I’m back at last. I have spent the last few days helping to get my mother buried, in our hearts if not in fact, and only now have time to finish up.
In this post I’ll address the arguments made by David Felson as to the efficacy of glucosamine and chondroitin. Dr. Felson focused mostly on glucosamine for which there is more evidence. His argument was in three parts: he taught us about effect sizes as a way to compare studies; he talked about the GAIT study and issues of subgroup analysis; and he reviewed a meta-analysis done by him and his fellow, Steven Vlad.
Part 4a: Effect Sizes
First, he introduced the concept of the effect size. This is a way of standardizing the results of trials so that they are more directly comparable. It is defined as the difference between outcomes between to trial arms, divided by the standard deviation. It therefore gives the difference in outcome standardized to a normal distribution: a change of 1 represents an improvement of 1 standard deviation for treatment over placebo. This is a large effect of any therapy. An effect size of 0.2 is a small effect, 0.5 a modest effect, and 0.8 a large effect. For comparison, treatment of knee OA with NSAIDs gives an effect size on the order of 0.2-0.3. A total knee replacement – definitive therapy for knee OA – gives an effect size of 1 or greater. Glucosamine has been claimed to have an effect size on the order of 0.3-0.8 depending on the study you read; at least as good and maybe better than NSAIDs. Some studies have shown effect sizes larger than 1 – on the order of magnitude of a knee replacement. Dr. Felson finds this to be simply impossible to believe and I agree.
As you may have noticed, I’ve had to take a couple of breaks presenting this final 2006 ACR session, and have divided it up amongst a few posts over a few days. There are reasons for this. 1) As I expalined earlier, it is a subject that is near and dear to my heart and so I’m going into detail. 2) These products are widely available and widely used and the debate about their effectiveness deserves some space. 3) I just don’t have the time for sustained writing right now. There are just too many other things going on.
But I’ll try to post part 4 tomorrow or maybe the next day, so please stay tuned. I also want to sum up the conference as a whole. I’ll get there!
Part 3 (See here for parts 1 and 2)
Dr. Theodosakis then took the podium to present the case for glucosamine and chondroitin. Let me first say that Dr. T. is a young, charismatic man and appears to be a very nice guy. He is certainly an engaging speaker and certainly believes everything he says. I very much doubt that he supports G/CS’s use just because he may have a financial interest; I think he truly believes that these are effective products. That does not mean that I agree with everything that he said.
He went through a lot of information very quickly, but he provided copies of all his slides in his syllabus and encouraged us to review these for details of his argument. I write this with
One of the first things he talked about was our obligation as physicians to ‘first, do no harm’. If you don’t know this already, this is from the Hypocratic Oath that almost all physicians take when they get their MD. I agree that this is a very important principal; his point in bringing it up here is to point out G/CS have excellent side effect profiles. Unlike almost every drug we use, they really have no known side effects. Many of the medications we routinely use certainly do. NSAIDs (non-steoidal anti-inflammatory drugs) for instance (like ibuprofen and naproxen) are well known to have the potential to cause GI bleeding. Acetaminophen (Tylenol) can cause liver failure, and actually is one of the most used medications in attempted suicides. G/CS has never caused a death that we know of.
This was the last session I attended and concerns a topic of great interest to me, so I’m glad I was able to attend. I expect that this is going to turn into a long post, because it concerns some issues which are close to my heart and that’s I’d like to explore in a little detail.
At issue is whether glucosamine and chondroitin are effective in treating osteoarthritis (OA), especially OA of the knee which is the most common site that OA hits. There are two separate issues here: 1) whether they help pain; and 2) whether they help slow or stop the progression of the disease. The rheumatology community is remarkably divided on this issue. Many think glucosamine/chondroitin are probably quite effective and recommend them to their patients, while others think that they are not at all effective. Hence the goal of this session was to present the evidence for both sides and to try to let the rheumatology community decide for themselves. I’m not sure if it was effective in this. It would be interesting to see whether any practitioners actually changed their minds about G/CS utility, or whether those who were unsure finally came down on one side or the other. (Hmm … that might be an interesting study …)
The abstracts I saw presented today tended to have a common theme: they all looked at the risks of therapy with medications we use frequently. You might think that figuring out whether a medication or group of medications cause, say, cancer would just be a matter of following some people and seeing whether they develop the disease. Unfortunately it’s a lot more complicated than that for a few reasons.
For a start, you have to follow A LOT of people for a long time to detect some diseases. When a cancer only occurs in, say, 1 out of 1000 people at baseline over a period of 10 years, you can see that you have to follow a lot of people to see whether it occurs more often in a group of drug users. Seeing 2 out of 1000 people come down with it is a doubling or the risk, so it sounds like that should be straightforward, but how often can you really follow 1000 people for 10 years. And remember, you really have to follow 2000 people because you really also have to follow a group of non-drug users to get real estimates fo the difference in risk: using an historical group of non-drug users isn’t really a good way to do it.
And then, is there really a difference between 1 in 1000 and 2 in 1000? It’s a doubling of risk, but is it just chance – after all it’s only one extra person in a thousand.
Well, actually I’m heading to my parents’. I’ll get back home sometime this weekend.
But it was my 5th day at the ACR Conference, the 3rd day of the conference proper. I managed to get to two sessions before I had to head to the airport, and they were two good ones. The other thing I wanted to talk about in this post were the poster sessions.
Think of your favorite football field. Now put a bunch of freestanding bulletin boards in rows all the way down it so that it fills up- leave about12 feet between rows so people can get through them easily. Now cover the boards with posters of about 3 X 5 feet. That’s what the poster sessions are like.
I went to another session that was supposed to help young investigators get a research career established, but I’m not going to talk about it at all. I will talk quickly about the epidemiology abstract session though.
Dr. Kwoh confirmed something that has been suspected for a while now; namely that African Americans think differently about health care. In this case, he found that A-As are more unlikely to consider hip replacement even if it is indicated. Many of them simply distrust the medical system.
I again hit the plenary session today. I’m only going to talk about one of the abstracts presented, and that’s the last one by Dr. Englund. He looked a knee MRIs in a community population and found that tears or maceration (destruction) of the meniscus – the ‘padding’ of the knee joint, if you will – are common. Something like 1 in 4 knees had meniscal injuries, and the prevalence was something like 50% in people over 55 (I’ve got the numbers wrong, but it’s something like that). Meniscal injury was associated with osteoarthritis (OA) – not surprising really. If the joint is narrow and ratty, then maybe it causes meniscal damage. On the other hand, maybe the meniscal damage causes OA.
But what was very interesting, is that after controlling for OA, there was no association of pain with meniscal injury. This flies in the face of current thinking by most orthopedic surgeons who often assume that a meniscal tear must be causing pain. Therefore they do surgery to repair or remove it. We know that this can accelerate osteoarthritis, but it’s justified because it’s assumed the meniscal damage causes pain. Dr. Englund’s study strongly suggests that that’s not the case, and that meniscal damage is very common – and therefore will be found in lots of patients if you look for it – but is probably NOT causing significant pain. Therefore, operating on meniscal tears may not only be unnecessary but, because removing the meniscus can accelerate OA, may actually be harmful.
This is a very important result and may change how we manage patients with meniscal injuries in the future. It also means that we probably shouldn’t think too much of an MRI that shows damage.