Hi. So, this chap here,

自認可以預知未來

he thinks he can tell you the future.

他的名字是諾斯特拉達姆士，但這張圖看起來

His name is Nostradamus, although here the Sun have

反倒有點像西恩康納瑞

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

我呢，跟大部分的人一樣

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

不太相信人類能預見未來

that people can see into the future.

我不信這套，但你時常會聽到

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

有些人能夠預測未來

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

大概都是僥倖猜中的吧

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

我們也只能聽到這些不尋常的故事

hear about the flukes and about the freaks.

看到人凸槌的機會卻很少

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

我們以為只有預知未來這種事才會出錯

Now we expect that to happen with silly stories

但實際上，

about precognition, but the problem is,

學術界和醫藥界也有同樣的問題

we have exactly the same problem in academia

出錯會賠上人命的

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

現在我們先把焦點放在預知未來上

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

去年有位名叫Daryl Bem的研究員

just last year a researcher called Daryl Bem conducted

做了一項研究，證明大學生

a piece of research where he found evidence

有預測未來的能力

of precognitive powers in undergraduate students,

研究結果收錄在一個同儕審查的學術期刊中

and this was published in a peer-reviewed academic journal

看過的人大部分表示

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

"好吧算他厲害，但這純粹是僥倖猜中，

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

因為我如果做了一個無法證明

that if I did a study where I found no evidence

大學生有預知能力的研究，

that undergraduate students had precognitive powers,

應該就沒有期刊會出版了"

it probably wouldn't get published in a journal.

事實也真的是如此

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

有數個研究團隊試圖

several different groups of research scientists tried

重復這項研究的成果

to replicate the findings of this precognition study,

當他們把結果呈給同樣的出版社時

and when they submitted it to the exact same journal,

出版社表示，"我們對同樣的研究沒興趣，

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

你們的結果與先前的相反，所以我們沒興趣"

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

由此可見，在學術界裡

So this is already evidence of how, in the academic

許多科學研究

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

都存在一種特定偏見

of all of the scientific studies that have been conducted.

這種導向不只出現在心理學研究

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

在癌症的研究中也會出現

It also happens in, for example, cancer research.

2012年三月，也就是一個月前

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

幾位研究員在自然期刊中表示

reported in the journal Nature how they had tried

他們重新做了先前53種治療癌症的基本研究

to replicate 53 different basic science studies looking at

尋找治療癌症的可行方法

potential treatment targets in cancer,

53項研究中，

and out of those 53 studies, they were only able

只有6項成功

to successfully replicate six.

有47項是失敗的

Forty-seven out of those 53 were unreplicable.

討論過程中他們表示，這個結果很可能是因為

And they say in their discussion that this is very likely

不尋常的事物容易備受矚目

because freaks get published.

人們做了一大堆研究

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

成功的實驗結果會被公諸於世

and the occasions when it works they will publish,

失敗的結果不會受到注意

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

這些研究員對這個問題提出解決辦法

And their first recommendation of how to fix this problem,

這個問題將大眾導入迷途

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

他們認為處理這個問題的辦法

their first recommendation of how to fix this problem

即是使失敗的研究結果受到更多重視

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

改變研究動機，鼓勵科學家勇於

and to change the incentives so that scientists are

公布失敗的結果

encouraged to post more of their negative results in public.

這不只發生在臨床基本癌症研究

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.

這也發生在活生生的學術醫藥中

It also happens in the very real, flesh and blood

1980年幾位研究員

of academic medicine. So in 1980,

對一種叫lorcainide的藥物做研究

some researchers did a study on a drug called lorcainide,

這是一種抗心律失常藥

and this was an anti-arrhythmic drug,

用來抑制異常的心搏

a drug that suppresses abnormal heart rhythms,

病人心臟病發後

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

很有可能心律不整

they're quite likely to have abnormal heart rhythms,

若給病人能夠抑制異常心搏的藥

so if we give them a drug that suppresses abnormal heart

便能提高存活率

rhythms, this will increase the chances of them surviving.

初期試用階段，他們對一百多名病患

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

做了一個試驗

just under a hundred patients.

