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

Translator: Joseph Geni Reviewer: Morton Bast

譯者: Vivian Mig 審譯者: Geoff Chen

Hi. So, this chap here,

嗨各位! 這位仁兄呢

he thinks he can tell you the future.

自認可以預知未來

His name is Nostradamus, although here the Sun have

他的名字是諾斯特拉達姆士，但這張圖看起來

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

反倒有點像西恩康納瑞

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

我呢，跟大部分的人一樣

that people can see into the future.

不太相信人類能預見未來

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

我不信這套，但你時常會聽到

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

有些人能夠預測未來

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

大概都是僥倖猜中的吧

hear about the flukes and about the freaks.

我們也只能聽到這些不尋常的故事

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

看到人凸槌的機會卻很少

Now we expect that to happen with silly stories

我們以為只有預知未來這種事才會出錯

about precognition, but the problem is,

但實際上，

we have exactly the same problem in academia

學術界和醫藥界也有同樣的問題

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

出錯會賠上人命的

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

現在我們先把焦點放在預知未來上

just last year a researcher called Daryl Bem conducted

去年有位名叫Daryl Bem的研究員

a piece of research where he found evidence

做了一項研究，證明大學生

of precognitive powers in undergraduate students,

有預測未來的能力

and this was published in a peer-reviewed academic journal

研究結果收錄在一個同儕審查的學術期刊中

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

看過的人大部分表示

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

"好吧算他厲害，但這純粹是僥倖猜中，

that if I did a study where I found no evidence

因為我如果做了一個無法證明

that undergraduate students had precognitive powers,

大學生有預知能力的研究，

it probably wouldn't get published in a journal.

應該就沒有期刊會出版了"

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

事實也真的是如此

several different groups of research scientists tried

有數個研究團隊試圖

to replicate the findings of this precognition study,

重復這項研究的成果

and when they submitted it to the exact same journal,

當他們把結果呈給同樣的出版社時

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

出版社表示，"我們對同樣的研究沒興趣，

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

你們的結果與先前的相反，所以我們沒興趣"

So this is already evidence of how, in the academic

由此可見，在學術界裡

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

許多科學研究

of all of the scientific studies that have been conducted.

都存在一種特定偏見

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

這種導向不只出現在心理學研究

It also happens in, for example, cancer research.

在癌症的研究中也會出現

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

2012年三月，也就是一個月前

reported in the journal Nature how they had tried

幾位研究員在自然期刊中表示

to replicate 53 different basic science studies looking at

他們重新做了先前53種治療癌症的基本研究

potential treatment targets in cancer,

尋找治療癌症的可行方法

and out of those 53 studies, they were only able

53項研究中，

to successfully replicate six.

只有6項成功

Forty-seven out of those 53 were unreplicable.

有47項是失敗的

And they say in their discussion that this is very likely

討論過程中他們表示，這個結果很可能是因為

because freaks get published.

不尋常的事物容易備受矚目

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

人們做了一大堆研究

and the occasions when it works they will publish,

成功的實驗結果會被公諸於世

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

失敗的結果不會受到注意

And their first recommendation of how to fix this problem,

這些研究員對這個問題提出解決辦法

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

這個問題將大眾導入迷途

their first recommendation of how to fix this problem

他們認為處理這個問題的辦法

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

即是使失敗的研究結果受到更多重視

and to change the incentives so that scientists are

改變研究動機，鼓勵科學家勇於

encouraged to post more of their negative results in public.

公布失敗的結果

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

這不只發生在臨床基本癌症研究

of preclinical basic science cancer research.

這不只發生在臨床基本癌症研究

It also happens in the very real, flesh and blood

這也發生在活生生的學術醫藥中

of academic medicine. So in 1980,

1980年幾位研究員

some researchers did a study on a drug called lorcainide,

對一種叫lorcainide的藥物做研究

and this was an anti-arrhythmic drug,

這是一種抗心律失常藥

a drug that suppresses abnormal heart rhythms,

用來抑制異常的心搏

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

病人心臟病發後

they're quite likely to have abnormal heart rhythms,

很有可能心律不整

so if we give them a drug that suppresses abnormal heart

若給病人能夠抑制異常心搏的藥

rhythms, this will increase the chances of them surviving.

