The latest option for losing weight via surgically reducing stomach size: Having most of your stomach cut away and taken out by a procedure performed mostly through your mouth and down your throat. (A bit of the work is done through small slits in your abdomen.) What little is left of the stomach is then stitched up to form a mini-stomach, with the obvious result that it only takes a relatively small amount of food to fill it up. Other, more-established options for stomach surgery include the gastric bypass, a more extensive procedure in which in addition to the stomach being downsized it is also reconnected to a shorter span of intestine, cutting down on calorie absorption, and the lap band, in which much of your stomach is squeezed off by an adjustable band.
These procedures are often discussed as if they have been proven safe and effective in studies. But keep some points in mind when considering how "proven" a surgical technique is. There are (with a very few exceptions) no good, ethical ways to conduct randomized, blind trials of surgical procedures. It would be hard enough to do the randomization, in which patients are (to oversimplify a bit) randomly assigned to either a group that will receive the surgical procedure or a group that will not, because not many patients are willing to have surgical decisions made for them by the toss of a coin. But even if that issue were overcome, the real problem would be with blinding, which means patients don't know which group they're in. It's not easy to get people to not know whether they've had surgery or not--and even if you could pull it off it's even tougher to do it in a way that doesn't run afoul of ethical considerations. (It's been attempted, believe it or not, but hell was raised.) The result is that studies of newer surgical procedures are mostly observational studies, which means doctors just note how patients seem to be doing. (I'm not counting animal studies. Neither should you. No matter what researchers say, on average these studies don't translate well to humans.) Some procedures that have been widely performed for many years get "case control" (epidemiological) studies, which look back at groups of patients who have received the treatment and compare them to groups who have not. While you can't fully tell how trustworthy a study is just by noting what type of study it is--it's wise to consider all medical studies at least potentially somewhat untrustworthy--as a rough generalization randomized, blind trials tend to be more trustworthy than case-control studies, and observational studies are the bottom of the barrel, though to be sure there are lots of exceptions and qualifications to this pecking order.
In short, the fact that gastric bypass, and, to a lesser extent, lap band procedures, have been found in case-control studies and many observational studies to be fairly safe and effective should not be taken very seriously. These types of studies can be subject to intense biases on both the parts of doctors and patients--they generally want the procedures to succeed, and may distort their observations and do a poor job of recording all relevant data. Researchers also typically don't have access to all the data they need to fully analyze the situation. (For example, in the New England Journal of Medicine article I reference just above, the authors to their credit note that the study ignores the possibilities--likelihoods, I'd reckon, though the authors beg to differ--that people who had the surgery got much more or better medical attention afterward than other obese people get, and that they may have been healthier to begin with.) The procedures are a huge money-maker for surgeons, and the patients are often desperate to lose the weight and may be eager to convince themselves and others that they've done the right thing and that things are going to work out well. These biases, which can be and often are devastating to the reliability of medical studies, are exactly what randomized, blind studies attempt (if not always successfully) to eliminate. That's why many surgical procedures are widely accepted as safe and effective, only to eventually prove themselves not so safe and/or less effective than other, less invasive and less risky treatments--the list includes many types of heart-related operations, back-pain-related operations, brain surgeries, and on and on.
This newest stomach-reduction procedure has been performed on one person so far. And yet surgeons just about everywhere will soon be able to perform it on anyone they deem suitable, providing nothing obviously terrible happens immediately to this one patient as a result. True, these sorts of "laparoscopic" (performed through small incisions and/or through the mouth, using a tiny camera and light to allow the surgeon to see what's going on in there) procedures tend on average to be less risky than conventional, large-incision versions of the same surgery, but there can be reasons why they are sometimes less safe and/or less effective in some ways--for example, the restricted access and vision may result in a sloppier job of cutting or stitching, or in missing problems with bleeding.
And there are reasons to question whether the people who are getting these procedures really need them enough to justify the risks. (Though the twice-aforementioned NEJM study found that overall death rates went down for obese people who had gastric bypass surgery due to fewer deaths from heart disease, diabetes and cancer--findings that for a number of reasons I suspect may exaggerate the benefits of the procedure--around one percent died from the surgery itself shortly after the operation, and many had complications.) The people who sign up for these operations are typically obese people who have tried to lose the weight through diet and exercise but have failed, and whose health appears to be at some risk. But trying to compare the potential payoff from trying to diet and exercise to the likely benefits of surgery is a bit of a fixed contest. I've been studying the question of why people fail with diets and exercise, and it's clear that the success rates would likely be much, much higher if overweight people weren't getting such almost uniformly terrible advice about how to diet and exercise, and if their motivation to lose weight through dieting and exercise weren't on average so low. Why is their motivation often so low? For one thing, they keep hearing from many researchers and obesity experts that they'll probably fail with diet and exercise, and for another they've been led to believe that surgery provides a much easier and surer option that will provide all the same benefits of a successful diet and exercise program without any of the work--these procedures essentially are intensely marketed much the way cosmetic surgery is hawked, because they're similarly ridiculously profitable. (Another issue is whether the success rate for dieting and exercising is really anywhere near as low as we've been told--but that's a more complicated story.) Meanwhile, the success and benefits of surgical weight-loss keep getting pumped up through studies that are likely somewhat biased and otherwise flawed.
