So I'm a doctor, but I kind of slipped sideways into research, and now I'm an epidemiologist. And nobody really knows what epidemiology is. Epidemiology is the science of how we know in the real world if something is good for you or bad for you. And it's best understood through example as the science of those crazy, wacky newspaper headlines. And these are just some of the examples.
我是名医生,又另起炉灶做研究 如今我是名流行病学家 没有人真正知道什么是流行病学 流行病学是了解现实世界里 某种东西对我们是有益还是有害的科学 了解它最好的方法就是例子了 特别是那些疯狂古怪的报纸头条 这里有几个例子
These are from the Daily Mail. Every country in the world has a newspaper like this. It has this bizarre, ongoing philosophical project of dividing all the inanimate objects in the world into the ones that either cause or prevent cancer. Here are some of the things they said cause cancer: divorce, Wi-Fi, toiletries and coffee. Some things they say prevent cancer: crusts, red pepper, licorice and coffee. So you can see there are contradictions. Coffee both causes and prevents cancer. As you start to read on, you can see that maybe there's some political valence behind some of this. For women, housework prevents breast cancer, but for men, shopping could make you impotent.
首先来看每日邮报。每个国家都有像这样的报纸 它们的一项长期而古怪的哲学使命就是 把这世上所有的事物 分成致癌和防癌两类 这些是最近发布的致癌的东西: 离婚,无线网,梳妆用品还有咖啡 这些是防癌的: 面包皮,红辣椒,甘草和咖啡 你已经发现了自相矛盾之处 咖啡既致癌又防癌 如果继续读下去 你会开始怀疑这类报道是否别有用心 “女人们,做家务能预防乳腺癌” “购物可能导致男人性无能” 那么我们就要
(Laughter)
So we know that we need to start unpicking the science behind this. And what I hope to show is that unpicking the evidence behind dodgy claims isn't a kind of nasty, carping activity; it's socially useful. But it's also an extremely valuable explanatory tool, because real science is about critically appraising the evidence for somebody else's position. That's what happens in academic journals, it's what happens at academic conferences -- the Q&A session after a postdoc presents data is often a bloodbath. And nobody minds that; we actively welcome it. It's like a consenting intellectual S&M activity.
揭开这些说法一看究竟 我要说明的观点是 揭穿骗人的说法 以及它们背后的证据 这不是卑鄙的吹毛求疵行为 这是对社会有用的 也是极有价值的 阐述工具 因为真正的科学 是批判性地评估他人提出的论据 这是就学术期刊的评审方法 也是学术会议上的常事 会场发言完毕后的提问环节 常常是场血战 没人会介意,我们反而十分欢迎 就像是自愿的智力上的SM一样
(Laughter)
我将展示给你们的
So what I'm going to show you is all of the main things, all of the main features of my discipline, evidence-based medicine. And I will talk you through all of these and demonstrate how they work, exclusively using examples of people getting stuff wrong.
东西是 我研究领域和核心内容和特色- 循证医学 我将给各位讲解 并展示那些出了纰漏的例子 是如何欺骗大众的
We'll start with the absolute weakest form of evidence known to man, and that is authority. In science, we don't care how many letters you have after your name -- we want to know what your reasons are for believing something. How do you know that something is good for us or bad for us? But we're also unimpressed by authority because it's so easy to contrive. This is somebody called Dr. Gillian McKeith, PhD, or, to give her full medical title, Gillian McKeith.
首先是最不堪一击的证据来源 权威人士 在科学面前,你名字后面有多少头衔并不重要 我们在乎的是你确信某事的原因是什么 你是怎么知道什么对我们有益 什么又有害? 不过我们早就对权威不感冒了 因为如今权威的身份太容易伪造 这是个叫Gillian McKeith的博士(医生?) 加上她的医学头衔嘛,也就是Gillian McKeith
(Laughter)
(笑声)
Again, every country has somebody like this. She is our TV diet guru. She has five series of prime-time television, giving out very lavish and exotic health advice. She, it turns out, has a non-accredited correspondence course PhD from somewhere in America. She also boasts that she's a certified professional member of the American Association of Nutritional Consultants, which sounds very glamorous; you get a certificate. This one belongs to my dead cat, Hettie. She was a horrible cat. You go to the website, fill out the form, give them $60, it arrives in the post. That's not the only reason we think this person is an idiot. She also says things like eat lots of dark green leaves, they contain chlorophyll and really oxygenate your blood. And anybody who's done school biology remembers that chlorophyll and chloroplasts only make oxygen in sunlight, and it's quite dark in your bowels after you've eaten spinach.
