What doctors don't know about the drugs they prescribe | Ben Goldacre

Translator: Joseph Geni Reviewer: Morton Bast

翻译人员: Bear Jin 校对人员: dahong zhang

Hi. So, this chap here,

嗨！报纸上的这个家伙

he thinks he can tell you the future.

认为他能预知未来。

His name is Nostradamus, although here the Sun have

他叫诺查丹玛斯，尽管太阳报

made him look a little bit like Sean Connery. (Laughter)

把他画得有点像肖恩·康纳利。（笑声）

And like most of you, I suspect, I don't really believe

像你们一样，我很怀疑，我不太相信

that people can see into the future.

人真能预知未来。

I don't believe in precognition, and every now and then,

我不相信先知，你常常会

you hear that somebody has been able to predict something that happened in the future,

听说有人能够预知某事的发生，

and that's probably because it was a fluke, and we only

但这可能仅仅是因为瞎猫撞着死耗子，而且我们也仅仅

hear about the flukes and about the freaks.

听说了那些侥幸和怪异之事。

We don't hear about all the times that people got stuff wrong.

我们可不会听说那些被预测搞砸的事情。

Now we expect that to happen with silly stories

我们认为这就是关于预知的

about precognition, but the problem is,

荒诞故事的原因，但问题在于，

we have exactly the same problem in academia

同样问题也存在于学术领域，

and in medicine, and in this environment, it costs lives.

和医学方面，这关乎人命。

So firstly, thinking just about precognition, as it turns out,

所以，首先想想“预知”这个问题，因为去年

just last year a researcher called Daryl Bem conducted

有一个叫达里尔·贝姆的研究者进行了

a piece of research where he found evidence

一个研究，他发现了关于大学生的

of precognitive powers in undergraduate students,

预知能力的证据，

and this was published in a peer-reviewed academic journal

并且这篇论文被发表在了一本同行评议的学术期刊中。

and most of the people who read this just said, "Okay, well,

很多读过这篇论文的人都说：“好吧，嗯，

fair enough, but I think that's a fluke, that's a freak, because I know

有道理，但我认为这是巧合，因为我知道

that if I did a study where I found no evidence

如果我进行研究，并得出没有任何证据

that undergraduate students had precognitive powers,

表明大学生有预知能力，

it probably wouldn't get published in a journal.

这篇论文很可能不会被在期刊中发表。

And in fact, we know that that's true, because

其实，我们知道这个问题是存在的，

several different groups of research scientists tried

因为几组科学家尝试

to replicate the findings of this precognition study,

重复关于预知能力的研究，

and when they submitted it to the exact same journal,

但当他们试图发表在这同一本期刊上时，

the journal said, "No, we're not interested in publishing

期刊编辑说：“不，我们对重复实验不感兴趣。

replication. We're not interested in your negative data."

我们对你的负面数据不感兴趣。”

So this is already evidence of how, in the academic

所以这就是证据，在学术文献中，

literature, we will see a biased sample of the true picture

我们会看到真实情况的例证，

of all of the scientific studies that have been conducted.

几乎所有科学研究都是存在偏见。

But it doesn't just happen in the dry academic field of psychology.

但这并不只发生在枯燥的心理学领域。

It also happens in, for example, cancer research.

在癌症研究方面这个问题也存在。

So in March, 2012, just one month ago, some researchers

所以，在2012年3月，也就是一个月前，一些研究人员

reported in the journal Nature how they had tried

在自然杂志上发表文章，表示他们如何尝试

to replicate 53 different basic science studies looking at

重复53个关于癌症潜在疗法的

potential treatment targets in cancer,

基本科学研究，

and out of those 53 studies, they were only able

结果在这53个研究中，他们只能成功

to successfully replicate six.

重复其中六个。

Forty-seven out of those 53 were unreplicable.

剩余47个实验则无法成功重复。

And they say in their discussion that this is very likely

他们在分析中指出这很有可能是

because freaks get published.

因为怪异的结果容易被发表。

People will do lots and lots and lots of different studies,

人们会做许多许多不同的实验，

and the occasions when it works they will publish,

实验成功就会被发表，

and the ones where it doesn't work they won't.

不成功则难见天日。

And their first recommendation of how to fix this problem,

他们对解决这个问题的第一个建议，

because it is a problem, because it sends us all down blind alleys,

因为这确实是个问题，它把我们都送进死胡同，

their first recommendation of how to fix this problem

他们纠正这个问题的第一个建议就是

is to make it easier to publish negative results in science,

让在科学界发表负面结果变得更加容易，

and to change the incentives so that scientists are

并改变科学家们的奖励机制，鼓励他们

encouraged to post more of their negative results in public.

