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

Translator: Joseph Geni Reviewer: Morton Bast

Translator: Silvia Miguélez Reviewer: Servizo de Normalización Lingüística

Ola!

Resulta que este tipo cre que pode predicir o futuro.

Chámase Nostradamus, aínda que aquí en The Sun

paréceselle un pouco ao Sean Connery.

(Risas)

Hi. So, this chap here,

E como a maioría de vós, sospeito, non creo realmente

que a xente poida prever o futuro.

he thinks he can tell you the future.

Non creo na precognición e, cando ás veces

His name is Nostradamus, although here the Sun have

escoitas que alguén foi quen de predicir algo que pasou no futuro,

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

probablemente fose unha casualidade,

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

pero só escoitamos falar das casualidades e da sorte.

that people can see into the future.

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

Non sabemos todas as veces que errou esta xente.

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

Se ben esperamos que isto ocorra coas historias parvas sobre precognición,

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

o caso é que temos o mesmo problema

hear about the flukes and about the freaks.

no mundo académico e na medicina,

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

e, nese contexto, custa vidas.

Now we expect that to happen with silly stories

about precognition, but the problem is,

Falando da precognición,

resulta que, o pasado ano, o investigador Daryl Bem

we have exactly the same problem in academia

realizou un estudo no que achou probas

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

de poderes precognitivos en estudantes universitarios,

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

e isto publicouse nunha revista académica revisada por pares.

just last year a researcher called Daryl Bem conducted

A maioría da xente que o leu dixo:

“Vale, pero creo que tiveron sorte, porque sei

a piece of research where he found evidence

que se eu fixese un estudo no que non atopase probas

of precognitive powers in undergraduate students,

de que os estudantes teñen poderes precognitivos,

and this was published in a peer-reviewed academic journal

probablemente non se publicaría nunha revista.”

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

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

De feito, sabemos que é verdade,

that if I did a study where I found no evidence

porque varios grupos diferentes de investigadores

that undergraduate students had precognitive powers,

intentaron replicar os achados deste estudo de precognición

it probably wouldn't get published in a journal.

e, ao presentalo á mesma revista, contestáronlles:

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

“Non estamos interesados en publicar copias nin nos vosos datos negativos.”

several different groups of research scientists tried

to replicate the findings of this precognition study,

Isto xa evidencia como, na literatura académica,

and when they submitted it to the exact same journal,

veremos unha mostra parcial da imaxe real

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

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

de todos os estudos científicos realizados.

So this is already evidence of how, in the academic

Pero non só ocorre no árido campo académico da psicoloxía.

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

Tamén acontece, por exemplo, na investigación do cancro.

of all of the scientific studies that have been conducted.

En marzo do 2012, hai un mes,

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

algúns investigadores informaron na revista Nature

de como intentaran replicar 53 estudos científicos básicos

It also happens in, for example, cancer research.

observando obxectivos potenciais de tratamento do cancro.

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

Destes 53 estudos, só puideron replicar seis con éxito;

reported in the journal Nature how they had tried

to replicate 53 different basic science studies looking at

47 deses 53 non eran reproducibles.

potential treatment targets in cancer,

Na discusión, din que isto pode ser

and out of those 53 studies, they were only able

to successfully replicate six.

porque as casualidades son as que se publican.

Forty-seven out of those 53 were unreplicable.

Fanse moitísimos estudos diferentes.

Cando funcionan, saen publicados

e, cando non funcionan, non.

And they say in their discussion that this is very likely

A súa primeira recomendación para solucionar o problema,

because freaks get published.

porque é un problema que nos envíanos a rúas sen saída,

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

and the occasions when it works they will publish,

a súa primeira recomendación para solucionalo

é facilitar a publicación de resultados negativos na ciencia

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

And their first recommendation of how to fix this problem,

e cambiar os incentivos para animar os científicos

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

a publicar máis dos seus resultados negativos.

their first recommendation of how to fix this problem

Pero isto non só ocorre no árido mundo da investigación preclínica do cancro.

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

and to change the incentives so that scientists are

encouraged to post more of their negative results in public.

Tamén acontece na medicina académica real, de carne e óso.