每个国家都有这样一个人 她是电视饮食节目大师 上五个黄金档的系列节目 放出丰富又充满异域风情的保健意见 结果发现她的学历是不知美国哪儿的 一个不可信的函授博士 她还吹牛说她是美国营养咨询师协会的 持证专业人员 这听起来大有来头 一张证书就能解决一切 这是我死掉的猫Hetti的证。她可一点都不乖 你只要到网站主页填张表 交60美元,证书就寄到你家去 这不是我们认为她是个蠢货的唯一原因 她还说 你应该吃大量的暗绿色叶子 因为它们含有大量叶绿素,能给你的血液提供氧气 只要学过生物学的人都知道 叶绿素和叶绿体 只通过光合作用产生氧气 如果你把菠菜吃下去,胃里肯定一片漆黑
Next, we need proper science, proper evidence. So: "Red wine can help prevent breast cancer." This is a headline from The Daily Telegraph in the UK. "A glass of red wine a day could help prevent breast cancer." So you find this paper, and find that it is a real piece of science. It's a description of the changes in the behavior of one enzyme when you drip a chemical extracted from some red grape skin onto some cancer cells in a dish on a bench in a laboratory somewhere. And that's a really useful thing to describe in a scientific paper. But on the question of your own personal risk of getting breast cancer if you drink red wine, it tells you absolutely bugger all. Actually, it turns out that your risk of breast cancer increases slightly with every amount of alcohol you drink. So what we want are studies in real human people.
接下来,我们需要正确的科学,正当的证据 “红酒能防止乳腺癌” 这是英国每日电讯报的头条 “每天一杯红酒能防止乳腺癌” 你读了报纸 会觉得真是科学的 其解释说,在一个什么实验室里 一个凳子上有个装着癌细胞的碟子 你把红葡萄皮的提取物滴在细胞上 就有个酶发生变化 在一个有科学性的报纸上 如此描述是很有用 但是至于你喝红酒患乳腺癌风险的事 它只字没提 它什么都没说 事实上,如果你每喝一次酒 患乳腺癌的机率 都会相应轻微地上升 我们需要的是针对人进行的研究
And here's another example. This is from Britain's "leading" diet nutritionist in the Daily Mirror, our second-biggest selling newspaper. "An Australian study in 2001 found that olive oil, in combination with fruits, vegetables and pulses, offers measurable protection against skin wrinklings," and give the advice: "If you eat olive oil and vegetables, you'll have fewer wrinkles." They helpfully tell you how to find the paper, and what you find is an observational study. Obviously, nobody has been able to go back to 1930, get all the people born in one maternity unit, and half of them eat lots of fruit and veg and olive oil, half of them eat McDonald's, and then we see how many wrinkles you've got later.
这是另一个例子 来自英国每日镜报的人气营养师 镜报是我们全国销售量第二的报纸 “2001年澳大利亚一项研究 表明橄榄油与水果,蔬菜和豆子一起食用 对皮肤防皱有可观的效果” 然后他们开出建议: “如果你使用橄榄油和蔬菜,你的皱纹就会减少” 他们还给出文献出处 如果你去找该论文,会发现它是个观察性研究 显然没有人 能回到1930年 找到在同一个产科出生的所有人群样本 让一半人大量食用水果蔬菜和橄榄油 另一半吃麦当劳 然后看看他们长了多少皱纹
You have to take a snapshot of how people are now. And what you find is, of course: people who eat veg and olive oil have fewer wrinkles. But that's because people who eat fruit and veg and olive oil are freaks -- they're not normal, they're like you; they come to events like this.