便能提高存活率

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

初期試用階段，他們對一百多名病患

just under a hundred patients.

做了一個試驗

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

五十名服用lorcainide的患者中，有十人死亡

Another 50 patients got a dummy placebo sugar pill

另外五十名服用單純糖做的藥丸

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

只有一個人死亡

So they rightly regarded this drug as a failure,

他們馬上認定這是個失敗的藥物

and its commercial development was stopped, and because

廣告活動也停止宣傳

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

因為如此，試驗結果也從未公布

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

不幸的是，五年、十年過後

other companies had the same idea about drugs that would

其他藥廠開發了同樣能

prevent arrhythmias in people who have had heart attacks.

抑制心臟病患異常心搏的藥

These drugs were brought to market. They were prescribed

這些藥在市面販售，又因為心臟疾病普遍

very widely because heart attacks are a very common thing,

這些藥經常變成處方藥物

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

我們花了很久的時間才發現

also caused an increased rate of death

這些藥物會提高死亡率

that before we detected that safety signal,

在我們發覺這些危險前

over 100,000 people died unnecessarily in America

美國有十萬人因服用抗心律失常藥而白白送命

from the prescription of anti-arrhythmic drugs.

美國有十萬人因服用抗心律失常藥而白白送命

Now actually, in 1993,

而在1993年

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

1980年做過早期試驗的那批研究員

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

發表了一篇悔過書，向科學界致歉

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

他們表示 "1980年進行lorcainide試驗時，

we thought that the increased death rate that occurred

我們以為死亡率的提升只是巧合"

in the lorcainide group was an effect of chance."

我們以為死亡率的提升只是機率問題"

The development of lorcainide was abandoned for commercial reasons,

基於商業因素，lorcainide停止研發

and this study was never published;

這項試驗結果也從未公布

it's now a good example of publication bias.

由此可見出版業的偏見

That's the technical term for the phenomenon where

也就是不起眼的資訊常遭到封殺

unflattering data gets lost, gets unpublished, is left

不是被埋沒就是沒下文

missing in action, and they say the results described here

他們表示，這個結果"原本有可能做為警惕"

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

他們表示，這個結果"原本有可能做為警惕"

Now these are stories from basic science.

以上只是基層科學方面的故事

These are stories from 20, 30 years ago.

而且距今也二、三十年了

The academic publishing environment is very different now.

現今的學術出版業已截然不同

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

有一個叫Trials(實驗)的公開期刊

which will publish any trial conducted in humans

收錄各種與人體有關的實驗結果

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

結果是好是壞都會被收錄

But this problem of negative results that go missing in action

但失敗的實驗結果仍普遍遭到隱埋

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

事實上這種情況甚至影響到

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

講究科學根據為重的藥物研發

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

這是一種叫rebozetine的藥

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

我曾把這種藥物開做處方，對抗憂鬱症

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

身為一個菜鳥醫生，我竭盡所能的查詢

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

與此藥有關的研究，其中一篇表示

that showed that reboxetine was better than placebo,

reboxetine比安慰劑(寬心丸)有效

and I read the other three studies that were published

又有三篇表示

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

reboxetine和其他的抗憂鬱藥效果相當

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

由於其他藥對我的病人幫助不大

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

我就嘗試使用藥效類似的reboxetine

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

結果我被誤導了，事實上

seven trials were conducted comparing reboxetine

在七項比較reboxetine與安慰劑的實驗中

against a dummy placebo sugar pill. One of them

在七項比較reboxetine與安慰劑的實驗中

was positive and that was published, but six of them

只有一個的結果是正面的

were negative and they were left unpublished.

