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

Translator: Joseph Geni Reviewer: Morton Bast

Prevodilac: Tatjana Jevdjic Lektor: Jelena Nedjic

Hi. So, this chap here,

Zdravo. Dakle, ovaj momak

he thinks he can tell you the future.

misli da može predvideti vašu budućnost.

His name is Nostradamus, although here the Sun have

Zove se Nostradamus, a časopis "Sunce" ga je

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

prikazao tako da podseća na Šona Konerija. (Smeh)

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

Pretpostavljam da većina vas, kao i ja

that people can see into the future.

ne veruje da ljudi mogu videti budućnost.

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

Ne verujem u vidovitost, ali povremeno

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

čujete da neko može da predvidi događaje u budućnosti,

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

to je verovatno samo slučajnost, a mi samo

hear about the flukes and about the freaks.

čujemo o slučajnostima i odstupanjima.

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

Ne čujemo o svim onim situacijama kada su oni pogrešili.

Now we expect that to happen with silly stories

Mi očekujemo da se to dogodi u smešnim

about precognition, but the problem is,

slučajevima vidovitosti, ali problem je

we have exactly the same problem in academia

što se sa time nosimo i u nauci

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

i u medicini, a u tim okolnostima, plaća se životima.

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

Prvo, razmišljajući samo o vidovitosti,

just last year a researcher called Daryl Bem conducted

prošle godine je istraživač Deril Bem sproveo

a piece of research where he found evidence

istraživanje u kom je došao do dokaza

of precognitive powers in undergraduate students,

o postojanju vidovitosti kod studenata.

and this was published in a peer-reviewed academic journal

To je objavljeno u naučnom časopisu,

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

a većina ljudi koja je to pročitala jednostavno je rekla:

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

“OK, ali mislim da je to slučajnost, to je odstupanje jer znam

that if I did a study where I found no evidence

da ako bih ja uradio studiju koja ne dokazuje

that undergraduate students had precognitive powers,

postojanje vidovitosti studenata,

it probably wouldn't get published in a journal.

ona verovatno ne bi bila objavljena.”

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

U stvari, znamo da je to tačno

several different groups of research scientists tried

jer je nekoliko različitih grupa istraživača pokušalo

to replicate the findings of this precognition study,

da ponovi nalaze ove studije o vidovitosti,

and when they submitted it to the exact same journal,

a kada su ih predali istom tom časopisu,

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

dobili su odgovor: “Ne, nismo zainteresovani za ponovljenu

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

studiju. Nismo zainteresovani za vaš negativan rezultat.”

So this is already evidence of how, in the academic

Već ovo je dokaz kako u naučnoj

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

literaturi možemo videti pogrešan uzorak stvarne slike

of all of the scientific studies that have been conducted.

svih naučnih studija koje su sprovedene.

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

Ovo se ne dešava samo u akademskom izučavanju psihologije.

It also happens in, for example, cancer research.

Na primer, ovo se takođe dešava u istraživanju karcinoma.

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

Tako su pre samo mesec dana, u martu 2012. neki istraživači

reported in the journal Nature how they had tried

objavili u časopisu "Nature" kako su pokušali

to replicate 53 different basic science studies looking at

da ponove 53 različite studije bazičnih nauka koje su

potential treatment targets in cancer,

proučavale moguće ciljeve terapije karcinoma

and out of those 53 studies, they were only able

i od te 53 studije, mogli su uspešno

to successfully replicate six.

da ponove šest.

Forty-seven out of those 53 were unreplicable.

Četrdeset i sedam od ovih 53 nisu mogli da ponove.

And they say in their discussion that this is very likely

U diskusiji su tvrdili da je to verovatno

because freaks get published.

jer se odstupanja objavljuju.

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

Ljudi će uraditi mnogo i mnogo različitih studija,

and the occasions when it works they will publish,

uspešni slučajevi će biti objavljeni,

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

a neuspešni neće.