五十名服用lorcainide的患者中，有十人死亡

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

另外五十名服用單純糖做的藥丸

Another 50 patients got a dummy placebo sugar pill

只有一個人死亡

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

他們馬上認定這是個失敗的藥物

So they rightly regarded this drug as a failure,

廣告活動也停止宣傳

and its commercial development was stopped, and because

因為如此，試驗結果也從未公布

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

不幸的是，五年、十年過後

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

其他藥廠開發了同樣能

other companies had the same idea about drugs that would

抑制心臟病患異常心搏的藥

prevent arrhythmias in people who have had heart attacks.

這些藥在市面販售，又因為心臟疾病普遍

These drugs were brought to market. They were prescribed

這些藥經常變成處方藥物

very widely because heart attacks are a very common thing,

我們花了很久的時間才發現

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

這些藥物會提高死亡率

also caused an increased rate of death

在我們發覺這些危險前

that before we detected that safety signal,

美國有十萬人因服用抗心律失常藥而白白送命

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.

而在1993年

Now actually, in 1993,

1980年做過早期試驗的那批研究員

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

發表了一篇悔過書，向科學界致歉

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

他們表示 "1980年進行lorcainide試驗時，

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

我們以為死亡率的提升只是巧合"

we thought that the increased death rate that occurred

我們以為死亡率的提升只是機率問題"

in the lorcainide group was an effect of chance."

基於商業因素，lorcainide停止研發

The development of lorcainide was abandoned for commercial reasons,

這項試驗結果也從未公布

and this study was never published;

由此可見出版業的偏見

it's now a good example of publication bias.

也就是不起眼的資訊常遭到封殺

That's the technical term for the phenomenon where

不是被埋沒就是沒下文

unflattering data gets lost, gets unpublished, is left

他們表示，這個結果"原本有可能做為警惕"

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."

以上只是基層科學方面的故事

Now these are stories from basic science.

而且距今也二、三十年了

These are stories from 20, 30 years ago.

現今的學術出版業已截然不同

The academic publishing environment is very different now.

有一個叫Trials(實驗)的公開期刊

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

收錄各種與人體有關的實驗結果

which will publish any trial conducted in humans

結果是好是壞都會被收錄

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

但失敗的實驗結果仍普遍遭到隱埋

But this problem of negative results that go missing in action

事實上這種情況甚至影響到

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

講究科學根據為重的藥物研發

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

這是一種叫rebozetine的藥

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

我曾把這種藥物開做處方，對抗憂鬱症

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

身為一個菜鳥醫生，我竭盡所能的查詢

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

與此藥有關的研究，其中一篇表示

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

reboxetine比安慰劑(寬心丸)有效

that showed that reboxetine was better than placebo,

又有三篇表示

and I read the other three studies that were published

reboxetine和其他的抗憂鬱藥效果相當

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

由於其他藥對我的病人幫助不大

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

我就嘗試使用藥效類似的reboxetine

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

結果我被誤導了，事實上

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

在七項比較reboxetine與安慰劑的實驗中

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

只有一個的結果是正面的

was positive and that was published, but six of them

其他六項負面的結果都沒被公布

were negative and they were left unpublished.

有三項顯示reboxetine

Three trials were published comparing reboxetine

與其他抗憂鬱劑效果相當的實驗結果被公布

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,

但有三倍的病例顯示reboxetine的效果

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

不如其他治療方式

which showed that reboxetine was worse than

這些結果也並未被公布

those other treatments, and those trials were not published.

我覺得被誤導了

I felt misled.

你或許認為這只是少數極端的例子

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

我也不想斷章取義，只挑有利的資料

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

藉此指控他人

that I'm accusing other people of.

但後來發現其實有很多人

But it turns out that this phenomenon of publication bias

研究這種偏頗的出版取向

has actually been very, very well studied.

我舉個例子解釋

So here is one example of how you approach it.

最常見的方式即是蒐集大量

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

完整的實驗結果

you know that they've been conducted and completed,

然後查明他們是否出現在學術文章中

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

現在這裡是十五年來所有

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

與抗憂鬱劑有關的實驗

that had ever been conducted on antidepressants

全都經過FDA認可

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

他們把所有FDA有列入的試驗劃為一組

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

所以並不是每個試驗都有列入

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

因為我們無從得知他人的實驗計畫

because we can never know if we have those,

但所選的實驗結果是為了上市而檢驗

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

接著我們得看看這些結果是否有公布

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

在同儕審查的學術文章中，這是我們發現的

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

一半的結果顯示有效，一半顯示無效

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

兩者其實差距不大

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

但我們在同儕審查的期刊中找到的試驗結果

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

卻是相當不同

what they found was a very different picture.