你得存照纪录人们的样子 当然你发现 吃水果蔬菜和橄榄油的人皱纹少 但那是因为吃水果蔬菜和橄榄油的人 他们是怪胎,不正常,和你一样; 他们来参加这样的活动
(Laughter)
他们优雅,富有,不大可能从事户外工作
They're posh, they're wealthy, less likely to have outdoor jobs, less likely to do manual labor, they have better social support, are less likely to smoke; for a host of fascinating, interlocking social, political and cultural reasons, they're less likely to have wrinkles. That doesn't mean it's the vegetables or olive oil.
很少从事体力劳动 他们有更好的社会基础,不大抽烟- 所以是因为整体关联的 社会政治文化的缘故 他们较不易产生皱纹 这不意味着是蔬菜或橄榄油的功劳 (笑声)
(Laughter)
做试验往往是最好的选择
So ideally, what you want to do is a trial. People think they're familiar with the idea of a trial. Trials are old; the first one was in the Bible, Daniel 1:12. It's straightforward: take a bunch of people, split them in half, treat one group one way, the other group, the other way. A while later, you see what happened to each of them. I'm going to tell you about one trial, which is probably the most well-reported trial in the UK news media over the past decade. This is the trial of fish oil pills. The claim: fish oil pills improve school performance and behavior in mainstream children. They said, "We did a trial. All the previous ones were positive, this one will be too." That should ring alarm bells: if you know the answer to your trial, you shouldn't be doing one. Either you've rigged it by design, or you've got enough data so there's no need to randomize people anymore.
每个人都觉得这是他们熟悉的话题 试验是老话题。第一个试验是圣经里-《但以理书》第一章第十二节 非常简单-找一群人,分两组 用不同的方式分别对待两组人 之后你跟着他们 看他们都怎么样了 我要给你讲的试验 也许是过去十年间英国媒体上 曝光率最高的试验 这就是关于鱼肝油胶囊的试验 这个说法是鱼肝油胶囊能提高大部分学生的在校表现 和行为习惯 他们说“我们做过试验 之前都显示正面结果,我们可以肯定这次也是” 这是个警示 如果你已经知道一个试验的结果,那还进行干什么 或者说如果实验设计就存在人为操纵性 或者你已经有足够的数据那就没有必要再随机挑选更多的人了 试验是这样进行的:
So this is what they were going to do in their trial: They were taking 3,000 children, they were going to give them these huge fish oil pills, six of them a day, and then, a year later, measure their school exam performance and compare their performance against what they predicted their exam performance would have been if they hadn't had the pills. Now, can anybody spot a flaw in this design?
他们找了三千名儿童 给他们大个儿的鱼肝油药片 每天6个 一年以后,他们去测量他们的在校测试表现 并把在校测试表现和 在没有摄入鱼肝油的情况下他们预期的测试表现 进行对比 你看出了设计缺陷吗?
(Laughter)
临床医学试验方法论的教授
And no professors of clinical trial methodology are allowed to answer this question. So there's no control group. But that sounds really techie, right? That's a technical term. The kids got the pills, and their performance improved.
不允许回答这个问题 是的,没有对照组! 这听上去挺技术范儿 这是个术语 食用了药片的孩子表现提高了
What else could it possibly be if it wasn't the pills? They got older; we all develop over time. And of course, there's the placebo effect, one of the most fascinating things in the whole of medicine. It's not just taking a pill and performance or pain improving; it's about our beliefs and expectations, the cultural meaning of a treatment. And this has been demonstrated in a whole raft of fascinating studies comparing one kind of placebo against another. So we know, for example, that two sugar pills a day are a more effective treatment for gastric ulcers than one sugar pill. Two sugar pills a day beats one a day. That's an outrageous and ridiculous finding, but it's true. We know from three different studies on three different types of pain that a saltwater injection is a more effective treatment than a sugar pill, a dummy pill with no medicine in it, not because the injection or pills do anything physically to the body, but because an injection feels like a much more dramatic intervention. So we know that our beliefs and expectations can be manipulated, which is why we do trials where we control against a placebo, where one half of the people get the real treatment, and the other half get placebo.