And their first recommendation of how to fix this problem,

Njihova prva preporuka kako da rešimo ovaj problem,

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

a to jeste problem, jer nas sve šalje niz slepe ulice,

their first recommendation of how to fix this problem

njihova prva preporuka kako rešiti ovaj problem je

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

da se olakša objavljivanje negativnih naučnih rezultata

and to change the incentives so that scientists are

i da se promene motivi tako da ohrabe

encouraged to post more of their negative results in public.

naučnike da objave veći broj negativnih rezultata.

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

Ovo se ne događa samo u veoma izolovanoj oblasti

of preclinical basic science cancer research.

prekliničkih bazičnih istraživanja karcinoma.

It also happens in the very real, flesh and blood

Takođe se događa u veoma stvarnoj, od krvi i mesa

of academic medicine. So in 1980,

oblasti naučne medicine. Tako su 1980.

some researchers did a study on a drug called lorcainide,

neki istraživači proučavali lek lorkainid,

and this was an anti-arrhythmic drug,

koji je antiaritmik

a drug that suppresses abnormal heart rhythms,

i suzbija nepravilan srčani ritam,

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

a ideja je bila da će ljudi, nakon doživljenog srčanog udara,

they're quite likely to have abnormal heart rhythms,

vrlo verovatno patiti od nepravilnog srčanog ritma,

so if we give them a drug that suppresses abnormal heart

pa ako im se da lek koji sprečava poremećaj srčane

rhythms, this will increase the chances of them surviving.

ritmike, povećaće se verovatnoća njihovog preživljavanja.

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

Na početku njegovog razvoja, uradili su veoma malu studiju,

just under a hundred patients.

uključujući manje od sto pacijenata.

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

Pedeset pacijenata je dobilo lorkainid i 10 je umrlo.

Another 50 patients got a dummy placebo sugar pill

Drugih 50 je dobilo praznu placebo zašećernu tabletu

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

bez aktivnog sastojka i samo jedan je umro.

So they rightly regarded this drug as a failure,

Dakle, ispravno su zaključili da je lek neuspešan,

and its commercial development was stopped, and because

njegov komercijalni razvoj je zaustavljen, a zbog tog

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

zaustavljanja, ispitivanje nikad nije bilo objavljeno.

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

Nažalost, tokom narednih 5 godina, 10 godina,

other companies had the same idea about drugs that would

druge kompanije su došle na istu ideju o lekovima koji bi

prevent arrhythmias in people who have had heart attacks.

sprečili aritmije kod ljudi koji su doživeli srčani udar.

These drugs were brought to market. They were prescribed

Ovi lekovi su izašli na tržište. Oni su prepisivani

very widely because heart attacks are a very common thing,

dosta često jer su infarkti srca česti

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

i trebalo nam je dosta vremena da otkrijemo da ovi lekovi

also caused an increased rate of death

takođe povećavaju smrtnost,

that before we detected that safety signal,

tako da je, pre nego što smo otkrili znak za uzbunu,

over 100,000 people died unnecessarily in America

preko 100 000 ljudi u Americi nepotrebno umrlo

from the prescription of anti-arrhythmic drugs.

zbog prepisivanja antiaritmika.

Now actually, in 1993,

U stvari, 1993.

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

istraživači koji su uradili studiju 1980. - tu početnu studiju,

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

objavili su je kao mea culpa, izvinjenje naučnoj zajednici

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

u kom su izjavili: “Kada smo radili studiju 1980.,

we thought that the increased death rate that occurred

mislili smo da je povećana smrtnost

in the lorcainide group was an effect of chance."

u lorkainid grupi slučajnost.”

The development of lorcainide was abandoned for commercial reasons,

Razvoj lorkainida je napušten iz komercijalnih razloga

and this study was never published;

i ova studija nikad nije objavljena;

it's now a good example of publication bias.

sada je to dobar primer pristrasnosti objavljivanja.

That's the technical term for the phenomenon where

To je tehnički izraz za pojavu kada

unflattering data gets lost, gets unpublished, is left

neželjeni podaci budu izgubljeni, ostanu neobjavljeni,

missing in action, and they say the results described here

izgube se u akciji i oni tvrde da su ovde opisani rezultati

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

“mogli da obezbede rano upozorenje na problem”.

Now these are stories from basic science.

Ovo su priče iz bazičnih nauka.

These are stories from 20, 30 years ago.