其他六項負面的結果都沒被公布

Three trials were published comparing reboxetine

有三項顯示reboxetine

against other antidepressants in which reboxetine

與其他抗憂鬱劑效果相當的實驗結果被公布

was just as good, and they were published,

與其他抗憂鬱劑效果相當的實驗結果被公布

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

但有三倍的病例顯示reboxetine的效果

which showed that reboxetine was worse than

不如其他治療方式

those other treatments, and those trials were not published.

這些結果也並未被公布

I felt misled.

我覺得被誤導了

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

你或許認為這只是少數極端的例子

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

我也不想斷章取義，只挑有利的資料

cherry-picking and selective referencing

我也不想斷章取義，只挑有利的資料

that I'm accusing other people of.

藉此指控他人

But it turns out that this phenomenon of publication bias

但後來發現其實有很多人

has actually been very, very well studied.

研究這種偏頗的出版取向

So here is one example of how you approach it.

我舉個例子解釋

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

最常見的方式即是蒐集大量

you know that they've been conducted and completed,

完整的實驗結果

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

然後查明他們是否出現在學術文章中

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

現在這裡是十五年來所有

that had ever been conducted on antidepressants

與抗憂鬱劑有關的實驗

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

全都經過FDA認可

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

他們把所有FDA有列入的試驗劃為一組

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

所以並不是每個試驗都有列入

because we can never know if we have those,

因為我們無從得知他人的實驗計畫

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

但所選的實驗結果是為了上市而檢驗

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

接著我們得看看這些結果是否有公布

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

在同儕審查的學術文章中，這是我們發現的

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

一半的結果顯示有效，一半顯示無效

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

兩者其實差距不大

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

但我們在同儕審查的期刊中找到的試驗結果

what they found was a very different picture.

卻是相當不同

Only three of the negative trials were published,

只有三個負面結果被公布

but all but one of the positive trials were published.

正面結果中只有一個沒被公布

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

如果我們快速切換兩者

you can see what a staggering difference there was

你會發現事實與醫生、病患、

between reality and what doctors, patients,

醫療行政人員透過同儕審查的期刊

commissioners of health services, and academics

所得知的資訊有著天壤之別

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

所得知的資訊有著天壤之別

We were misled, and this is a systematic flaw

我們都被誤導了，在醫藥界中

in the core of medicine.

這是一個深入核心的體制問題

In fact, there have been so many studies conducted on

事實上現在有很多研究

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

旨在研究這種出版偏向

collected in a systematic review, published in 2010,

在2010年公布的一項系統性調查中

that took every single study on publication bias

每一個研究出版取向的研究

that they could find.

加起來總共超過一百多項

Publication bias affects every field of medicine.

整個醫療界會徹底的受影響

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

平均多達一半的試驗都從而消失了

and we know that positive findings are around twice as likely

正面試驗結果被公布的機率

to be published as negative findings.

比負面結果高了近兩倍

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

在講究根據為重的醫藥界裡是一個弊端

If I flipped a coin 100 times but then

如果我把一個硬幣拋擲一百次

withheld the results from you from half of those tosses,

但只告訴你一半的結果

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

我就能讓你以為每次投擲都是正面

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

但並不表是硬幣的兩面都是正面

That would mean that I was a chancer

這只表示我是個投機者

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

而你是個白癡，因為你讓我得過且過(笑聲)

But this is exactly what we blindly tolerate

但在已根據為重的醫藥界裡

in the whole of evidence-based medicine.

我們卻盲目縱容

And to me, this is research misconduct.

對我來說，這是研究上的誤導缺失

If I conducted one study and I withheld

如果我進行了一個研究

half of the data points from that one study,

並保留一半的研究結果不公布

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

你會義正嚴詞地指控我研究詐欺

And yet, for some reason, if somebody conducts

但出於某種原因，如果有人做了十項研究

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

卻只公布五個他們想看的結果

we don't consider that to be research misconduct.

我們也不會認為那是誤導研究

And when that responsibility is diffused between

而當責任遍及整體研究員、學術界、

a whole network of researchers, academics,

贊助人、已及期刊編輯時，基於某些原因

industry sponsors, journal editors, for some reason

贊助人已及期刊編輯時，基於某些原因

we find it more acceptable,

我們會認為一切相當合理

but the effect on patients is damning.