不然还能怎样呢? 他们长大了,我们都会随着时间不断发展 当然,这里还有安慰效应在起作用 安慰效应是医学上最不可思议的玩意之一 不仅仅是吃一个药片,你的表现提升,痛苦缓解这么简单 而是关乎我们的信念和期待 这就是治疗的文化意义 大量研究已经通过不同的安慰剂对照试验 展示了这种效应 我们知道,比如说,每天2个糖丸 比一个糖丸在治疗胃溃疡上 更有效 每天2个糖丸胜过每天1个糖丸 这是个令人吃惊的荒唐发现,但这是真的 针对3种不同的痛症的3个研究显示 盐水注射比食用糖丸对痛症更有效 糖丸里头根本没有药- 并不是说注射或者药丸对身体有任何物理影响 而是因为感觉上注射是一种更强力的手段 我们知道我们的信念和期待 是可被操纵的 这就是为什么试验上 需要安慰剂对照组- 这样一半人接受真正的治疗 一半人得到安慰剂
But that's not enough. What I've just shown you are examples of the very simple and straightforward ways that journalists and food supplement pill peddlers and naturopaths can distort evidence for their own purposes. What I find really fascinating is that the pharmaceutical industry uses exactly the same kinds of tricks and devices, but slightly more sophisticated versions of them, in order to distort the evidence they give to doctors and patients, and which we use to make vitally important decisions.
但这并不够 我刚刚展示的是非常简单直观的例子 记者、保健食品商贩 和理疗家 都能为各自的目的歪曲证据 真正令人惊讶的是 制药产业 用一样的手段和方式 只不过更加隐秘精巧 来歪曲他们给医生和患者的证据 而那些是我们用来做重要决定的证据
So firstly, trials against placebo: everybody thinks a trial should be a comparison of your new drug against placebo. But in a lot of situations that's wrong; often, we already have a good treatment currently available. So we don't want to know that your alternative new treatment is better than nothing, but that it's better than the best available treatment we have. And yet, repeatedly, you consistently see people doing trials still against placebo. And you can get licensed to bring your drug to market with only data showing that it's better than nothing, which is useless for a doctor like me trying to make a decision.
首先,安慰剂对照组: 谁都知道要用新药 和安慰剂对照组做试验 但是很多情况下这是错的 因为通常我们目前已经有一个有效的治疗方法 所以我们想要知道的不是你的新疗法 比坐以待毙强 我们想知道的是它是不是比目前的疗法更有效 但是你总是看到他们做 安慰剂对照试验 这样你就能拿到许可证进入市场了 而试验数据只显示此药只不过比什么都没有好点 这对像我一样的医生要做决定一点帮助都没有
But that's not the only way you can rig your data. You can also rig your data by making the thing you compare your new drug against really rubbish. You can give the competing drug in too low a dose, so people aren't properly treated. You can give the competing drug in too high a dose, so people get side effects. And this is exactly what happened with antipsychotic medication for schizophrenia. Twenty years ago, a new generation of antipsychotic drugs were brought in; the promise was they would have fewer side effects. So people set about doing trials of the new drugs against the old drugs. But they gave the old drugs in ridiculously high doses: 20 milligrams a day of haloperidol. And it's a foregone conclusion if you give a drug at that high a dose, it will have more side effects, and your new drug will look better.
这还不是操纵数据的唯一手段 你还可以通过 将你的新药和真的废物做对照试验 来操纵数据 你可以将对照药物剂量控制在非常低的水平 这样人们没有得到适当的治疗 也可以将对照药物剂量控制在非常高的水平 这样就产生副作用 治疗精神分裂症的安定药 就是这么干的 20年前,一批新的安定药面世 有承诺说它们的副作用更低 人们就对这些新药做了试验 跟旧的药对比 但他们使用的旧药剂量无比之高- 每天20毫克的氟哌丁苯 毫无疑问 如果这么大的剂量 肯定会导致更多的副作用从而让新药看上去更好
Ten years ago, history repeated itself, when risperidone, the first of the new-generation antipsychotic drugs, came off copyright, so anybody could make copies. Everybody wanted to show their drug was better than risperidone, so you see trials comparing new antipsychotic drugs against risperidone at eight milligrams a day. Again, not an insane dose, not an illegal dose, but very much at the high end of normal. So you're bound to make your new drug look better. And so it's no surprise that overall, industry-funded trials are four times more likely to give a positive result than independently sponsored trials.