更多地公开发表负面的结果。

But it doesn't just happen in the very dry world

这不仅仅发生在枯燥的

of preclinical basic science cancer research.

临床基础癌症研究。

It also happens in the very real, flesh and blood

它还发生在活生生的

of academic medicine. So in 1980,

学术医学领域。在1980年，

some researchers did a study on a drug called lorcainide,

一些研究人员研究了一种叫劳卡胺的药物，

and this was an anti-arrhythmic drug,

这是一种抗心律失常药，

a drug that suppresses abnormal heart rhythms,

可以抑制不正常的心率。

and the idea was, after people have had a heart attack,

研究者想法是，当病人心脏病发作，

they're quite likely to have abnormal heart rhythms,

他们很可能心率失常，

so if we give them a drug that suppresses abnormal heart

所以如果我们给他们抑制心率失常的药，

rhythms, this will increase the chances of them surviving.

他们的存活率就会增加。

Early on its development, they did a very small trial,

在研究早期，他们进行了一个非常小规模的实验，

just under a hundred patients.

只有100个病人参加。

Fifty patients got lorcainide, and of those patients, 10 died.

50人服用劳卡胺，他们中有10人死了。

Another 50 patients got a dummy placebo sugar pill

另外50人服用了假的（安慰剂糖片）药片，

with no active ingredient, and only one of them died.

没有摄入任何有效成分，他们中只有1人死了。

So they rightly regarded this drug as a failure,

所以研究人员很诚实地将这种药列为失败产品，

and its commercial development was stopped, and because

有关的商业开发马上停止，而导致了

its commercial development was stopped, this trial was never published.

这次研究的结果一直没有发表。

Unfortunately, over the course of the next five, 10 years,

不幸的是，在接下来的五到十年里，

other companies had the same idea about drugs that would

其它公司也有制造同样药物的想法——

prevent arrhythmias in people who have had heart attacks.

对心脏病人使用抗心律不齐药物。

These drugs were brought to market. They were prescribed

这些药物被投入市场，并被

very widely because heart attacks are a very common thing,

广为使用，因为心脏病是种很常见的病。

and it took so long for us to find out that these drugs

我们花了很长时间才意识到这些药物

also caused an increased rate of death

致使患者死亡率上升。

that before we detected that safety signal,

在我们发现到这一点之前，

over 100,000 people died unnecessarily in America

美国十万多条本可挽留的生命就因

from the prescription of anti-arrhythmic drugs.

使用这种抗心律不齐药物而失去。

Now actually, in 1993,

实际上，在1993年，

the researchers who did that 1980 study, that early study,

那些在1980年进行早期实验的研究人员

published a mea culpa, an apology to the scientific community,

发表了公开道歉，以对科学界表达歉意。

in which they said, "When we carried out our study in 1980,

他们写道：“当我们在1980年进行研究时，

we thought that the increased death rate that occurred

我们以为劳卡胺实验组的

in the lorcainide group was an effect of chance."

死亡率上升只是巧合罢了。”

The development of lorcainide was abandoned for commercial reasons,

劳卡胺的研发因商业原因被停止，

and this study was never published;

而这项研究也从未被发表。

it's now a good example of publication bias.

这就是‘发表偏倚’(Publication bias)的极佳例子。

That's the technical term for the phenomenon where

‘发表偏倚’(Publication bias)是一个用来形容负面数据被忽视，

unflattering data gets lost, gets unpublished, is left

不被发表，的特有名词

missing in action, and they say the results described here

之后，他们得出的结论是

"might have provided an early warning of trouble ahead."

“本可以在灾难之前提前敲响警钟。”

Now these are stories from basic science.

这是些基础科学界的故事。

These are stories from 20, 30 years ago.

这些都是20，30年前的老故事了。

The academic publishing environment is very different now.

如今，学术出版业大环境已经今非昔比。

There are academic journals like "Trials," the open access journal,

现在有类似《试验》的开源期刊(the open access journal)，

which will publish any trial conducted in humans

这些期刊是不论结果好坏，只要关于人体试验的

regardless of whether it has a positive or a negative result.