但病人卻得承擔這些嚴重的後果

And this is happening right now, today.

這些事情正在發生

This is a drug called Tamiflu. Tamiflu is a drug

這是一種叫Tamiflu的藥

which governments around the world have spent billions

世界各地的政府花了好幾十億資金

and billions of dollars on stockpiling,

貯藏這個藥物

and we've stockpiled Tamiflu in panic,

我們慌忙貯藏此藥的原因乃因

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

此藥被認為能夠減少流感的併發症

Complications is a medical euphemism for pneumonia

併發症說穿了就是肺炎

and death. (Laughter)

和死路一條(笑聲)

Now when the Cochrane systematic reviewers

現在Cochrane的系統審查員正試圖

were trying to collect together all of the data from all

蒐集所有測試Tamiflu用途的實驗

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

蒐集所有測試Tamiflu用途的實驗

they found that several of those trials were unpublished.

他們發現有幾個試驗並未公布

The results were unavailable to them.

試驗結果也無從取得

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

當他們透過不同管道，透過資訊透明法案

through Freedom of Information Act requests, through

並騷擾各個不同單位後

harassing various different organizations, what they found was inconsistent.

他們發現結果互相矛盾

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

在他們試圖取得長達一萬多頁

the 10,000-page long documents that have

並付有清晰完整的臨床研究報告時

the best possible rendition of the information,

並付有清晰完整的臨床研究報告時

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

卻無法取得

And if you want to read the full correspondence

若你想查看藥廠完整的

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

信件內容、藉口、和解釋的話

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

可以去翻翻這星期的PLOS Medicine期刊

of PLOS Medicine.

可以去翻翻這星期的PLOS Medicine期刊

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

整件事中最令我無法置信的是

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

這不只是一個單純的問題，我們雖然知道

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

這是個問題，卻還得裝作問題已解決

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

我們逼人們假裝這個問題已解決

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

首先我們讓各方註冊試驗結果

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

各方會先提出實驗草案

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

事先告知實驗內容

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

之後我們就能查明

have been conducted and completed have been published.

是否所有完整的實驗結果都有透明化

But people didn't bother to use those registers.

但人們並沒有乖乖來註冊

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

國際醫療期刊委員會就上前

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

表示他們會守住防線

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

並不會公布任何未經註冊的實驗結果

unless they've been registered before they began.

並不會公布任何未經註冊的實驗結果

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

但他們並未履行責任，2008年一項研究發現

which showed that half of all of trials published by journals

國際醫療委員會編審的期刊中

edited by members of the ICMJE

一半以上的實驗結果

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

並未正式註冊，有四分之一甚至未經註冊

And then finally, the FDA Amendment Act was passed

直到最後，幾年前FDA修正案終於通過

a couple of years ago saying that everybody who conducts

並規定所有實驗的結果

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

必須在實驗結束一年內公布

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

而2012年BMJ中，一月的第一期版本中

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

有項研究，研究人們是否依然遵循規定

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

結果顯示五人中只有人有做到

have done so.

結果顯示五人中只有一人有做到

This is a disaster.

這是個災難

We cannot know the true effects of the medicines

若我們無法取得所有資訊

that we prescribe if we do not have access

就無從得知處方藥物的實效

to all of the information.

就無從得知處方藥物的實效

And this is not a difficult problem to fix.

而這並不難解決

We need to force people to publish all trials

我們必須強迫人們公布

conducted in humans, including the older trials,

所有人體實驗，包括舊有的試驗

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

因為FDA修正案指要求公布2008之後的試驗

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

我搞不懂為何我們只能

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

根據兩年內的研究資料進行醫療

We need to publish all trials in humans,

所有與人體有關的實驗都得公布

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

先前的實驗和現用的藥物也是

and you need to tell everyone you know

你必須告訴所有認識的人

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

這是一個尚未解決的問題

Thank you very much. (Applause)

謝謝! (掌聲)

(Applause)

(掌聲)