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.
Thursday, July 1, 2010
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.