悉数发表的学术期刊。

But this problem of negative results that go missing in action

但负面结果被忽视的问题

is still very prevalent. In fact it's so prevalent

还是很严重。实际上，这严重到了

that it cuts to the core of evidence-based medicine.

威胁“循证医药学”的根本。

So this is a drug called reboxetine, and this is a drug

这是一种叫做瑞波西汀的药物，之前

that I myself have prescribed. It's an antidepressant.

我也开过这药的处方。这是一种抗抑郁的药物。

And I'm a very nerdy doctor, so I read all of the studies

而我又比较死板书呆子，所以我浏览了

that I could on this drug. I read the one study that was published

所有我能找到关于此药的文章。我读到的其中一篇声称

that showed that reboxetine was better than placebo,

瑞波西汀比安慰剂要有效果，

and I read the other three studies that were published

我又读到另外三篇声称

that showed that reboxetine was just as good as any other antidepressant,

瑞波西汀和其他抗抑药物的效果没什么差别，

and because this patient hadn't done well on those other antidepressants,

就因为那个病人对其他抗抑郁的药物没什么反应，

I thought, well, reboxetine is just as good. It's one to try.

所以我觉得，瑞波西汀效果也不错。试试也没什么坏处。

But it turned out that I was misled. In fact,

但最终证明我是被误导了。实际上，

seven trials were conducted comparing reboxetine

有七项关于瑞波西汀和

against a dummy placebo sugar pill. One of them

安慰糖片的比较试验。其中一项

was positive and that was published, but six of them

效果出众也得以发表，其他六项

were negative and they were left unpublished.

无效果，导致无法发表结论。

Three trials were published comparing reboxetine

三项发表的试验记载

against other antidepressants in which reboxetine

在瑞波西汀和其他抗抑郁药物的对比中，瑞波西汀

was just as good, and they were published,

效果同样显著，并得以发表，

but three times as many patients' worth of data was collected

而另外收集的多达三倍的病例数据

which showed that reboxetine was worse than

显示瑞波西汀的表现

those other treatments, and those trials were not published.

远不如其它药物的疗效，而这些试验结果没有被发表。

I felt misled.

我感觉被误导了。

Now you might say, well, that's an extremely unusual example,

也许你会说，那可能是个案中的个案吧，

and I wouldn't want to be guilty of the same kind of

我也不必自己和自己较真，

cherry-picking and selective referencing

不必为其他人这种只挑有利的选择性

that I'm accusing other people of.

发表而指责别人。

But it turns out that this phenomenon of publication bias

但结果证实这种“发表偏倚”

has actually been very, very well studied.

已经被很深入的研究过了。

So here is one example of how you approach it.

举个例子，你如何看待它。

The classic model is, you get a bunch of studies where

经典的例子就是，你有了一堆

you know that they've been conducted and completed,

已经临床使用过并有结论的试验

and then you go and see if they've been published anywhere

而你要找学术文献机构

in the academic literature. So this took all of the trials

询问是否曾经有发表。他们寻找了所有抗抑郁药物有关的

that had ever been conducted on antidepressants

被食品药物管理局15年前审批的

that were approved over a 15-year period by the FDA.

相关临床案例。

They took all of the trials which were submitted to the FDA as part of the approval package.

他们根据所有曾经上交给食品医药管理局的试验案例作为基础。

So that's not all of the trials that were ever conducted on these drugs,

所以那并不是所有此类药物的所有临床试验结果，

because we can never know if we have those,

因为我们不知道那些没有被公布的，

but it is the ones that were conducted in order to get the marketing authorization.

只知道那些为了获得上市批准而进行试验研究的结果。

And then they went to see if these trials had been published

之后，他们去了解那些试验有没有被发表

in the peer-reviewed academic literature. And this is what they found.

在那些需同行审核的学术期刊中。这是他们的发现结果。

It was pretty much a 50-50 split. Half of these trials

是大致上平分秋色。现实情况，一半试验显示

were positive, half of them were negative, in reality.

效果显著，另外一半显示效果不显著。

But when they went to look for these trials in the peer-reviewed academic literature,

但他们从那些需审核的学术机构里搜索那些试验的时候，

what they found was a very different picture.

他们发现结果是截然不同的。

Only three of the negative trials were published,

只有三项效果负面的试验被发表了出来，

but all but one of the positive trials were published.