I don't doubt there are obese people who, when the whole picture is soberly assessed, might be making a reasonable decision to undergo one of the procedures. But I suspect it's a fraction of the number of people who are actually getting the surgeries. I was especially appalled to see a big and very well-researched and well-written cover story in the Atlantic earlier this year on the subject of obesity essentially advocate for, or at least seriously suggest the idea of, the government putting its anti-obesity money into handing out gastric bypass surgery for the obese, presumably instead of into research, education, good-nutrition programs, more-exercise initiatives and other anti-obesity public-health initiatives. The article, which for sure in many ways was terrific, more or less declared dieting and exercise to be a waste of time--a point of view which is pushed by many published medical studies relying on highly biased and flawed set-ups (as evidenced, for example, by the fact that findings from these studies widely and sometimes sharply conflict), but which flies in the face of the significant documented success rates that hundreds of real-world programs have achieved with obese people (and which has also been backed up by other published studies, for what it's worth).
I think this sort of give-up-on-dieting-and-exercise-and-hold-out-for-surgery(-or-a-pill) thinking is dangerous, and is in fact a contributing factor to the obesity epidemic. If you're thinking of getting some form of stomach-reduction surgery, I'd urge you to do some more research into the possible complications and into dieting and exercising options, and to discuss what you find with your doctor. And if your doctor is pushing you toward the surgery and especially if he seems biased toward it, try a second opinion from a doctor you have good reason to believe has an objective view about both diet-and-exercise programs and surgical alternatives. Many, many obese people have shed the weight and kept it off through dieting and exercise. Shouldn't you be absolutely sure you've given dieting and exercise your very best shot under the right program before you have one or even two of your major organs hacked up and extensively rejiggered?
Sunday, August 15, 2010
Wednesday, July 14, 2010
Can Pregnant Moms Program Babies for Obesity?
A new study claims it shows that the children of pregnant mothers who put on lots of weight are much more likely to be obese years later than the children of mothers who don't put on as much weight in pregnancy. The announcement of the findings has triggered comments from other researchers and experts suggesting that this study is simply the latest in a series of studies supporting the notion that women who eat too much during pregnancy are placing their children at greater risk of obesity.
Nope. This new study tells us very little, and none of the others tells us much, either. The only sort of study that would have at least a small chance of giving us some real insight into the effect of eating during pregnancy on children's lifelong tendency toward obesity would be one that randomly assigned many, many pregnant women to either a group that was somehow made to put on a relatively large amount of weight during the pregnancy, or a group that was somehow made to put on a relatively small amount of weight. Then the study would have to follow the weight gain of the children in the two groups for a few decades. Such a study would still be plagued with potential confounders, since, for example, it wouldn't be blinded (the women and the researchers would likely know which group each woman was in), and the two groups of mothers might start behaving very differently from one another because of the particular way in which their weight had been controlled. But it doesn't matter, because no one is likely to do that study--I can't imagine researchers being able to line up enough pregnant women willing to participate, and even if they did that they'd be able to effectively control the two group's weight gains during pregnancy, or even if they could that the whole project would make it through ethics review boards. So all researchers can do is track the weight gain of a bunch of pregnant women, wait to see what happens to their children, and then go back and look for links. This approach almost always leads to utterly unreliable results, because we have no way of knowing what causes what in the resulting observed links, and indeed the links themselves are often merely artifacts of bad data and/or bad analysis.
