Medical Management of Marfan Syndrome
15:58-23:40
So, so next I just want to change topic before we come on to the, the, the, the real substance of what I want to talk about but I just want to make sure everyone's on the same page with understanding what a randomized controlled trial is. Some people, some of you are going to know all this already, some people maybe not, so I just want to make sure everyone's clear about it.
ウェビナーの本題に入る前にランダム化比較試験について説明したいと思います。既にご存知の方もいらっしゃるかもしれませんが、皆さんに理解していただきたい内容です。
So in a randomized control, some of you will have been in randomized control trials I know, so the idea of a randomized control trial, it hasn't, you know, it hasn't been around for the whole of human history. This, this concept was invented in the 1950s. It's a British invention, I should say.
ランダム化比較試験の歴史はそれほど長くなく、考案されたのは1950年代のイギリスです。
And the idea was that you, you take participants who, who have got the disease that you want to study, let's say, patients with Marfan syndrome and then you want to test whether the treatment works compared to no treatment and so what you do is you randomly allocate, let's say, half the the patients to having the intervention that you want to test, let's say, the medication and the other half of the patients are randomly allocated to not getting the treatment and this idea that the treatment allocation had to be at random was not obvious to human beings until really about the 1980s and it's kind of amazing that this hadn't really become clear but until the 1980s.
基本的には、治療する患者さんと治療しない患者さんとで結果に違いが出るかどうかを調べる試験なのですが、患者さんをどちらかのグループにランダムに（無作為に）割り当てることがポイントになります。例えば、マルファン症候群の患者さんを薬物治療を行うグループと薬物治療を行わないグループにランダムに分けるということです。この「ランダムに分ける」ということが1980年代までは自明なことではありませんでした。
It was extremely common for people not to be allocated at random and what would happen is the doctors would decide which group you would go into and you would think, well and the doctors used to, who did these trials before the 1980s, used to really think that they could decide in an unbiased way but they really, really couldn't and we, we have learned the hard way that, that if you want to get an unbiased group, in other words, if you want the the people getting the, the, the treatment group and, the and, the and, the control group to be similar in terms of their composition you, you must randomly allocate people and so if you ever see a trial a study that's reporting to show that a medication works and there's no randomization there is no random allocation of people to, to treatment or no treatment or to different treatment arms then alarm bells should be ringing and is, you know, one has to treat that with significant amount of skepticism.
1980年代以前は担当医が割り当てを決めることがごく一般的であり、医師本人も公平な割り当てが可能だと思っていたのですが、実際はそうではありませんでした。そこから数々の紆余曲折を経て、同等の属性を持つ、治療群と対照群（治療を受けないグループ）に分けるためにはランダムな割り当てが必要であるという結論に至ったのです。そのため、薬の効果が示されたと主張する臨床試験があったとしても、ランダム化（治療群と非治療群あるいは別の治療を行った群への無作為な患者の割り当て）が行われていないのであれば、疑いの目で見なければならないということです。
And then what usually happens and what happened in the trials of the treatments that I'm going to show you is that measurements were taken of people's aortas at the beginning of the trial and then they continued to take measurements throughout the trial and then they took a final measurement at the end of the trial and so for each patient it was possible to see how that patient aorta was behaving over the course of the trial and, and, and then you could work out whether the patient aorta was growing and if it was growing how fast it was growing and that's how the trials of, of, of Marfan syndrome were conduct, in Marfan syndrome were conducted, so that's, that's how these trials were, were done.
ちなみに、後ほど紹介するマルファン症候群の薬物治療に関する研究では、臨床試験のはじめ、臨床試験中、臨床試験の終わりに大動脈のサイズを計測し、大動脈の拡張の程度や拡張速度といった、それぞれの患者さんの大動脈の経過を調べました。
Now we have in the, in, in, in, the sphere of what's called evidence-based medicine, which is the way in which we you try to apply evidence and, and science to patient care. This kind of pyramid of a hierarchy of, of evidence.
次のスライドには、いわゆるEBM（エビデンスに基づく医療）におけるエビデンスに沿った階層構造が描かれています。EBMでは、エビデンスに基づく治療法が適用されます。
And so in, in the, in the past we used to very heavily on experts opinions, so, you know, a professor or a specialist would say, "this is what I think we should do," and it nowadays we put that really at the bottom of of the hierarchy because we've realized that experts got it wrong a lot and, you know, it was very much biased by what the, you know, sort of loudest voice in the room was the most, you know, sort of, sort of most outspoken person sort of felt.