而除了一例几乎所有效果显著的试验案例都被发表了出去。

Now if we just flick back and forth between those two,

当我们前后跳转进行两者对比的话，

you can see what a staggering difference there was

你能发现横在现实和

between reality and what doctors, patients,

医生、病人、卫生服务专员、专业学者

commissioners of health services, and academics

所能读到的审核的学术期刊文献，之间消息的鸿沟了。

were able to see in the peer-reviewed academic literature.

所能读到的审核的学术期刊文献，之间消息的鸿沟了。

We were misled, and this is a systematic flaw

我们被误导了，这是医药学核心中的体制漏洞。

in the core of medicine.

我们被误导了，这是医药学核心中的体制漏洞。

In fact, there have been so many studies conducted on

实际上，如今已经有很多关于

publication bias now, over a hundred, that they've been

“发表偏倚”的研究了，

collected in a systematic review, published in 2010,

在2010年发表的被收集并系统性的调查中，

that took every single study on publication bias

他们能找到的所有的“发表偏倚”的研究

that they could find.

“发表偏倚”的试验案例有一百多项。

Publication bias affects every field of medicine.

“发表偏倚”影响了医学的所有领域。

About half of all trials, on average, go missing in action,

大约一半的试验，被遗忘忽视，

and we know that positive findings are around twice as likely

我们还发现，有效果的结果发表的几率

to be published as negative findings.

几乎是没效果发表几率的两倍。

This is a cancer at the core of evidence-based medicine.

这是循证医药学中的毒瘤。

If I flipped a coin 100 times but then

如果我抛100次硬币，但是

withheld the results from you from half of those tosses,

隐瞒一半的投掷结果，

I could make it look as if I had a coin that always came up heads.

我就能让它看以来是一个永远头像朝上的硬币。

But that wouldn't mean that I had a two-headed coin.

但这不代表我这硬币有两面都是头像。

That would mean that I was a chancer

这只能说我是个投机者

and you were an idiot for letting me get away with it. (Laughter)

而你是相信我说法的白痴。（笑声）

But this is exactly what we blindly tolerate

但这就是我们在循证医药学中盲目纵容的现状。

in the whole of evidence-based medicine.

但这就是我们在循证医药学中盲目纵容的现状。

And to me, this is research misconduct.

对我来说，这是学术不端行为。

If I conducted one study and I withheld

如果我做某项研究，而我隐瞒了

half of the data points from that one study,

此研究中一半的数据，

you would rightly accuse me, essentially, of research fraud.

你就有权利指控我，学术诈骗。

And yet, for some reason, if somebody conducts

但出于某种原因，如果某人做了

10 studies but only publishes the five that give the result that they want,

10项研究但只发表其中他希望的5项的话，

we don't consider that to be research misconduct.

我们却不会考虑这是学术不端。

And when that responsibility is diffused between

但当学术不端的责任分散于学术网络，学术期刊，商业赞助商，期刊编辑的时候，

a whole network of researchers, academics,

但当学术不端的责任分散于学术网络，学术期刊，商业赞助商，期刊编辑的时候，

industry sponsors, journal editors, for some reason

但当学术不端的责任分散于学术网络，学术期刊，商业赞助商，期刊编辑的时候，

we find it more acceptable,

不知怎么的，我们觉得这样是可以接受的，

but the effect on patients is damning.

但这对病人的后果是惨痛的。

And this is happening right now, today.

如今这样的情况还在发生。

This is a drug called Tamiflu. Tamiflu is a drug

这是种叫达菲的药物。达菲是

which governments around the world have spent billions

全球政府花费了数十亿美元的

and billions of dollars on stockpiling,

资金作为应急储备的，

and we've stockpiled Tamiflu in panic,

我们储备达菲，以备不时之需，

in the belief that it will reduce the rate of complications of influenza.

因为我们相信，它能减少流感所带来的并发症。

Complications is a medical euphemism for pneumonia

并发症则是医学上对肺炎和死亡的

and death. (Laughter)

婉转说法。（笑声）

Now when the Cochrane systematic reviewers

如今，当科克伦(Cochrane临床对照试验资料库)系统审核员

were trying to collect together all of the data from all

想收集所有关于达菲临床应用的，

of the trials that had ever been conducted on whether Tamiflu actually did this or not,

是否有效的试验案例时，

they found that several of those trials were unpublished.

他们发现很多试验是未被发表的。

The results were unavailable to them.

他们无法找到那些实验的结果。

And when they started obtaining the writeups of those trials through various different means,

当他们通过不同渠道，通过《信息自由法案》，

through Freedom of Information Act requests, through

当他们通过不同渠道，通过《信息自由法案》，

harassing various different organizations, what they found was inconsistent.