All these pregnant-weight-gain studies really show at best is that mothers who tend to put on too much weight are more likely to have children who put on too much weight. Not only is that painfully unsurprising, but it's tremendously useless information. It doesn't tell us whether that's happening because of a genetic predisposition for weight loss that gets handed down from parent to child, or because mothers tend to pass healthy or unhealthy eating habits onto their children in some way, or because exposing very young children or possibly even fetuses to excessive intakes of food or to less-healthy foods somehow changes their metabolisms or alters their appetite mechanisms. (That first study's conclusions seem to vaguely imply the latter, for what that's worth, which I think is very little.) The studies give even fewer clues as to what ought to be done about the situation. If it's genetic, there's probably little point in addressing what pregnant mothers eat, which seems wrong. If the mother's eating is programming the child in the womb in some way, then what the mother eats during pregnancy becomes critical--and what and how the child eats after birth is not so important, a conclusion that defies everyday observation and common sense. If the mother's weight gain is "transferred" to the child via the food attitudes and habits that the child picks up from a mother who simply doesn't do a good job of controlling her weight, then genes or what happens during pregnancy is largely irrelevant. I think there's a pretty good chance that what we're seeing here is some combination of the three--genes, changes that take place during pregnancy, and (probably especially) family eating habits passed on to the child later on. But the studies don't help pin any of this down in the least.
So what should pregnant mothers take away from all this? Come on, you know the answer to that. They should eat sensibly (and as per doctor's advice), avoid either excessive or insufficient weight gain during pregnancy (unless the doctor orders otherwise), and most important (in my opinion and in the opinion of most of the many experts I've interviewed on this subject) work hard to transmit generally accepted good eating habits to their children, starting from birth and continuing on through all of childhood. (If your doctor disagrees with that last bit, get a new doctor.) I doubt we'll ever see a study that provides convincing evidence that doing anything else makes sense.
Nope. This new study tells us very little, and none of the others tells us much, either. The only sort of study that would have at least a small chance of giving us some real insight into the effect of eating during pregnancy on children's lifelong tendency toward obesity would be one that randomly assigned many, many pregnant women to either a group that was somehow made to put on a relatively large amount of weight during the pregnancy, or a group that was somehow made to put on a relatively small amount of weight. Then the study would have to follow the weight gain of the children in the two groups for a few decades. Such a study would still be plagued with potential confounders, since, for example, it wouldn't be blinded (the women and the researchers would likely know which group each woman was in), and the two groups of mothers might start behaving very differently from one another because of the particular way in which their weight had been controlled. But it doesn't matter, because no one is likely to do that study--I can't imagine researchers being able to line up enough pregnant women willing to participate, and even if they did that they'd be able to effectively control the two group's weight gains during pregnancy, or even if they could that the whole project would make it through ethics review boards. So all researchers can do is track the weight gain of a bunch of pregnant women, wait to see what happens to their children, and then go back and look for links. This approach almost always leads to utterly unreliable results, because we have no way of knowing what causes what in the resulting observed links, and indeed the links themselves are often merely artifacts of bad data and/or bad analysis.
All these pregnant-weight-gain studies really show at best is that mothers who tend to put on too much weight are more likely to have children who put on too much weight. Not only is that painfully unsurprising, but it's tremendously useless information. It doesn't tell us whether that's happening because of a genetic predisposition for weight loss that gets handed down from parent to child, or because mothers tend to pass healthy or unhealthy eating habits onto their children in some way, or because exposing very young children or possibly even fetuses to excessive intakes of food or to less-healthy foods somehow changes their metabolisms or alters their appetite mechanisms. (That first study's conclusions seem to vaguely imply the latter, for what that's worth, which I think is very little.) The studies give even fewer clues as to what ought to be done about the situation. If it's genetic, there's probably little point in addressing what pregnant mothers eat, which seems wrong. If the mother's eating is programming the child in the womb in some way, then what the mother eats during pregnancy becomes critical--and what and how the child eats after birth is not so important, a conclusion that defies everyday observation and common sense. If the mother's weight gain is "transferred" to the child via the food attitudes and habits that the child picks up from a mother who simply doesn't do a good job of controlling her weight, then genes or what happens during pregnancy is largely irrelevant. I think there's a pretty good chance that what we're seeing here is some combination of the three--genes, changes that take place during pregnancy, and (probably especially) family eating habits passed on to the child later on. But the studies don't help pin any of this down in the least.
So what should pregnant mothers take away from all this? Come on, you know the answer to that. They should eat sensibly (and as per doctor's advice), avoid either excessive or insufficient weight gain during pregnancy (unless the doctor orders otherwise), and most important (in my opinion and in the opinion of most of the many experts I've interviewed on this subject) work hard to transmit generally accepted good eating habits to their children, starting from birth and continuing on through all of childhood. (If your doctor disagrees with that last bit, get a new doctor.) I doubt we'll ever see a study that provides convincing evidence that doing anything else makes sense.
Wednesday, July 7, 2010
Is Long Life Mostly In the Genes?
Update: A problem with the study that I describe in this post has surfaced within the scientific community, and has even received mass-media attention. It's a technical problem of exactly the sort I warn about in the post. The only thing that's unusual here is that the problem has been called out prominently.