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

No ano 1980,

of preclinical basic science cancer research.

uns investigadores fixeron un estudo sobre a iorcainida,

un medicamento antiarrítmico,

It also happens in the very real, flesh and blood

que suprime os ritmos cardíacos anormais,

of academic medicine. So in 1980,

e a idea era que, como despois dun ataque cardíaco

é moi probable ter ritmos cardíacos anormais,

some researchers did a study on a drug called lorcainide,

se lles damos algo que suprima ese ritmo anormal,

and this was an anti-arrhythmic drug,

aumentarán as posibilidades de supervivencia.

a drug that suppresses abnormal heart rhythms,

Nos seus comezos, fixeron un ensaio pequeno,

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

con apenas 100 pacientes.

they're quite likely to have abnormal heart rhythms,

Cincuenta pacientes recibiron iorcainida, e dez deles morreron.

so if we give them a drug that suppresses abnormal heart

rhythms, this will increase the chances of them surviving.

Outros 50 recibiron o placebo, unha pílula de azucre

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

sen ingrediente activo, e só un deles morreu,

just under a hundred patients.

así que consideraron este fármaco como un fracaso

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

e detívose o seu desenvolvemento,

e por isto mesmo o ensaio nunca se publicou.

Another 50 patients got a dummy placebo sugar pill

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

Desafortunadamente, ao longo dos seguintes cinco, dez anos,

So they rightly regarded this drug as a failure,

and its commercial development was stopped, and because

outras compañías tiveron a mesma idea sobre fármacos

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

que evitarían arritmias en persoas con ataques cardíacos.

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

Estes fármacos leváronse ao mercado.

Prescribíronse moito, pois os ataques cardíacos son moi comúns,

other companies had the same idea about drugs that would

e tardamos tanto en descubrir que estes fármacos

prevent arrhythmias in people who have had heart attacks.

tamén aumentaban a taxa de mortalidade

These drugs were brought to market. They were prescribed

que, antes de detectar ese problema,

very widely because heart attacks are a very common thing,

máis de 100 000 persoas morreron innecesariamente nos EE. UU.

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

also caused an increased rate of death

por prescrición de medicamentos antiarrítmicos.

that before we detected that safety signal,

De feito, en 1993,

over 100,000 people died unnecessarily in America

os investigadores que fixeran o estudo de 1980

publicaron un mea culpa, unha desculpa á comunidade científica,

from the prescription of anti-arrhythmic drugs.

Now actually, in 1993,

na que dixeron: “Cando fixemos o noso estudo en 1980,

pensamos que o aumento da mortalidade

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

do grupo da iorcainida fora efecto do azar.”

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

O desenvolvemento detívose por razóns comerciais,

e este estudo nunca se publicou; un bo exemplo de nesgo de publicación.

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

we thought that the increased death rate that occurred

Este é o termo técnico para o fenómeno

in the lorcainide group was an effect of chance."

en que os datos desagradables se perden, non se publican, desaparecen

The development of lorcainide was abandoned for commercial reasons,

e, polo que din, os resultados aquí descritos

and this study was never published;

it's now a good example of publication bias.

“poderían proporcionar un aviso de problemas por vir.”

That's the technical term for the phenomenon where

unflattering data gets lost, gets unpublished, is left

Estas son historias de ciencia básica,

missing in action, and they say the results described here

historias de hai 20, 30 anos.

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

O ambiente académico editorial é moi diferente agora.

Now these are stories from basic science.

Hai revistas académicas como Trials, a revista de acceso aberto,

These are stories from 20, 30 years ago.

que publica calquera ensaio feito en humanos,

tivese un resultado positivo ou negativo.

The academic publishing environment is very different now.

Pero este problema de resultados negativos que se abandonan

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

segue sendo moi frecuente.

which will publish any trial conducted in humans

É tan frecuente que afecta ás bases da medicina baseada en probas.

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

But this problem of negative results that go missing in action

Este é un fármaco chamado reboxetina;

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

téñoa prescrito eu mesmo. É un antidepresivo.

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

Son un médico moi estudoso, así que lin todos os estudos que puiden dela.

Lin un estudo publicado

que amosaba que a reboxetina era mellor que o placebo,

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

e tamén outros tres estudos

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

que mostraban que era igual de boa que outros antidepresivos.

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

Como ao paciente non lle foran ben os outros antidepresivos,

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

pensei que podía probar a reboxetina.

that showed that reboxetine was better than placebo,

Pero resulta que me enganaron.

and I read the other three studies that were published

De feito, houbo sete ensaios que comparaban a reboxetina

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

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

cunha pílula de azucre placebo.

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

Un deles foi positivo e publicouse,

pero seis foron negativos e quedaron sen publicar.

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

seven trials were conducted comparing reboxetine

Publicáronse tres ensaios que afirmaban

que era tan boa como outros antidepresivos,

against a dummy placebo sugar pill. One of them

was positive and that was published, but six of them

polo que se publicaron,

pero recolléronse tres veces máis datos de pacientes

were negative and they were left unpublished.

que demostraban que a reboxetina era peor que outros tratamentos,

Three trials were published comparing reboxetine

against other antidepressants in which reboxetine

e estes ensaios non se publicaron.

was just as good, and they were published,

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

Sentinme enganado.