向各种不同组织打探消息后，他们发现里面有很多矛盾的地方。

And when they tried to get a hold of the clinical study reports,

当他们想查看那一万多页

the 10,000-page long documents that have

包括了所有试验结果信息的

the best possible rendition of the information,

临床学术报告的时候，

they were told they weren't allowed to have them.

他们被告知，他们无权使用。

And if you want to read the full correspondence

如果你想知道那些制药公司

and the excuses and the explanations given by the drug company,

对此给出的解释和借口全文的话，

you can see that written up in this week's edition

你可以关注一下这周出版的

of PLOS Medicine.

《公共科学图书馆•医学》的期刊。

And the most staggering thing of all of this, to me,

但对我来说，最惊人的事情是，

is that not only is this a problem, not only do we recognize

不仅之前讨论的这个问题，和我们是否意识到了

that this is a problem, but we've had to suffer fake fixes.

这个问题，还包括我们要忍受装作问题已被解决。

We've had people pretend that this is a problem that's been fixed.

我们让人们以为这个问题已经解决了。

First of all, we had trials registers, and everybody said,

首先，我们有试验注册，所有人都说，

oh, it's okay. We'll get everyone to register their trials, they'll post the protocol,

这样就行了。我们让所有人都注册他们的试验案例，他们会发布行业规则的，

they'll say what they're going to do before they do it,

事先宣布他们要做什么了，

and then afterwards we'll be able to check and see if all the trials which

之后，我们就能查出是否所有的进行过的试验案例都被发表了。

have been conducted and completed have been published.

之后，我们就能查出是否所有的进行过的试验案例都被发表了。

But people didn't bother to use those registers.

但人们并没有乖乖来注册。

And so then the International Committee of Medical Journal Editors came along,

之后国际医学杂志编辑委员会跳出来，

and they said, oh, well, we will hold the line.

他们说，那好吧，我们会坚守底线的。

We won't publish any journals, we won't publish any trials,

除非试验案例之前已经注册过了，

unless they've been registered before they began.

否则我们是不会让它发表在学术期刊上的。

But they didn't hold the line. In 2008, a study was conducted

但他们还是没守住底线。2008年，一篇对此的研究

which showed that half of all of trials published by journals

表明，被国际医学杂志编辑委员会成员

edited by members of the ICMJE

审核的上述期刊中半数的试验

weren't properly registered, and a quarter of them weren't registered at all.

没有被完整注册在案，四分一的案例甚至就根本没有注册。

And then finally, the FDA Amendment Act was passed

最后，食品药物修正法案在几年后通过施行

a couple of years ago saying that everybody who conducts

强调任何实施临床试验的人

a trial must post the results of that trial within one year.

都必须在之后一年内公布临床试验的结果。

And in the BMJ, in the first edition of January, 2012,

在英国医学杂志，2012年1月第一版，

you can see a study which looks to see if people kept

你能找到一项关于人们是否履行上述法案的研究

to that ruling, and it turns out that only one in five

结果表明只有五分一的人照此办理。

have done so.

结果表明只有五分一的人照此办理。

This is a disaster.

悲剧阿，悲剧。

We cannot know the true effects of the medicines

如果我们不能了解所有的相关信息，

that we prescribe if we do not have access

我们就无法了解我们所开的药物的

to all of the information.

真实疗效。

And this is not a difficult problem to fix.

但这问题不是那么难去克服的。

We need to force people to publish all trials

我们需要强制人们发表所有临床

conducted in humans, including the older trials,

试验的结果，包括较早以前的案例，

because the FDA Amendment Act only asks that you publish the trials conducted after 2008,

因为食品药物修正法只要求公开2008年之后的临床试验，

and I don't know what world it is in which we're only

我不知道循证医药学的世界会变成什么样，

practicing medicine on the basis of trials that completed in the past two years.

如果我们用药只依靠这两年里的实验数据。

We need to publish all trials in humans,

我们需要公布所有现用药物的所有临床试验的结果，包括较早以前的试验，

including the older trials, for all drugs in current use,

我们需要公布所有现用药物的所有临床试验的结果，包括较早以前的试验，

and you need to tell everyone you know

而且你们需要告诉你认识的所有人

that this is a problem and that it has not been fixed.

这是个问题，这个问题还有待解决。

Thank you very much. (Applause)

谢谢大家。（掌声）

(Applause)

（掌声）