Ovo su priče od pre 20, 30 godina.

The academic publishing environment is very different now.

Naučno izdavačko okruženje je danas veoma različito.

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

Postoje naučni časopisi kao što je “Trials”, časopis slobodnog pristupa,

which will publish any trial conducted in humans

koji će objaviti svako ispitivanje sprovedeno na ljudima

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

nezavisno od toga da li je ishod pozitivan ili negativan.

But this problem of negative results that go missing in action

Ali ovaj problem negativnih rezultata izgubljenih u akciji

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

je i dalje veoma prisutan. U stvari toliko je prisutan,

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

da je u samom centru medicine koja je zasnovana na dokazima.

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

Ovo je lek nazvan reboksetin, taj lek

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

sam i ja prepisivao. On je antidepresiv.

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

Ja sam doktor štreber, tako da sam pročitao sve moguće

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

studije o ovom leku. Pročitao sam jednu objavljenu studiju

that showed that reboxetine was better than placebo,

koja je pokazala da je reboksetin bolji od placeba

and I read the other three studies that were published

i još tri studije koje su objavljene,

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

a pokazale su da je dobar koliko i drugi antidepresivi

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

i budući da ovaj pacijent nije dobro odreagovao na druge antidepresive,

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

pomislio sam, reboksetin je jednako dobar. Mogu da pokušam.

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

Ali se ispostavilo da sam bio obmanut. U stvari,

seven trials were conducted comparing reboxetine

sedam ispitivanja je sprovedeno poredeći reboksetin

against a dummy placebo sugar pill. One of them

sa lažnom placebo šećernom tabletom. Jedna od njih

was positive and that was published, but six of them

je bila pozitivna i ta je objavljena, ali šest ostalih

were negative and they were left unpublished.

su bile negativne i nisu objavljene.

Three trials were published comparing reboxetine

Objavljena su tri ispitivanja, koja porede reboksetin

against other antidepressants in which reboxetine

sa drugim antidepresivima, u kojima je reboksetin

was just as good, and they were published,

podjednako dobar,

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

ali tri puta više valjanih podataka o pacijentima je sakupljeno,

which showed that reboxetine was worse than

a oni pokazuju da je reboksetin lošiji

those other treatments, and those trials were not published.

od tih drugih lekova i ova ispitivanja nisu objavljena.

I felt misled.

Osećao sam se obmanuto.

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

Sada vi možete reći, pa dobro, to je veoma neobičan primer

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

i ne bih želeo da budem kriv za istu vrstu

cherry-picking and selective referencing

probiranja i selektivnog obaveštavanja

that I'm accusing other people of.

za koje optužujem druge ljude.

But it turns out that this phenomenon of publication bias

Ali proizlazi da je ova pojava izdavačke pristrasnosti,

has actually been very, very well studied.

zapravo bila veoma, veoma dobro proučavana.

So here is one example of how you approach it.

Ovde je jedan primer kako da joj pristupite.

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

Klasični model je, dobijete grupu studija za koje

you know that they've been conducted and completed,

znate da su bile sprovedene i završene,

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

a zatim proverite da li su igde objavljene

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

u naučnoj literaturi. Znači, ovim pristupom su uzeta

that had ever been conducted on antidepressants

sva ikad sprovedena ispitivanja o antidepresivima,

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

a odobrila ih je FDA tokom 15 godina.

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

Uzeli su sva ispitivanja koja su predata u FDA kao deo paketa za saglasnost.

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

Dakle, to nisu sva ispitivanja o ovim lekovima koja su ikad sprovedena

because we can never know if we have those,

jer nikad ne možemo znati da imamo sva ispitivanja,

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

ali to su ona koja su sprovedena da bi se dobila dozvola za proizvodnju.

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

A zatim su proverili da li su ova ispitivanja objavljena

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

u kritički pregledanoj naučnoj literaturi. Ovo su pronašli.

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

To je podela gotovo pola-pola. Stvarno, polovina ovih

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

ispitivanja je bila pozitivna, polovina negativna.

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

Ali kada su tražili ova ispitivanja u naučnoj literaturi,

what they found was a very different picture.

dobili su veoma različitu sliku.