只有三個負面結果被公布

Only three of the negative trials were published,

正面結果中只有一個沒被公布

but all but one of the positive trials were published.

如果我們快速切換兩者

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

你會發現事實與醫生、病患、

you can see what a staggering difference there was

醫療行政人員透過同儕審查的期刊

between reality and what doctors, patients,

所得知的資訊有著天壤之別

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.

我們都被誤導了，在醫藥界中

We were misled, and this is a systematic flaw

這是一個深入核心的體制問題

in the core of medicine.

事實上現在有很多研究

In fact, there have been so many studies conducted on

旨在研究這種出版偏向

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

在2010年公布的一項系統性調查中

collected in a systematic review, published in 2010,

每一個研究出版取向的研究

that took every single study on publication bias

加起來總共超過一百多項

that they could find.

整個醫療界會徹底的受影響

Publication bias affects every field of medicine.

平均多達一半的試驗都從而消失了

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

正面試驗結果被公布的機率

and we know that positive findings are around twice as likely

比負面結果高了近兩倍

to be published as negative findings.

在講究根據為重的醫藥界裡是一個弊端

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

如果我把一個硬幣拋擲一百次

If I flipped a coin 100 times but then

但只告訴你一半的結果

withheld the results from you from half of those tosses,

我就能讓你以為每次投擲都是正面

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

但並不表是硬幣的兩面都是正面

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

這只表示我是個投機者

That would mean that I was a chancer

而你是個白癡，因為你讓我得過且過(笑聲)

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

但在已根據為重的醫藥界裡

But this is exactly what we blindly tolerate

我們卻盲目縱容

in the whole of evidence-based medicine.

對我來說，這是研究上的誤導缺失

And to me, this is research misconduct.

如果我進行了一個研究

If I conducted one study and I withheld

並保留一半的研究結果不公布

half of the data points from that one study,

你會義正嚴詞地指控我研究詐欺

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

但出於某種原因，如果有人做了十項研究

And yet, for some reason, if somebody conducts

卻只公布五個他們想看的結果

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

我們也不會認為那是誤導研究

we don't consider that to be research misconduct.

而當責任遍及整體研究員、學術界、

And when that responsibility is diffused between

贊助人、已及期刊編輯時，基於某些原因

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

我們會認為一切相當合理

we find it more acceptable,

但病人卻得承擔這些嚴重的後果

but the effect on patients is damning.

這些事情正在發生

And this is happening right now, today.

這是一種叫Tamiflu的藥

This is a drug called Tamiflu. Tamiflu is a drug

世界各地的政府花了好幾十億資金

which governments around the world have spent billions

貯藏這個藥物

and billions of dollars on stockpiling,

我們慌忙貯藏此藥的原因乃因

and we've stockpiled Tamiflu in panic,

此藥被認為能夠減少流感的併發症

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

併發症說穿了就是肺炎

Complications is a medical euphemism for pneumonia

和死路一條(笑聲)

and death. (Laughter)

現在Cochrane的系統審查員正試圖

Now when the Cochrane systematic reviewers

蒐集所有測試Tamiflu用途的實驗

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,

他們發現有幾個試驗並未公布

they found that several of those trials were unpublished.

試驗結果也無從取得

The results were unavailable to them.

當他們透過不同管道，透過資訊透明法案

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

並騷擾各個不同單位後

through Freedom of Information Act requests, through

他們發現結果互相矛盾

harassing various different organizations, what they found was inconsistent.

在他們試圖取得長達一萬多頁

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

並付有清晰完整的臨床研究報告時

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,

卻無法取得

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

若你想查看藥廠完整的

And if you want to read the full correspondence

信件內容、藉口、和解釋的話

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

可以去翻翻這星期的PLOS Medicine期刊

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.

整件事中最令我無法置信的是

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

這不只是一個單純的問題，我們雖然知道

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

這是個問題，卻還得裝作問題已解決

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

我們逼人們假裝這個問題已解決

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

首先我們讓各方註冊試驗結果

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

各方會先提出實驗草案

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

事先告知實驗內容

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