A new study has shown that living into your nineties and beyond is a matter of having the right genes, according to recent headlines. The technique that the researchers employed to identify the genes of long life is much the same one behind many of the discoveries of links between genes and traits or genes and disorders that we hear about frequently. To oversimplify a bit, the game involves looking at many genes in a large group of people who have some trait in common, and then trying to spot which particular genes turn up more frequently in these folks than in a large group people who don't have the trait.
I recommend not paying much attention to this study, or to most studies that purport to have identified key genes behind some important trait or disorder, and for a few reasons. First of all, this basic gene-linking technique, although an impressive one and getting better, is still beset with a variety of inherent limitations and potential flaws that often lead to simply misidentifying genes as being closely linked to a trait in most people when they are not, and misses many and possibly most of the genes that actually influence the trait. Part of the problem is that the technique is a highly statistical one based on probabilities involving all sorts of manipulations that can leave the picture convoluted and murky. In addition, the very notion that a relatively small number of genes is likely to play a huge role in determining a trait or disease risk is for the most part a mistaken one, or at best a gross oversimplification. Genes act not alone or even as a small band, but rather as a vast orchestra. Even more confusing, genes can be "turned off" so that they might as well not be there, or partly turned on so that they contribute only weakly to a trait or disease risk. What turns genes on and off? Each other, the environment, other molecules in our cells, and strips of DNA that aren't even parts of genes. It gets worse: Genes can appear in single form, or in multiple copies that increase their influence in ways most gene tests don't detect. They can pop out of their slot in the genome, replicate themselves, and then reinsert themselves somewhere else in the genome. They can flip around backwards, which also isn't detected by gene tests, even though a backwards gene can behave differently. Throw in the fact that genes can be changed by viruses, and that any protein made by a particular gene can do different things in different people, or different things in the same person at different times depending on what else is going on in the body, and you've got complexity of such staggering breadth and depth that scientists who are being honest about the situation admit they'll be lucky to make a small dent in the task of sorting it all out in their lifetimes.
Consider: A 2009 study of about 6,000 people came up with a technique for predicting the height of a person based on looking at the 54 genes most closely linked to height. The results turned out to be one-tenth as accurate as averaging the heights of both parents and adjusting for sex, a technique introduced in 1886 by statistician Sir Francis Galton. University College Dublin biomolecular researcher Helen Colhoun and colleagues have estimated that 95 percent of studies that find gene links are just plain wrong. Harvard genetics researcher Joel Hirschhorn and colleagues surveyed the medical literature on 166 published genetic links to illness that were each examined in at least two other published studies, and found that only six of the links--less than four percent--held up in all the studies. John Ioannidis of Tufts University Medical School has calculated the average odds of a gene-link study being right at one out of hundreds, or worse, depending on the disease. In the case of schizophrenia, for example, Ioannidis reckons a one out of 2,000 chance of a gene-link study being right. His estimates suggest you would have almost as good a chance of identifying some types of genuine gene links by throwing darts at a diagram of the relevant sections of the human genome as you would by reading research journals. Researchers claim their hit rate has improved quite a bit in the past few years, but we won't know the extent to which that's true for a while to come. Needless to say, all these substantial uncertainties and vagaries often get swept under the carpet in the reported findings of an exciting new study, and are almost always ignored in the mass-media reports.
None of this is to say that the study in question here didn't correctly identify many genes that may in fact in some cases be potentially important contributors to living a very long life. But even if the claim is largely or at least partly right, it's still a misleading one. When we hear it, we assume that we'll need many or most of these genes to have a good shot at a long, healthy life--and that's an absolutely unwarranted conclusion. People who live extraordinarily long lives need everything to go in their favor, including many things that may be largely irrelevant to those of us who hope to keep decent health "merely" into our 80s. Assuming we need the genes common in people who live to be 100 may be like assuming a good-performing car needs to have the components common to race cars.
Even if it does indeed help quite a bit to have the right genes in order to live a long and healthy life, it also helps to get a lot of other things right. What has come through from all the genetic studies more clearly than anything else is that for most of us genes really don't influence your destiny as much as, or at least any more than, your behavior does. Folks, if you want to live relatively long lives, and perhaps more importantly stay relatively healthy late into that life, there is powerful evidence that eating sensibly, exercising, breathing clean air, avoiding undue stress, and refraining from obviously bad habits such as smoking, heavy drinking and not wearing seatbelts, can for many and possibly most of us trump genes. In fact, for all we know, some of the genes that the very-long-lived had in common in this study were genes that influence healthy behaviors--in which case anyone engaging in the behaviors would get the same benefits, whether they had the genes or not.