Only three of the negative trials were published,

Samo tri negativna ispitivanja su bila objavljena,

but all but one of the positive trials were published.

ali sva pozitivna ispitivanja, izuzev jednog, bila su objavljena.

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

Ako ih sada samo rasvetlimo

you can see what a staggering difference there was

možete uvideti upadljivu razliku koja postoji

between reality and what doctors, patients,

između stvarnosti i onoga što lekari, pacijenti,

commissioners of health services, and academics

zastupnici zdravstvene službe i naučnici

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

mogu da vide u kritički pregledanoj naučnoj literaturi.

We were misled, and this is a systematic flaw

Mi smo obmanuti i ovo je sistemska mana

in the core of medicine.

u samoj srži medicine.

In fact, there have been so many studies conducted on

U stvari, postojalo je veoma mnogo studija urađenih o

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

pristrasnosti izdavaštva, preko sto, tako da su one

collected in a systematic review, published in 2010,

sakupljene u sistematskom prikazu objavljenom 2010.

that took every single study on publication bias

Uzeli su svaku studiju o pristrasnosti izdavaštva

that they could find.

koju su mogli da pronađu.

Publication bias affects every field of medicine.

Pristrasnost objavljivanja utiče na svaki deo medicine.

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

Prosečno oko polovina svih ispitivanja se izgubi u akciji,

and we know that positive findings are around twice as likely

a mi znamo da će pozitivni nalazi biti dva puta

to be published as negative findings.

češće objavljeni nego negativni.

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

Ovo je rak u srži medicine zasnovane na dokazima.

If I flipped a coin 100 times but then

Ukoliko 100 puta bacim novčić, ali zatim

withheld the results from you from half of those tosses,

uskratim razultate polovine ovih bacanja,

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

izgledalo bi da imam novčić koji uvek pokazuje glavu.

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

Ali ovo ne bi značilo da imam novčić sa dve glave.

That would mean that I was a chancer

To bi značilo da sam oportunista,

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

i da ste vi glupi što ste mi dozvolili da se sa tim izvučem. (Smeh)

But this is exactly what we blindly tolerate

Ali ovo je upravo ono što slepo dopuštamo

in the whole of evidence-based medicine.

u celokupnoj medicini zasnovanoj na dokazima.

And to me, this is research misconduct.

Za mene, ovo je istraživački prestup.

If I conducted one study and I withheld

Ukoliko sam sproveo jednu studiju i uskratio

half of the data points from that one study,

polovinu podataka iz jedne studije,

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

vi biste me ispravno optužili za istraživačku prevaru.

And yet, for some reason, if somebody conducts

Ali iz nekog razloga ako neko sprovede

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

10 studija, ali objavi samo pet koje su dale rezultat koji su želeli,

we don't consider that to be research misconduct.

ne smatramo da je to istraživački prestup.

And when that responsibility is diffused between

A kada se ta odgovornost raspline u

a whole network of researchers, academics,

celoj mreži istraživača, naučnika,

industry sponsors, journal editors, for some reason

privrednih sponzora, urednika časopisa, iz nekog razloga

we find it more acceptable,

mislimo da je prihvatljivija,

but the effect on patients is damning.

ali efekat je sudbinski za pacijente.

And this is happening right now, today.

Ovo se upravo sada događa, danas.

This is a drug called Tamiflu. Tamiflu is a drug

Ovo je lek nazvan Tamiflu. Tamiflu je lek

which governments around the world have spent billions

na koji su vlade sveta potrošile milijarde i

and billions of dollars on stockpiling,

milijarde dolara da bi stvorili zalihe

and we've stockpiled Tamiflu in panic,

i napravili smo zalihe Tamiflua u panici,

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

verujući da će smanjiti učestalost komplikacija gripa.

Complications is a medical euphemism for pneumonia

Komplikacije su medicinski eufemizam za upalu pluća

and death. (Laughter)

i smrt. (Smeh)

Now when the Cochrane systematic reviewers

Kada su istraživači Kokranove biblioteke

were trying to collect together all of the data from all

pokušali da sakupe sve podatke iz svih istraživanja

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

koja su ikad sprovedena radi provere da li Tamiflu ima taj efekat ili ne,

they found that several of those trials were unpublished.

pronašli su da nekoliko ispitivanja nije objavljeno.

