A couple of weeks ago I was part of the “promotiecommissie” of RvA at the university of Leiden. This is the committee that evaluates the thesis of a PhD candidate, and which then subsequently is also part of the opposition during the in-person defense, sometimes known as the “viva“.
I was quite impressed by the work described in the thesis. Not just because the individual projects described in each chapter was solid, but also how one clinical problem was approached from several angles with each research question answered with a different methodology. But every chapter it was clear that it contributed to the central theme: is the current practice of venous thrombosis prophylaxis in certain orthopedic patients justified.
The candidate started out with a description of risk factors of venous thrombosis related to tho either lower leg cast immobilization or arthroscopy of the knee and thus establishing that indeed there is an increased risk and that certain risk factors contribute to this risk. A survey amongst colleagues subsequently showed that the prophylactic treatment given to these patients differs quite substantially. This relatively simple element of the thesis is crucial, as it shows equipoise for the treatment – even though there is some evidence from trials, the evidence is weak and methodological unsound (they mostly use ultrasound diagnosed venous thrombosis, not a clinical diagnosis) resulting in highly varied practices.
So the stage is set for a trial. In fact, two trials, one for each of the two patient groups is presented in Chapters 5 and 6 of the thesis. Impressive stuff, which found its way into the NEJM, which showed that treatment with LMWH is in fact not better than placebo. Given this result, this is normally the end of it, but “compared to placebo” should normally raise some eyebrows. Is that the right comparison group? In this case, you can argue that it is, but even if you don’t think so, just go to chapter 7, wherein another group at high risk of venous thrombosis a comparison with compression stockings is made – again, here no evidence that LMWH is better. The candidate here presented this is an IV-analyses. Interesting thought, but I disagreed – the idea behind the comparison between centers has some IV elements in it in the rationalization, but there is no actual IV-analysis being done. Potato, Potato perhaps, but hey, it is a PhD defense! The last two chapters were the first step to a prediction model for venous thrombosis in orthopedic patients (prediction in case-control design, no validation). The idea behind is that if you can identify among all patients the high-risk group, treatment with LMWH might still be useful.
But for now, the evidence is clear – no LMWH in these orthopedic patients for the prevention of venous thrombosis. And that brings me to the lesson that I took from this thesis – it is possible, and necessary, that we evaluate medical practices already in place. It is the whole premise behind the book “Ending medical reversal”. I got that book as a gift from a colleague in Berlin, but I never got around to start. But after reading this thesis, I grabbed the book and read it cover to cover in just two days. Easy read, and interesting ideas, on how medical reversals, its causes, and how to prevent them from happening in the future. Some of my questions during the defense were even based on the book – for example, whether a cluster-randomized trial design should not be the golden standard in medical reversal research.
But the bottom line of the book+thesis combo is clear: there are a lot of medical practices used on a daily basis that should be re-evaluated. Except for one: “LMWH for the prevention of venous thrombosis in all patients with below the knee immobilization or arthroscopy” can be taken off the list.
The full text of the thesis can be found here.