かつての治療は、専門家の意見に大きく依存していました。教授などの専門家が「こうすべき」と言えば、その意見に従っていたわけですが、今では、専門家の意見はピラミッドの最下層に置かれます。というのも、専門家にも多くの思い込みがあったり、カンファレンスで一番声が大きな人の意見に治療方針が大きく左右されるといったことがあったためです。
And then over time, you know, ideas tend to get tested in various kinds of studies and then here we have these kind of non-randomized trials where there was, medications were being systematically tested but without randomization and then there was a feeling that randomized controlled trials were probably better.
時間経過とともに、エビデンスに関する様々な研究がなされた結果、非ランダム化試験というものが登場しました。この試験によって、薬の系統的試験が可能になりましたが、ランダム化は行われませんでした。その後にランダム化比較試験が考案され、より優れた試験であるとの印象が持たれるようになりました。
But then it, we had a situation in which often people would do random, several different randomized control trials. Maybe there'd be a randomized control trial in France, there'd be a randomized control trial in Spain, there'd be a randomized control trial in Canada, then there'd be one in the US and sometimes they would all say the same thing. Well, that's pretty easy and sometimes they would say slightly conflicting things because they tested things in slightly different ways, maybe they'd slightly different medications, maybe the populations they were studying was slightly different and the, then there would be various different ways of looking at overviews of these trials and sometimes experts would get together and say what they thought were the best ways of doing these trials.
やがて、複数の国々でいくつかの異なるランダム化比較試験が行われるようになりました。これらの試験結果が同じであれば問題はないのですが、試験方法や試験対象の薬、対象集団のわずかな違いなどで、相反する結果が出ることがあります。すると、これらのランダム化比較試験全体の捉え方にも多様性が生まれます。専門家らが集まって、自分たちが考える試験方法が最善であると結論することもあります。
But finally people developed systematic ways of putting trials together and there is a special way of putting trials together that is called the meta-analysis and the, the, the correct way of doing a meta-analysis is to bring together the trials and this is clever bit is that you add, you, you essentially add together the information in all those trials and you weight the trials according to the amount of information that is contained within each trial.
しかしついに、これらの試験を統合して体系的に捉える方法が考案されました。それがメタアナリシスです。メタアナリシスの正しいやり方は、臨床試験を集めて、これらに含まれる情報を合算し、各試験に含まれる情報量に応じて各試験の重み付けをするということです。
Now that is very, very misunderstood and if you understand that what I just said you know more about meta-analysis than most doctors, okay? Meta-analysis has a slightly bad reputation, particularly in the US, I should say, because there are lots of differences, for two reasons: one, most doctors don't understand that sentence that I just said and number two, because there's lots of ways of doing meta-analysis wrong and there's only really one way of doing them right, okay? but if you, if you avoid those two errors you understand what meta-analysis done correctly really is. It is putting together trials in a logical way in which the information, in which the trials are weighted according to the amount of information that each trial contains and that you do the analysis correctly and you don't make the mistakes that are easy to make then the meta-analysis is the best way of making the correct judgments about the the way in which one should proceed. That's the concept, okay, well, that, that's that's my belief anyway, okay.
メタアナリシスは誤って理解されることが極めて多いのですが、私が先ほど申し上げたことを理解していただけたのであれば、大部分の医師よりもこの評価方法について多くを理解していると言えます。メタアナリシスは、特に米国では、あまり評判が良くありません。間違った実施方法が多く存在しているからなのですが、その理由は二つあります。一つ目としては、大半の医師が先ほど申し上げたことを理解していないということです。二つ目は、メタアナリシスの正しい実施方法はただ一つであるのに対し、誤った方法は山ほど存在しているということです。繰り返しますが、メタアナリシスのやり方は、臨床試験を論理的に統合したうえで、それぞれの試験に含まれる情報量に応じて重み付けするということです。正しく、かつ陥りがちなミスをすることなく実施できるのであれば、メタアナリシスは、正しい判断を下すための最良の方法であると考えられます。
The Marfan Foundation did not participate in the translation of these materials and does not in any way endorse them. If you are interested in this topic, please refer to our website, Marfan.org, for materials approved by our Professional Advisory Board.
The Marfan Foundation は、当翻訳には関与しておらず、翻訳内容に関してはいかなる承認も行っておりません。このトピックに興味をお持ちの方は、Marfan.org にアクセスし、当協会の専門家から成る諮問委員会が承認した内容をご参照ください。