Poderiades dicir que é un exemplo moi pouco habitual,

which showed that reboxetine was worse than

e non me gustaría caer no mesmo tipo

those other treatments, and those trials were not published.

de escolla e referencia selectiva

I felt misled.

das que acuso outras persoas,

pero o fenómeno do nesgo de publicación

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

está máis que estudado.

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

Aquí temos un exemplo de como abordalo.

cherry-picking and selective referencing

O modelo clásico é coller uns cantos estudos

que sabemos que se fixeron e completaron

that I'm accusing other people of.

e logo ver se se publicaron xa na literatura académica.

But it turns out that this phenomenon of publication bias

has actually been very, very well studied.

Isto levou a todos os ensaios

So here is one example of how you approach it.

sobre antidepresivos

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

aprobados pola FDA nun período de 15 anos.

you know that they've been conducted and completed,

Tomaron todos os ensaios presentados á FDA para a súa aprobación.

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

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

Non son todos os ensaios feitos sobre estes fármacos.

that had ever been conducted on antidepressants

Nunca poderemos saber se os temos todos.

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

Son os que se fixeron para obter a autorización de comercialización.

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

Despois, viron se estes ensaios se publicaran

na literatura revisada por pares. Isto é o que descubriron.

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

Había unha división de 50-50.

because we can never know if we have those,

A metade destes ensaios foran positivos e a metade negativos.

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

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

Pero cando buscaron estes ensaios na literatura revisada por pares,

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

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

o que descubriron foi moi diferente:

só tres dos ensaios negativos se publicaran,

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

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

pero publicáranse todos os ensaios positivos menos un.

what they found was a very different picture.

Agora ben, se facemos unha comparativa,

Only three of the negative trials were published,

podedes ver a diferenza asombrosa que había

but all but one of the positive trials were published.

entre a realidade e o que os médicos, os pacientes,

os membros dos servizos de saúde e os académicos

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

puideron ver na literatura académica revisada por pares.

you can see what a staggering difference there was

Enganáronnos, e isto é un defecto sistemático

between reality and what doctors, patients,

na base da medicina.

commissioners of health services, and academics

De feito, fixéronse tantos estudos

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

sobre o nesgo na publicación, máis de 100,

We were misled, and this is a systematic flaw

que se recolleron nunha revisión sistemática publicada no 2010,

in the core of medicine.

con todos os estudos que se atoparon sobre o nesgo na publicación.

In fact, there have been so many studies conducted on

O nesgo na publicación afecta a todos os campos da medicina.

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

Arredor da metade dos ensaios, de media, abandónanse,

collected in a systematic review, published in 2010,

e sabemos que os resultados positivos teñen o dobre de probabilidades

that took every single study on publication bias

that they could find.

de publicarse que os negativos.

Publication bias affects every field of medicine.

Isto é un cancro na base dunha medicina baseada en probas.

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

Se lanzase unha moeda 100 veces,

and we know that positive findings are around twice as likely

pero agochase os resultados da metade dos lanzamentos,

to be published as negative findings.

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

podería facer que parecese que a moeda sempre cae de cara.

Pero non é que a moeda teña dúas caras,

If I flipped a coin 100 times but then

senón que son un oportunista

e vós uns idiotas por deixarmo facer. (Risas)

withheld the results from you from half of those tosses,

Pero é exactamente isto o que toleramos cegamente

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

na medicina baseada en probas.

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

That would mean that I was a chancer

Para min, isto é mala conduta na investigación.

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

But this is exactly what we blindly tolerate

Se eu fixese un estudo e agochase

in the whole of evidence-based medicine.

a metade dos datos dese estudo,

poderiades acusarme con razón de fraude na investigación.

And to me, this is research misconduct.

Aínda así, por algunha razón, se alguén fai dez estudos

If I conducted one study and I withheld

pero só publica os cinco que deron o resultado que quería,

half of the data points from that one study,

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

non o consideramos mala conduta na investigación.

Cando a responsabilidade se difunde

And yet, for some reason, if somebody conducts

entre toda unha rede de investigadores, académicos,

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

patrocinadores do sector e editores de revistas,

we don't consider that to be research misconduct.

por algún motivo atopámolo máis aceptable,

pero o efecto sobre os pacientes é moi negativo.

