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.

4 thoughts on “The Trouble with Medications

  1. Anonymous says:

    Always curious as to how people get started weiting this much giving their opinion about other opinions.What is there to sugest the author is better informed or more intelligent th those he questions.It smacks a lot like the current media method of attempting to stir interest or curiosity through the use of words such as: could, might, some say, reported, etc. as opposed to confining themselves to fact. The use of half truth and innuendo is so prevalent we have personal and world wide acceptance of "where there is smoke there is fire" resulting in assumption and belief in totally erroneous actions involving virtually every phase of life. Some and substance: exactly the sort of piece that should be ignored and considered to be the result of another over educated individual who has chosen a path other than actually working on behalf of producing useful goods or services.

  2. Just think of the future. "Personalized Medicine."Pharmaceutical companies can find some narrow group of people for whom a drug "works" and get it on the market and then let their sales people promote it off label.Not that any have done anything like this in the past.

  3. You've put your finger on a real potential problem, Edward. "Personalized medicine" is usually hyped as meaning we will each get exactly the drugs that work best on us, but to the extent that personalized medicine has worked at all so far–there are very few examples in spite of 20 years and countless billions spent on studying the genome, and the few examples aren't very impressive–it usually means identifying that small minority of people for whom a certain drug has much of a chance of helping at all. But what will happen when the rest of us are told our cancer or heart disease is less likely to be helped by a drug that's helping others? It's mostly insurance companies who will push for this sort of personalization. The rest of us want a shot at a drug working, even if it almost certainly won't, and doctors are often loath to withhold treatments from desperate patients. Not a pretty situation.

  4. Anonymous says:

    @Anonymous did have a misspelled point. This blog focuses on why I should not believe studies and then turns around and says, BUT you should believe these studies. You can't have it both ways. Secondly, it is curious that most blogs who buy into the unprovable social medicine theory of "medicalization" often ignore the very real dangers of non-pharmaceutical treatments. This may be because they jumped on a bandwagon without checking to see what the actual agenda is.If you take a leaf from the be skeptical of all studies page then it isn't just artificial interventions that can be risky. Very few studies look at the risks associated with say behavioral treatments and even fewer journalists walk their talk when it comes to such areas. Perhaps Mr. Freedman is an exception. I haven't read all his posts.

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