Your fate is probably not genetically sealed--it is much more likely that your health is to a large extent under your control. Don't let announcements of marvelous gene-link breakthroughs lead you to abdicate that responsibility.
A new study has shown that living into your nineties and beyond is a matter of having the right genes, according to recent headlines. The technique that the researchers employed to identify the genes of long life is much the same one behind many of the discoveries of links between genes and traits or genes and disorders that we hear about frequently. To oversimplify a bit, the game involves looking at many genes in a large group of people who have some trait in common, and then trying to spot which particular genes turn up more frequently in these folks than in a large group people who don't have the trait.
I recommend not paying much attention to this study, or to most studies that purport to have identified key genes behind some important trait or disorder, and for a few reasons. First of all, this basic gene-linking technique, although an impressive one and getting better, is still beset with a variety of inherent limitations and potential flaws that often lead to simply misidentifying genes as being closely linked to a trait in most people when they are not, and misses many and possibly most of the genes that actually influence the trait. Part of the problem is that the technique is a highly statistical one based on probabilities involving all sorts of manipulations that can leave the picture convoluted and murky. In addition, the very notion that a relatively small number of genes is likely to play a huge role in determining a trait or disease risk is for the most part a mistaken one, or at best a gross oversimplification. Genes act not alone or even as a small band, but rather as a vast orchestra. Even more confusing, genes can be "turned off" so that they might as well not be there, or partly turned on so that they contribute only weakly to a trait or disease risk. What turns genes on and off? Each other, the environment, other molecules in our cells, and strips of DNA that aren't even parts of genes. It gets worse: Genes can appear in single form, or in multiple copies that increase their influence in ways most gene tests don't detect. They can pop out of their slot in the genome, replicate themselves, and then reinsert themselves somewhere else in the genome. They can flip around backwards, which also isn't detected by gene tests, even though a backwards gene can behave differently. Throw in the fact that genes can be changed by viruses, and that any protein made by a particular gene can do different things in different people, or different things in the same person at different times depending on what else is going on in the body, and you've got complexity of such staggering breadth and depth that scientists who are being honest about the situation admit they'll be lucky to make a small dent in the task of sorting it all out in their lifetimes.
Consider: A 2009 study of about 6,000 people came up with a technique for predicting the height of a person based on looking at the 54 genes most closely linked to height. The results turned out to be one-tenth as accurate as averaging the heights of both parents and adjusting for sex, a technique introduced in 1886 by statistician Sir Francis Galton. University College Dublin biomolecular researcher Helen Colhoun and colleagues have estimated that 95 percent of studies that find gene links are just plain wrong. Harvard genetics researcher Joel Hirschhorn and colleagues surveyed the medical literature on 166 published genetic links to illness that were each examined in at least two other published studies, and found that only six of the links--less than four percent--held up in all the studies. John Ioannidis of Tufts University Medical School has calculated the average odds of a gene-link study being right at one out of hundreds, or worse, depending on the disease. In the case of schizophrenia, for example, Ioannidis reckons a one out of 2,000 chance of a gene-link study being right. His estimates suggest you would have almost as good a chance of identifying some types of genuine gene links by throwing darts at a diagram of the relevant sections of the human genome as you would by reading research journals. Researchers claim their hit rate has improved quite a bit in the past few years, but we won't know the extent to which that's true for a while to come. Needless to say, all these substantial uncertainties and vagaries often get swept under the carpet in the reported findings of an exciting new study, and are almost always ignored in the mass-media reports.
None of this is to say that the study in question here didn't correctly identify many genes that may in fact in some cases be potentially important contributors to living a very long life. But even if the claim is largely or at least partly right, it's still a misleading one. When we hear it, we assume that we'll need many or most of these genes to have a good shot at a long, healthy life--and that's an absolutely unwarranted conclusion. People who live extraordinarily long lives need everything to go in their favor, including many things that may be largely irrelevant to those of us who hope to keep decent health "merely" into our 80s. Assuming we need the genes common in people who live to be 100 may be like assuming a good-performing car needs to have the components common to race cars.
Even if it does indeed help quite a bit to have the right genes in order to live a long and healthy life, it also helps to get a lot of other things right. What has come through from all the genetic studies more clearly than anything else is that for most of us genes really don't influence your destiny as much as, or at least any more than, your behavior does. Folks, if you want to live relatively long lives, and perhaps more importantly stay relatively healthy late into that life, there is powerful evidence that eating sensibly, exercising, breathing clean air, avoiding undue stress, and refraining from obviously bad habits such as smoking, heavy drinking and not wearing seatbelts, can for many and possibly most of us trump genes. In fact, for all we know, some of the genes that the very-long-lived had in common in this study were genes that influence healthy behaviors--in which case anyone engaging in the behaviors would get the same benefits, whether they had the genes or not.