And when that responsibility is diffused between

a whole network of researchers, academics,

E isto está a suceder agora mesmo, hoxe.

industry sponsors, journal editors, for some reason

Este é un fármaco chamado Tamiflu.

we find it more acceptable,

Os gobernos de todo o mundo gastaron miles de millóns de dólares

but the effect on patients is damning.

And this is happening right now, today.

en acumular este fármaco, e fixérono por pánico,

This is a drug called Tamiflu. Tamiflu is a drug

por crer que reduciría a taxa de complicacións da gripe.

which governments around the world have spent billions

Complicacións aquí é un eufemismo médico para a pneumonía e a morte. (Risas)

and billions of dollars on stockpiling,

and we've stockpiled Tamiflu in panic,

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

E cando os revisores sistemáticos de Cochrane

intentaban reunir os datos

Complications is a medical euphemism for pneumonia

de todos os ensaios sobre se o Tamiflu axudaba nisto ou non,

and death. (Laughter)

acharon que varios destes ensaios quedaran sen publicar.

Now when the Cochrane systematic reviewers

Non podían acceder aos resultados.

Cando comezaron a obter os rexistros deses ensaios por diferentes medios,

were trying to collect together all of the data from all

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

pola Lei pola liberdade da información,

acosando a varias organizacións, o que descubriron era inconsistente.

they found that several of those trials were unpublished.

The results were unavailable to them.

Cando intentaron obter os informes dos estudos,

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

os documentos de 10 000 páxinas

through Freedom of Information Act requests, through

coa mellor interpretación posible da información,

harassing various different organizations, what they found was inconsistent.

dixéronlles que non podían telos.

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

Se queredes ler a correspondencia completa

the 10,000-page long documents that have

e as escusas e explicacións da farmacéutica,

the best possible rendition of the information,

podedes vela na edición desta semana da revista PLOS Medicine.

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

And if you want to read the full correspondence

O máis sorprendente de todo isto, para min,

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

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

é que non só é isto un problema, non só recoñecemos que é un problema,

of PLOS Medicine.

senón que temos que aturar as falsas solucións.

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

Houbo xente que finxiu que este era un problema que xa se solucionara.

Temos os rexistros dos ensaios. Todos dixeron:

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

“Pediremos a todos que rexistren os seus ensaios e publiquen o protocolo,

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

dirán o que van facer antes de facelo

e despois poderemos comprobar se todos os ensaios

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

completados se publicaron.”

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

Pero non se molestaron en usar os rexistros.

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

Entón, o Comité Internacional de Editores de Revistas Médicas

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

dixo: “Xa veredes.

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

Non publicaremos revistas nin ensaios

have been conducted and completed have been published.

salvo que estivesen rexistrados antes de comezar.”

But people didn't bother to use those registers.

Pero non cumpriron.

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

En 2008 houbo un estudo

que demostrou que a metade dos ensaios publicados polas revistas

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

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

de membros do Comité Internacional de Editores de Revistas Médicas

unless they've been registered before they began.

non estaban debidamente rexistrados, e un cuarto deles nin foran rexistrados.

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

Finalmente aprobouse a Lei de modificación da FDA

which showed that half of all of trials published by journals

hai un par de anos, que di que todo aquel

edited by members of the ICMJE

que faga un ensaio ten que publicar os resultados dentro dun ano.

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

Na revista BMJ, na primeira edición de xaneiro de 2012,

And then finally, the FDA Amendment Act was passed

pódese ver un estudo que analiza se esta lei se cumpriu,

a couple of years ago saying that everybody who conducts

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

e resulta que só un de cada cinco o fixo.

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

Isto é un desastre.

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

Non podemos saber os verdadeiros efectos

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

dos medicamentos que receitamos

have done so.

se non temos acceso a toda a información.

This is a disaster.

E non é un problema difícil de resolver.

We cannot know the true effects of the medicines

Temos que obrigar á xente a publicar todos os ensaios realizados en humanos,

that we prescribe if we do not have access

to all of the information.

tamén os máis antigos, porque a lei

And this is not a difficult problem to fix.

só obriga a publicar os ensaios posteriores a 2008,

We need to force people to publish all trials

e non sei que mundo é este no que só practicamos a medicina

baseándonos en ensaios completados nos pasados dous anos.

conducted in humans, including the older trials,

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

Debemos publicar todos os ensaios en humanos,

incluíndo os máis antigos, de todos os fármacos de uso actual,

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

e tedes que dicirlles a todos os que coñecedes

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

que isto é un problema e que non se solucionou.

We need to publish all trials in humans,

Moitas grazas. (Aplausos)

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

(Aplausos)

and you need to tell everyone you know

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

Thank you very much. (Applause)

(Applause)