10年前,历史重演,有趣的是 当利培酮,这一第二代抗精神病药的先锋 产权到期的时候,谁都可以进行生产 每个人都想展示他们的药比利培酮好 接着你就看到一堆新的抗精神病药的对照试验 和每天8毫克的利培酮对照 这个剂量不算疯狂,不是违法 但绝对超出正常 所以你肯定能让新药表现更好 果不其然 制药业赞助的试验 比私人赞助试验得到正面结果(阳性结果)的机率 要高出4倍
But -- and it's a big but --
但是-这是一个很大的但是-
(Laughter)
(笑声)
it turns out, when you look at the methods used by industry-funded trials, that they're actually better than independently sponsored trials. And yet, they always manage to get the result that they want. So how does this work?
结果是 如果你查看制药业赞助的试验使用的方法 反而比私人赞助试验的方法 更好 不过他们总能得到他们想要的结果 那这是怎么回事?
(Laughter)
怎么解释这一奇怪现象?
How can we explain this strange phenomenon? Well, it turns out that what happens is the negative data goes missing in action; it's withheld from doctors and patients. And this is the most important aspect of the whole story. It's at the top of the pyramid of evidence. We need to have all of the data on a particular treatment to know whether or not it really is effective. There are two different ways you can spot whether some data has gone missing. You can use statistics or you can use stories. I prefer statistics, so that's what I'll do first.
实际情况是 负面结果的数据完全丢失; 医生和患者扣留着这些信息 这是整个过程里最重要的一个方面 这是证据金字塔的塔尖 我们需要一个疗法的所有数据 才能知道它是否有效 有两种方法你可以发现 是否有数据丢失 可以用统计学,或者事例 我个人倾向统计学,所以我首先做的就是
This is a funnel plot. A funnel plot is a very clever way of spotting if small negative trials have disappeared, have gone missing in action. This is a graph of all of the trials done on a particular treatment. As you go up towards the top of the graph, what you see is each dot is a trial. As you go up, those are bigger trials, so they've got less error; they're less likely to be randomly false positives or negatives. So they all cluster together. The big trials are closer to the true answer. Then as you go further down at the bottom, what you can see is, on this side, spurious false negatives, and over on this side, spurious false positives. If there is publication bias, if small negative trials have gone missing in action, you can see it on one of these graphs. So you see here that the small negative trials that should be on the bottom left have disappeared. This is a graph demonstrating the presence of publication bias in studies of publication bias. And I think that's the funniest epidemiology joke you will ever hear.
漏斗图分析 漏斗图是个非常好的方法 来查看是否有少量负面结果丢失 这是针对某项疗法的 所有试验图表 图片上部 每一个点是一个试验 越往上,试验规模越大,误差也就越小 也就是越少随机的假阳性和假阴性结果 (阳性即表示试验结果是肯定治疗药物的疗效的,译者注) 它们会聚集在一起 越大的试验越接近事实 越往下 可以发现,这一边是伪造的假阴性结果 那边是伪造的假阳性结果 如果有发表偏倚(有统计学意义的结果更易被发表) 如果得出负面结果的小规模试验数据丢失 你可以在这些图表中找到 这里可以看见,应该在图表左下的 得出负面结果的小规模试验不见了 这个图表展示的是关于发表偏倚的研究里 出现的发表偏倚 我觉得这是你听过的最有意思的 关于“流行病”的笑话
(Laughter)
这就是统计证明方法
That's how you can prove it statistically. But what about stories? Well, they're heinous, they really are. This is a drug called reboxetine. This is a drug which I, myself, have prescribed to patients. And I'm a very nerdy doctor. I hope I go out of my way to try and read and understand all the literature. I read the trials on this. They were all positive, all well-conducted. I found no flaw. Unfortunately, it turned out, that many of these trials were withheld. In fact, 76 percent of all of the trials that were done on this drug were withheld from doctors and patients. Now if you think about it, if I tossed a coin a hundred times, and I'm allowed to withhold from you the answers half the times, then I can convince you that I have a coin with two heads. If we remove half of the data, we can never know what the true effect size of these medicines is.
