. Either you haven't been exposed to all the data out there or you and I (and most clinical researchers I know) must have a wildly different expectations on what's a reasonable threshold. And again, that relates really to the subject of renal transplantation more than other organs in which criteria for getting an allograft make your presumptions almost moot.

By: NucleophilicAttack

NucleophilicAttack — Tue, 08 Jan 2008 05:38:16 -0800

Mental Wimp The power of a study depends not only on the group size, but also on the expected variance (assuming gaussian distributions for simplicity.) I need not point out that contrary to studies for say, an anti-hyptertensive agent where it is possible to recruit tens of thousands and then organize large, near-uniform cohorts for testing across multiple centers, the situation with transplant is: (1) comparatively few patients undergoing transplant (and those spread out over any number of centers and years) (2) high variability in the patient population, who while all very sick, are usually sick with any number of varying and different comorbidities (3) high variability in the organs available (live vs. cadaver, organ size, HLA-matching, etc. being merely a few of many possible differences) (4) high variability in the process of transplant: it is quite clear that each center has expertise with particular variations for transplanting say, bone marrow stem cells. How the graft is prepared, the immunosuppression and anti-fungal prophylaxis, etc. will vary across centers, according to what that particular group has found to work the best in their hands. The fact is, transplantation is a uniquely complex and difficult therapy with far more built-in variables than say, giving a single anti-hypertensive agent to a selected population. All of which is a roundabout way of saying that the large benefits can be difficult to pull out of the small group sizes that are practically available, simply due to even larger variabilities inherent to transplant.

By: Mental Wimp

Mental Wimp — Tue, 08 Jan 2008 12:02:14 -0800

None of the arguments you offer make it impossible to do randomized trials. My daughter had a Wilm's tumor, a rare (500-a-year) childhood cancer and was randomized into the National Wilm's Tumor Study, which at the time randomized almost every child diagnosed in North America because pediatric oncologists wanted to do it and were organized. It is specious to say that because a trial takes a long time or is expensive or difficult then, what the hell, let's just start giving the therapy to everyone, even if we don't know whether we're doing net harm or net good. The heterogeneity argument is spurious as well, since the therapy is given to all regardless of that variability, so the practice should be judged on those grounds. In fact, it is that variability that makes it impossible for someone to say whether good has been done without a randomized control group. You essentially make the argument for a randomized control. You may or may not realize that I've encountered the identical claims about not needing randomized trials in every medical field that I've done trials in. The same specious reasoning and the same cock-suredness that somehow, magically, the practitioners know what works without adequate controls is widespread. The only time the community reverses its stance is when someone manages to do a trial and demonstrate to them that they are doing harm. This happened with BMT and breast cancer, antiarrhythmics for post-MI patients, toxoplasmosis prophylaxis in AIDS patients, hormone replacement therapy, etc., etc., etc. Unfortunately, it is the exception that someone does a trial because those who control the funding and patients have already convinced themselves and claim lack of equipoise. Being sure isn't the same as having proof and to visit painful and dangerous therapies without proof that net benefit results should be unethical, but we haven't evolved that far yet.

By: Mental Wimp

Mental Wimp — Tue, 08 Jan 2008 12:30:12 -0800

drpynchon This is my last post on this topic, as I don't think I'm going to convince you or NucleophilicAttack by blathering on about this. All I can say is that only someone already convinced that transplantation works would be convinced by the studies you cite. Note, for example, that in ref 6 the comparison groups are those that survived transplant and those still getting dialysis. Two problems: 1) transplant surgery culled out the weak ones among those considered candidates by killing them off, and 2) the dialysis group contains people not considered candidates for transplant for one reason or another. Now, I know that you can attempt to deconfound the comparison as any good analyst would, but I also know that in the case of subjective selection, it is impossible to avoid residual confounding, and in this case, doubly so. It would be interesting to know what the functioning would have been of the patients who got transplants, had they not received them. (Including those that died of the procedure; notice the abstract doesn't even mention death). But we will never know. The literature on the selection of patients for risky surgery and the inability to predict it using objective measures is long and notorious. For example, the original studies on intracranial bypass with an intention to treat analysis showed no benefit once all mortality including surgical mortality was accounted for in a randomized trial. Ignoring the surgical mortality and selection effects seemed to indicate a benefit, as would any observational study mounted. As I say, none of the arguments either of you offer are unique to this field and have been offered in multiple other medical fields to rationalize not doing trials. I'm not going to change it with my little postings here, but I thought Mefites ought to at least be aware that outside the transplant world there are serious questions about whether we know people benefit. Unless treating physicians start thinking skeptically, though, we will see this situation repeated ad nauseum as new technologies and techniques emerge.

