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Sunday, June 10, 2007

The Life and Times of Martin B Keller, MD - Part I

The Life and Times of Martin B Keller, MD - Part I

Matthew Holford

I'm really quite excited about this, to be honest, because this is the first time that I've actually written "to order", as it were - I usually "go into one" on a subject of my choosing, which I rather suspect is a much more straight forward business. However, Bob asked me if I'd take a stab (I thought twice, before deciding to include that turn of phrase) at writing something on Dr Keller, who is one of those "key opinion shapers" that we've all heard about. I wonder how one learns to shape opinions?

Anyway, in the field of Seroxat, and related matters, Dr Keller's name is mud (and second only to Dr Alistair "Ali B" Benbow), amongst patients who have suffered side effects, and amongst the families of children, particularly, who have committed suicide, whilst on the drug. The story is an old one, but very briefly, Dr Keller put his name to a piece of analysis, which was later revealed to have been written by a PR firm. This piece, which reviewed the infamous Trial 329, was published in July, 2001; a full two and half years after the equally infamous October, 1998, memo was circulating, inside SmithKline Beecham (later merging with Glaxo Wellcome, to form Glaxo Smithkline), which declared that the drug was a pile of crap, and was dangerous, to boot (I paraphrase, naturally). The story goes that SKB realized that it had a turkey, but decided to dress it up, in order to get it licensed, hence the need to get the thing into a peer-reviewed journal. Now, this piece of analysis, which Dr Keller "wrote", concluded that Seroxat was "generally well tolerated and effective for major depression in adolescents." Unlike the memo which said (and I paraphrase) "it's a pile of kak."

"Effective", in this context, means that patients achieved an improvement of 8 points, or better, on the Hamilton DRS (a 66-point (? I always get a different total, each time I add up the maximum possible score!) rating scale, to assess the severity of depression), if I read the guff correctly. However, it seems that Seroxat was only marginally better than placebo, if at all. I don't think it's necessary to go into detail as to the way that adverse events were discussed, in Dr Keller's report, although he did comment afterwards that none of those suffering suicidal ideations actually went on to top themselves. Suffice is to say that, in December, 2003, the MHRA declared the drug too risky to be granted a marketing authorization (although it may still be prescribed "off-label", I understand, if your quack feels that it's appropriate - I asked the MHRA about this, but it wouldn't confirm what the status was (please see Rants passim, for my view of the MHRA)). I think it was in October, 2002, that the US regulator, the FDA, issued an advisory to physicians that the trials had indicated that the drug was only as effective as placebo. And so on, and so on. I wrote to Marty Keller, recently, to ask him if his view of paroxetine (generic name) had changed, in the intervening years. He hasn't written back, yet, but you never know.

Now, I like to think of myself as a reasonable man. Besides which, I wouldn't like to lay myself open to a libel action, so I thought I'd write a little biography, just to give him a fair hearing, based on what was available in the public domain. I'll also be sending him a copy, so if he wishes to correct me, I will be sure to adjust the text in accordance with his instructions - unless I am able to validate the thing he disagrees with, and that looks more plausible, in context (I do hate to interrupt the flow of a good story, don't you?).

Anyway, I'm a lazy bastard, so the first thing I did, by way of research, was to visit the Brown Medical School website. Brown being the august establishment where Dr Keller is Professor and Chairman of the Department of Psychiatry and Human Behaviour. Good Lord, would you believe that his CV runs to no less than 61 pages? What a lot of Boards he sits on! What a lot of learned stuff he's written! What a lot of important posts he's occupied! What a lot of honours he's received! This, then, is how one becomes an opinion shaper: one sits, writes, occupies and receives. Now, if I wasn't so lazy, I'd actually read some of the 320 articles that he's written (at least, I assume that he's written them), or the 36 books and journal articles that he's contributed to. That is, of course, if I wasn't so ill-educated such that his learned writings would be quite beyond the scope of my limited understanding.

But that's for another day (or Part II, as it will be known). I'm not quite sure when Dr Keller was born, but he was at Dartmouth College in 1968, when I imagine he would have been in his late teens, so I'm going to guess that he was born in the late 40s, or early 50s. Let's say 1950, just for the sake of argument. Do you know what was going on in the world, in 1950? I didn't. So I checked it out, because I think it's important that we understand as much as we can about the environment in which Dr Keller spent his formative years, given that there is not really that much personal information about the good doctor available on the net. Not that I could locate, in a 10-minute scan of the Google search that I did on Dr Keller's name, in any case.

The UK recognized the People's Republic of China, and China told the UK to fuck off. The Cold War was just kicking off, with Truman ordering the development of the H-Bomb, in response to the Soviets' first Atom Bomb test. Einstein warned us that a nuclear war could lead to mutual destruction (astonishing that he found the need to state that, but there you go). The first VW Microbus rolled off the production line. Apartheid was introduced in Suid Afrika. The UK recognized Israel, and Israel apparently didn't tell the UK to fuck off. The Korean War started. The US defeated England 1-0 in the 1950 World Cup (I toyed with the idea of leaving that out, but you can't change history, can you?). Communist sympathisers were rioting in Paris and Berlin. Peanuts was published, for the first time. Oh, you get the idea, don't you: it was all a long time ago, and everything's changed, since then?

Anyway, that's just a little bit of background. I've decided that I'm going to teach myself how to be a psychiatrist, and I'm going to do this by learning from one of the best: Dr Marty Keller. I'll read a few of his early publications, and try to get to grips with the jargon, because it's always useful, to have another language. For my next trick, I will try to translate these into everyday english.

Watch this space, as they probably don't say, very often.

Copyright Matthew Holford, 2007