Your fate is probably not genetically sealed--it is much more likely that your health is to a large extent under your control. Don't let announcements of marvelous gene-link breakthroughs lead you to abdicate that responsibility.
Thursday, July 1, 2010
The Trouble with Medications
One recent set of headlines noted that an experimental, cutting-edge drug for the difficult-to-treat disease hepatitis C isn't looking good for FDA approval because there's evidence it can harm patients without much helping them. That's terrible news for hepatitis C sufferers, of course, but most of us might just shrug, figuring that's exactly the sort of outcome we might well expect from many and perhaps most unproven, high-tech treatments that are undergoing trials. What the public is much less aware of is that the same dubious benefit-to-risk situation applies to many of the drugs that are already widely prescribed. In just the past few days we've read headlines about how the diabetes drug Avandia, which has been taken by more than a million people, has now been strongly linked by big studies to potentially fatal heart disorders and strokes. And also making the news is a smaller study that suggests testosterone gel--increasingly commonly prescribed to older men to counter some of the debilitating effects of aging, including loss of bone density, muscle mass, mobility, energy and libido--may be strongly linked to heart disorders, at least in much older men with low mobility.
This isn't just some small run of bad luck for the drug world. These sorts of problems are inherent to the very nature of drugs. Our bodies function via chemical "pathways" in which a vast number of proteins made by our genes interact with each other in ways so staggeringly complex that scientists struggle mightily to identify small pieces of the picture. When you take a drug, the hope is that it will go in and interrupt or boost some isolated part of a pathway that's contributing whatever disorder you may be suffering from. But disorders can rarely be neatly pinned down to a simple pathway, which means there isn't a clean target for the drug, which means the drug isn't likely to hit the problem head on. What's more, everyone has different genes, and even when we have the same relevant genes they may be turned "on" or "off" in different ways in different people, so that our pathways our different, which means that even when a drug is somewhat effective in one person it might not be so in another. Even worse, the drug is almost certainly affecting other pathways that are important to our health, with the effects rippling through the body in ways that may well cause harm. These basic problems are why we've seen a stream of much-hyped, widely used drugs yanked from the market after years, leaving behind a trail of people who weren't much helped, or of people who suffered or even died from the drugs. Vioxx is probably the best-known example from the past several years, but recent headlines have listed many others.
Indeed, it would be miraculous if a drug could go in, completely solve a problem, and do nothing else--virtually no drugs have ever been found that pull that trick off. Instead, the vast majority of our drugs have much messier effects on us: they sort of help some people, hurt others, and don't do much of anything for yet others. Even established, major drugs don't work on 40% to 75% of people, according to a 2005 review paper in The New England Journal of Medicine, and the variation in effectiveness and risk of side-effects tends to be much greater for newer, less-proven drugs. The picture gets even worse when you're talking about patients who are on multiple drugs, which can react with each other in any number of ways that are rarely well understood and often altogether unstudied. We don't get all this from the findings of most studies, because they tend to report averages, and are often presented in a way that make it sound as if a drug can do a lot for you, with only some chance of causing you problems. That may be sort of true, but there's really no way of getting around the fact that for most drugs you're rolling the dice to some extent as to whether the drug is going to help or hurt, if it does anything at all. There's hope genetic tests will eventually boost the odds further in your favor, but right now the claims you hear in the news that this is happening today is mostly hype, with just a few exceptions.
I want to make it clear I am in no way advocating pressuring your doctor to take you off any of your drugs--doctors admit in surveys to often succumbing to patient pressure on some drug decisions even if they don't think the decision is medically best for the patient--and I most certainly don't want anyone stopping drugs on their own. But there's no reason why you shouldn't ask your doctor to explain in more detail how likely a drug is to help, how likely it is to hurt, and why he thinks it's worth it. By the same token, you might want to know what applicable drugs she's decided aren't right for you, and why. Why shouldn't you be involved in a decision that essentially involves placing a bet on risks and benefits to your health? I always bow to my doctor's judgment, but she's willing to explain how she's arrived at it, and she's interested in getting my input when it's a matter of weighing the odds, as is usually the case with medications.