By: NucleophilicAttack

NucleophilicAttack — Tue, 08 Jan 2008 13:31:07 -0800

You've resorted to straw-man arguments here. Where did I claim that anyone is cock-sure about the relative benefits of transplant vs. other protocols? Your basic argument is "because of bullheadedness, stupidity, arrogance, malice, greed, laziness, whatever, the medical establishment has bent over backwards to avoid doing double-blind trials in the field of transplantation; the studies that they have done are hopelessly biased, entirely uninformative, and not worth the paper they're printed on." (Incidentally, given the prevalence of large, multi-center, double-blind studies for everything from proton pump inhibitors to anti-angiogenesis agents, do you really believe that transplant physicians and the NIH study groups that fund them, are simply willfully ignoring double-blind study designs?) By contrast, my basic argument is simply that "the basic characteristics of the organ transplant population and the variabilities involved make double-blind trials infeasible to do. That said, other types of clinical research are also of value, and can tell us whether transplant is a useful therapy or not." As for your daughter, you have most certainly not answered my argument. Although Wilm's Tumor is rare overall, it is the fourth most common pediatric tumor (Cancer. 1997 Dec 15;80(12):2321-32.). Additionally, it is found in a relatively homogenous population of pediatric patients with (by definition) a short and comparatively simple medical history who are tightly clustered in age. It is specious to point to a Wilm's Tumor trial, proclaim "see, it is possible!" and suggest that blinded trials for organ transplantation have not been done because transplant physicians are lazy, impatient, greedy or just plain stupid. As I keep pointing out and you keep ignoring, organ transplantation is an enormously complex medical procedure where the variability I listed above is merely a small fraction of the total number of variables; this renders the trials you want to see infeasibly expensive, or just plain infeasible period. The heterogeneity argument is spurious as well, since the therapy is given to all regardless of that variability, so the practice should be judged on those grounds. In fact, it is that variability that makes it impossible for someone to say whether good has been done without a randomized control group. You essentially make the argument for a randomized control. Actually, you're making my argument for me. The variability impedes our ability to assess efficacy, safety, etc. overall. The variability means that double-blind studies are often infeasible for this particular therapy. Consequently, we resort to other study designs.

By: drpynchon

drpynchon — Tue, 08 Jan 2008 13:51:57 -0800

I understand we're going in circles here but you're picking and choosing articles to criticize. A quality of life study is obviously going to throw out people that don't survive surgery. Dead people don't fill out questionaires all that well, but that's irrelavent because the question they seek to answer doesn't have to do with mortality (which by the way, the other studies I cite that you choose to ignore do address), but whether people are happy with their lifestyle and have improved day-to-day functionality following transplantation. And the answer to that is that on average they do. If you look at the mortality studies, surgical mortality is included in the data. Moreover they don't compare patient who are and are not candidates for transplant as you speciously suggest. Multiple studies compare patient's on dialysis from the moment they are listed. In these two groups, averaged over time, getting off the waiting approaches a random process because exclusionary criteria have already been addressed. You're not going to get a better control than that. So if you choose to disregard that data because we haven't been able to clone dialysis patient's and refuse one twin a transplant so as to have a control group, that's your perogative. But picking and choosing which articles to attack out of context is a bit disingenuous.

By: homunculus

homunculus — Sun, 13 Jan 2008 11:27:43 -0800

Hopes of custom-built organs as scientists create beating heart