那事例法呢? 那个就比较可恶了 有种药叫瑞波西汀(抗抑郁药) 我曾给一位病人开过这个药 而我是个超级书呆子的医生 我寄希望于阅读和理解所有文献 我读了试验资料,都是正面结果,都是正规操作 没发现漏洞 但不幸的是 很多试验结果被扣留 此药有76%的 试验结果都 被医生和病人保留 你想想 如果我把硬币扔一百次 我可以保留一半结果 不告诉你 然后我就能说服你 我的硬币两面都是人头像 如果去掉一半数据 我们绝不可能知道这些药的真正的效果
And this is not an isolated story. Around half of all of the trial data on antidepressants has been withheld, but it goes way beyond that. The Nordic Cochrane Group were trying to get ahold of the data on that to bring it all together. The Cochrane Groups are an international nonprofit collaboration that produce systematic reviews of all of the data that has ever been shown. And they need to have access to all of the trial data. But the companies withheld that data from them. So did the European Medicines Agency -- for three years.
这不是个偶发事件 针对抗抑郁症药的试验数据有一半左右都被保留 事实比着更糟 Nordic Cochrane集团曾尝试 收集那些被保留的数据 Nordic Cochrane是个国际性非盈利团体机构 提供对所有公开数据的系统性的评论 他们需要所有试验数据的查看权限 但是制药商保留了数据结果 欧洲药物管理局也这样 做了3年 这个问题目前没有解决方案
This is a problem that is currently lacking a solution. And to show how big it goes, this is a drug called Tamiflu, which governments around the world have spent billions and billions of dollars on. And they spend that money on the promise that this is a drug which will reduce the rate of complications with flu. We already have the data showing it reduces the duration of your flu by a few hours. But I don't care about that, governments don't care. I'm sorry if you have the flu, I know it's horrible, but we're not going to spend billions of dollars trying to reduce the duration of your flu symptoms by half a day. We prescribe these drugs. We stockpile them for emergencies on the understanding they'll reduce the number of complications, which means pneumonia and death. The infectious diseases Cochrane Group, which are based in Italy, has been trying to get the full data in a usable form out of the drug companies, so they can make a full decision about whether this drug is effective or not, and they've not been able to get that information. This is undoubtedly the single biggest ethical problem facing medicine today. We cannot make decisions in the absence of all of the information.
为了告诉你们这个问题的严重性,给你们举一个叫达菲的药的例子 各国政府 花了巨资在此药上 他们承诺 这个药能降低 流感的并发症几率 我们已有数据显示 它能减少几小时流感症状的持续时间 我不关心这个,政府也不关心 很抱歉你得流感了,我知道那很糟糕 但我们不可能花上百万美元 只为了减少半天你的 流感症状 我们开药,在急诊室有大量存货 觉得这能降低并发症数 也就是说肺炎或者死亡 位于意大利的Cochrane尝试着 从制药公司获取 关于该药的所有有用数据 以便他们判断 此药是否有效 他们没能拿到信息 毫无疑问 这是如今医学界面临的 一个重大道德问题 没有信息 我们无法做决定
So it's a little bit difficult from there to spin in some kind of positive conclusion. But I would say this: I think that sunlight is the best disinfectant. All of these things are happening in plain sight, and they're all protected by a force field of tediousness. And I think, with all of the problems in science, one of the best things that we can do is to lift up the lid, finger around at the mechanics and peer in.
据此想得出些正面结论 是有些困难 但是我想说: 阳光是 最好的杀菌剂 日光之下无新事 这些事物都受 一种单调的力场所保护 我认为,对于所有科学问题 我们能做的最好的就是 掀开事物的表层 摸清来去一窥究竟
Thank you very much.
非常感谢
(Applause)
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