This isn't just some small run of bad luck for the drug world. These sorts of problems are inherent to the very nature of drugs. Our bodies function via chemical "pathways" in which a vast number of proteins made by our genes interact with each other in ways so staggeringly complex that scientists struggle mightily to identify small pieces of the picture. When you take a drug, the hope is that it will go in and interrupt or boost some isolated part of a pathway that's contributing whatever disorder you may be suffering from. But disorders can rarely be neatly pinned down to a simple pathway, which means there isn't a clean target for the drug, which means the drug isn't likely to hit the problem head on. What's more, everyone has different genes, and even when we have the same relevant genes they may be turned "on" or "off" in different ways in different people, so that our pathways our different, which means that even when a drug is somewhat effective in one person it might not be so in another. Even worse, the drug is almost certainly affecting other pathways that are important to our health, with the effects rippling through the body in ways that may well cause harm. These basic problems are why we've seen a stream of much-hyped, widely used drugs yanked from the market after years, leaving behind a trail of people who weren't much helped, or of people who suffered or even died from the drugs. Vioxx is probably the best-known example from the past several years, but recent headlines have listed many others.
Indeed, it would be miraculous if a drug could go in, completely solve a problem, and do nothing else--virtually no drugs have ever been found that pull that trick off. Instead, the vast majority of our drugs have much messier effects on us: they sort of help some people, hurt others, and don't do much of anything for yet others. Even established, major drugs don't work on 40% to 75% of people, according to a 2005 review paper in The New England Journal of Medicine, and the variation in effectiveness and risk of side-effects tends to be much greater for newer, less-proven drugs. The picture gets even worse when you're talking about patients who are on multiple drugs, which can react with each other in any number of ways that are rarely well understood and often altogether unstudied. We don't get all this from the findings of most studies, because they tend to report averages, and are often presented in a way that make it sound as if a drug can do a lot for you, with only some chance of causing you problems. That may be sort of true, but there's really no way of getting around the fact that for most drugs you're rolling the dice to some extent as to whether the drug is going to help or hurt, if it does anything at all. There's hope genetic tests will eventually boost the odds further in your favor, but right now the claims you hear in the news that this is happening today is mostly hype, with just a few exceptions.
I want to make it clear I am in no way advocating pressuring your doctor to take you off any of your drugs--doctors admit in surveys to often succumbing to patient pressure on some drug decisions even if they don't think the decision is medically best for the patient--and I most certainly don't want anyone stopping drugs on their own. But there's no reason why you shouldn't ask your doctor to explain in more detail how likely a drug is to help, how likely it is to hurt, and why he thinks it's worth it. By the same token, you might want to know what applicable drugs she's decided aren't right for you, and why. Why shouldn't you be involved in a decision that essentially involves placing a bet on risks and benefits to your health? I always bow to my doctor's judgment, but she's willing to explain how she's arrived at it, and she's interested in getting my input when it's a matter of weighing the odds, as is usually the case with medications.
Sunday, June 27, 2010
Breakthrough School Anti-Obesity Study Proves...Little?
If you want a wonderful illustration of the paucity of clear information with which many and possibly most health studies provide us, and in particular how hard it is to wring any sort of credible insight out of weight-loss studies, look no further than the study currently making headlines by claiming that it proved the effectiveness of school programs designed to reduce obesity.
The USA Today report on the study kept it really simple: "The health interventions significantly lowered body mass index (BMI) in children in the 85th percentile or more. Overweight or obese kids in intervention schools were 21% less likely of being obese by the end of 8th grade. The program also lowered average levels of fasting insulin and the number of students with a waist at or over the 90th percentile in intervention schools."
But the HealthDay report provided some additional information: "....The program failed to reduce the overall numbers of overweight and obese schoolchildren--those numbers fell by 4 percent over three years whether the 42 middle schools in the study had such initiatives or not, the researchers report.... [and] children from both types of schools had the same average blood sugar levels and the same percentage of students with elevated blood sugar."
OK, so let's review: The interventions made a big difference with overweight kids--but didn't make the kids much less overweight. And the interventions reduced the risk of diabetes--but didn't prevent the high blood sugar levels that are the main indicator of diabetes or pre-diabetic conditions. Got that?
Here's what apparently happened. The schools that had the interventions saw their initially overweight kids become on average very slightly less overweight over the course of the study--just enough of a drop, it seems, to push many of them from being just heavy enough to be classified as overweight to just missing being heavy enough to be classified as overweight. Voila! Not much reduction in weight (compared to height) for the overweight kids, but a significant drop in the number of them that were "officially" overweight. The interventions did little or nothing to keep kids who weren't initially overweight from becoming overweight. And there was almost no difference between what happened in the schools that had the interventions and the schools that didn't--in both schools, there was a very slight drop over the course of the study in the kids' weight (compared to height).
