The Futile Cycle

There’s nothing quite as nightmarish an experience as driving in downtown Boston at night with confusing directions and under a time limit.

This image resizing technique really blows my mind, and yet it’s so simple and clever a concept.

I think that half the problems of the US tort system come from the fact that the US didn’t grow up learning from Oscar Wilde that the appropriate response to a slap in the face is a devestatingly witty comeback, and lacking that, one would just walk away with pride tucked between the legs. For our ignorance, we get nuisance lawsuits for slander and libel. My sympathies to PZ Myers.

I’m not sure when exactly they did so, but Nature has changed its website to a much more web 2.0-y look. They’ve started to really highlight a lot of their new internet initiatives, including Connotea, Precedings, and their Networks and Blogs. I’m a big fan of science journals actually embracing this whole internet thing that’s been here for around 15 years, rather than simply using it as a way to get subscriptions to PDFs. Nature’s been doing this a lot.

But I don’t like their redesign that much. It’s kinda cluttered — much less so than before, I’ll give them that — but still quite so, which is the opposite of what a journal should be.

I found this figure in a review paper that I’m reading (MV Rockman and L. Krulgyak (2006), Nat Rev Genet, 7, 862-72), and I think it’s awesome. More papers need figures like this.

Clifford J. Rosen has written a perspective in the New England Journal of Medicine summarizing his views on the FDA Advisory meeting on rosiglitazone (a.k.a. Avandia), which he was chair of.

I agree with his main conclusion, that rosiglitazone is probably not as good as some alternatives, but I have to say, his article’s stance on observational studies and meta-analyses was rather poorly presented. The main data he cites for showing that pioglitazone is better than rosiglitazone for cardiovascular risk is Gerrits et al., basically an observational meta-analysis. On the other hand, he essentially seems to dismiss the observaitional studies by Wellpoint, a health care insurer, which was much larger. I’m giving him the benefit of the doubt that he’s being self-consistent, but the way the article is written wrongly portrays his references. Consider that he says,

Moreover, we are facing a troubling paradox: preliminary data that were presented at the meeting and published by Gerrits et al. suggest that among the thiazolidinediones — a class of drugs that has been shown to improve metabolic control — rosiglitazone may increase cardiovascular risk whereas pioglitazone may reduce it.

Later on, when he mentions the Wellpoint study, he concludes,

The contrasts among the levels of evidence and the results regarding the safety of rosiglitazone raised new questions about relative and absolute risks but also highlighted the weaknesses of observational studies examining events that are common and whose rates are likely to be increased only slightly by a given drug, even in a large cohort (such as that used by WellPoint, which comprised 160,000 patient records).

Note that he never mentions that the Gerrits study is essentially an observational study, too, comprised of data pulled from a large health care insurer. So, the way he wrote the article casts a falsely bad impression on the studies showing little increase in cardiovascular risk for rosiglitazone compared to the alternatives, while not casting the same sort of critical eye at the studies that seem to support his conclusions.

A better (and I find, more convincing) argument would have been that pioglitazone has been demonstrated, in a clinical trial, to have fewer cardiovascular events than placebo, whereas rosiglitazone has not been shown conclusively to have less or more. So, if faced with a choice, it’s easy to recommend pioglitazone over rosiglitazone.

That argument would be much clearer than what he did, which was to simply cite a whole slough of meta-analyses and observational studies (the only non-meta-analysis data he cites at all are two clinical trials, both basically mum on cardiovascular risk), cast doubt on some of them, and then leave the reader to weigh one against the other while making the (unwarrented) conclusion that “a new ‘wonder drug,’ approved prematurely and for the wrong reasons by a weakened and underfunded government agency subjected to pressure from industry, had caused undue harm to patients.” Weighing meta-analyses that conflict with each other is for Ph.D. level statisticians, and I (nor, do I think, most of the readers of the NEJM) am not up to it. I’m still not terribly convinced that rosiglitazone has absolutely hurt patients; I think it’s premature to say so (otherwise, why not pull it from the market?), but certainly there are much more effective alternatives. Clifford Rosen just didn’t make a good case for it.

The Perseids meteor showers are happening tonight, from around 10 PM (August 12) to dawn (August 13), concurrent with a new moon (which makes them easier to see). Unfortunately, I can’t get to a rural area, but my part of town is a little darker, so I hope to see something!

Some blogs which I’ve finally gotten around to adding to the blogroll: Mystery Rays from Outer Space, which is a great immunology blog by a professor from Michigan State; A Blog Around the Clock, a rather famous blog about pretty much anything, though Bora does have an expertise in chronobiology and a keen interest in Open Access science; The Evilutionary Biologist, who is evil evil evil, but also quite a nice blogger on evolutionary biology (I especially like his weekly citation classics; find the latest one here); and The Loom, by Carl Zimmer, who is quite awesome. I’ve been reading Carl ever since he migrated over from Corante’s blog universe, and his Parasite Rex book is quite fun.

Check them out, they’re all great!

In the latest entry into the whole Avandia (a.k.a. rosiglitazone) deal, yet another meta-analysis published in the Annals of Internal Medicine shows no statistically significant increase in cardiovascular risk from Avandia, further giving weight to the quote from Ernest Rutherford, “if your experiment needs statistics, you ought to have done a better experiment.” Or weight to any number of other quotes, including Mark Twain’s, “there are three kinds of lies: lies, damned lies, and statistics.”

So, in conclusion, drugs have side effects, sometimes which are risky. (oooh.) Maybe Avandia has some, too, but no one knows. All Steve Nissen’s study shows is that we should conduct a clinical trial specifically to address this issue before making any more definitive conclusions.

Hopefully, I will never have to touch Microsoft Word ever again, thanks to Apple. The new version of their word-processing and page layout program, “Pages”, finally has a “change tracking” feature, which is apparently compatable with Microsoft Word’s Track Changes. This was really the last reason for me to use Word, which I’ve avoided as much as I can with LaTeX. Word was slow, buggy, and not native to Intel Macs (making them even slower). It was also kind of a pain to use. Now that I can do the editing in Pages, I don’t have any need for Word, other than to open the occasional file sent to me. But that’s what PDFs are for, right?