The results were unavailable to them.

Ovi rezultati su im bili nedostupni.

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

A kada su počeli da dolaze do zapisa iz ovih ispitivanja, različitim putevima,

through Freedom of Information Act requests, through

preko Zakona o slobodi informacija,

harassing various different organizations, what they found was inconsistent.

uznemiravanjem različitih organizacija, našli su protivurečnosti.

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

Kada su pokušali da uzmu izveštaje kliničkih studija,

the 10,000-page long documents that have

to su dokumenti dugi 10 000 stranica koji

the best possible rendition of the information,

sadrže najbolje predstavljene informacije,

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

rečeno im je da nemaju dozvolu za njih.

And if you want to read the full correspondence

Ukoliko želite da pročitate potpunu prepisku,

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

opravdanja i objašnjenja koja je dala farmaceutska kompanija,

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

možete da ih vidite u ovonedeljnom izdanju

of PLOS Medicine.

časopisa PLOS Medicine.

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

Ono što mene od svega najviše zbunjuje je

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

da ovo nije samo problem koji prepoznajemo

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

nego što moramo da trpimo lažna rešenja.

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

Ljudi su se pretvarali da je ovaj problem rešen.

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

Prvo, imali smo registar ispitivanja i svi su tvrdili

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

oh, to je dobro. Svako će prijaviti svoja ispitivanja, poslaće protokol,

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

reći će šta će šta želi da uradi pre nego što počne,

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

a posle ćemo moći da vidimo i proverimo da li su sva sprovedena

have been conducted and completed have been published.

i završena ispitivanja objavljena.

But people didn't bother to use those registers.

Ali, ljudi se nisu zamarali upotrebom tih registara.

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

Zatim se pojavio Internacionalni odbor urednika medicinskih časopisa

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

koji je tvrdio da će oni biti čuvari.

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

"Nećemo objavljivati nijedan časopis i nijedno ispitivanje

unless they've been registered before they began.

ukoliko nije bilo prijavljeno pre nego što je započeto."

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

Ali nisu izdržali. 2008. sprovedena je studija

which showed that half of all of trials published by journals

koja je pokazala da polovina ispitivanja objavljenih u časopisima,

edited by members of the ICMJE

koje su uređivali članovi Odbora,

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

nije bila pravilno prijavljena, a četvrtina uopšte nije bila prijavljena.

And then finally, the FDA Amendment Act was passed

Konačno, pre nekoliko godina

a couple of years ago saying that everybody who conducts

usvojen je FDA amandman koji traži da svako ko sprovodi

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

ispitivanje mora da dostavi rezultate u roku od godinu dana.

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

U BMJ, u prvom izdanju iz januara 2012.,

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

možete da vidite studiju koja proverava da li su se

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

istraživači pridržavali ove odluke i proizlazi da

have done so.

samo jedan od pet jeste.

This is a disaster.

Ovo je katastrofa.

We cannot know the true effects of the medicines

Ne možemo da znamo prave efekte lekova

that we prescribe if we do not have access

koje prepisujemo ako nemamo pristup

to all of the information.

svim informacijama.

And this is not a difficult problem to fix.

A ovaj problem nije teško rešiti.

We need to force people to publish all trials

Moramo da nateramo istraživače da objavljuju sva ispitivanja

conducted in humans, including the older trials,

sprovedena na ljudima, uključujući i ranija ispitivanja

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

jer FDA amandman zahteva objavljivanje ispitivanja samo posle 2008.

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

Ne znam u kakvom svetu živimo, ako

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

lečimo samo na osnovu ispitivanja završenih u poslednje dve godine.

We need to publish all trials in humans,

Moramo da objavimo sva ispitivanja na ljudima,

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

uključujući starija ispitivanja, za sve lekove koji se sad koriste

and you need to tell everyone you know

i morate da obavestite sve koje poznajete

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

da je ovo problem i da nije rešen.

Thank you very much. (Applause)

Hvala vam mnogo. (Aplauz)

(Applause)

(Aplauz)