As for the diabetes risk, the kids in the intervention schools saw slightly lower levels of insulin in their blood, which is generally associated with a lower diabetes risk. But it's a less important indicator than blood sugar levels, which weren't improved in the intervention schools. That's a great example of how scientific findings get muddled and often outright derailed by the choice of what gets measured in a study. (It's a problem I discuss at more length in an article in the July/August 2010 issue of Discover Magazine.)
Aside from the confusing and somewhat misleading way these results were presented in the press release, and made worse in some media accounts--it seems to me an honest presentation would have simply stated up front that the interventions didn't seem to offer any clear evidence that the interventions worked--there were complicating issues in the way the study was conducted. For one thing, the intervention schools not only made changes to the food available to the kids, but it also required longer and more intense physical activity. Yes, most of us (including me) believe these two factors go hand in hand when it comes to reducing obesity. But it may be that one of these factors has a much bigger effect than the other, and it is probably the case that some schools will find it much easier to implement only one, and not the other. So studies need to try to tease these two apart. But the bigger problem, I think, is that the schools that didn't get the official interventions were given money to make whatever changes they felt like making to their nutrition and fitness programs. Who knows what these schools did with the money? We don't even know what we're comparing here.
I certainly believe we have to come up with school-based approaches to reducing the astonishingly high child obesity rates, and I applaud any effort to study how that might be done. Unfortunately, this study's results seem to join the long train of obesity study findings that cast little light on the subject. Presenting the findings in a way that makes it sound as if a marvelous breakthrough was achieved only makes things worse.
The USA Today report on the study kept it really simple: "The health interventions significantly lowered body mass index (BMI) in children in the 85th percentile or more. Overweight or obese kids in intervention schools were 21% less likely of being obese by the end of 8th grade. The program also lowered average levels of fasting insulin and the number of students with a waist at or over the 90th percentile in intervention schools."
But the HealthDay report provided some additional information: "....The program failed to reduce the overall numbers of overweight and obese schoolchildren--those numbers fell by 4 percent over three years whether the 42 middle schools in the study had such initiatives or not, the researchers report.... [and] children from both types of schools had the same average blood sugar levels and the same percentage of students with elevated blood sugar."
OK, so let's review: The interventions made a big difference with overweight kids--but didn't make the kids much less overweight. And the interventions reduced the risk of diabetes--but didn't prevent the high blood sugar levels that are the main indicator of diabetes or pre-diabetic conditions. Got that?
Here's what apparently happened. The schools that had the interventions saw their initially overweight kids become on average very slightly less overweight over the course of the study--just enough of a drop, it seems, to push many of them from being just heavy enough to be classified as overweight to just missing being heavy enough to be classified as overweight. Voila! Not much reduction in weight (compared to height) for the overweight kids, but a significant drop in the number of them that were "officially" overweight. The interventions did little or nothing to keep kids who weren't initially overweight from becoming overweight. And there was almost no difference between what happened in the schools that had the interventions and the schools that didn't--in both schools, there was a very slight drop over the course of the study in the kids' weight (compared to height).
As for the diabetes risk, the kids in the intervention schools saw slightly lower levels of insulin in their blood, which is generally associated with a lower diabetes risk. But it's a less important indicator than blood sugar levels, which weren't improved in the intervention schools. That's a great example of how scientific findings get muddled and often outright derailed by the choice of what gets measured in a study. (It's a problem I discuss at more length in an article in the July/August 2010 issue of Discover Magazine.)
Aside from the confusing and somewhat misleading way these results were presented in the press release, and made worse in some media accounts--it seems to me an honest presentation would have simply stated up front that the interventions didn't seem to offer any clear evidence that the interventions worked--there were complicating issues in the way the study was conducted. For one thing, the intervention schools not only made changes to the food available to the kids, but it also required longer and more intense physical activity. Yes, most of us (including me) believe these two factors go hand in hand when it comes to reducing obesity. But it may be that one of these factors has a much bigger effect than the other, and it is probably the case that some schools will find it much easier to implement only one, and not the other. So studies need to try to tease these two apart. But the bigger problem, I think, is that the schools that didn't get the official interventions were given money to make whatever changes they felt like making to their nutrition and fitness programs. Who knows what these schools did with the money? We don't even know what we're comparing here.
I certainly believe we have to come up with school-based approaches to reducing the astonishingly high child obesity rates, and I applaud any effort to study how that might be done. Unfortunately, this study's results seem to join the long train of obesity study findings that cast little light on the subject. Presenting the findings in a way that makes it sound as if a marvelous breakthrough was achieved only makes things worse.