
The Deadly Corruption of Clinical Trials - kumarski
http://www.motherjones.com/environment/2010/09/dan-markingson-drug-trial-astrazeneca
======
wpietri
You know, I am a big fan of capitalism. Having started 5 companies, I'd have
to be.

But MBA-style capitalism is a technology for producing short-term wins and
substantial profits next quarter. If you also care about long-term wins or
negative externalities, it's an insufficient technology to apply on its own.

And of course, we hackers know that. Jeff Bezos has been telling the
quarterly-profits people to go fuck themselves for 15 years. And he has been
right to do so. AWS, Amazon Prime, the Kindle, and now their local delivery
stuff: all impossible to achieve if you're more interested in beating
quarterly profit predictions than reshaping the world.

Health care is another area where it doesn't work so well. Consider, for
example, these graphs:
[http://www.washingtonpost.com/blogs/wonkblog/wp/2013/03/26/2...](http://www.washingtonpost.com/blogs/wonkblog/wp/2013/03/26/21-graphs-
that-show-americas-health-care-prices-are-ludicrous/)

I should note that allowing pharma companies to advertise to the public is a
relatively recent change. 1997, I think. And the US is one of only two
countries that allow it. We could change it back.

~~~
protomyth
Its not really the advertising that is a problem. That is the symptom of the
short time frame most drugs need to pay for themselves. Quite a lot of them
only have 3 - 5 years to make the money back.

So, either we figure out a way to make drugs cost less or we extend the
timeframe for profit. Killing the advertising just means the number sold will
be less and much higher for those buying it.

~~~
richardlblair
"Its not really the advertising that is a problem. "

Read this book: [http://www.amazon.com/Selling-Sickness-Pharmaceutical-
Compan...](http://www.amazon.com/Selling-Sickness-Pharmaceutical-Companies-
Patients/dp/156025856X)

It is an advertising problem. Big pharma makes massive profits, so you can't
cite profits as a source of justification for advertising drugs to people who
don't need them. Maybe you should have taken 30 seconds to google GSK's
profits last year, or AstraZeneca who had a bad year last year but still make
2 BILLION dollars.

It goes beyond selling drugs to people who don't need them though, they over
exaggerate and create new attractive names for illnesses. "Social Anxiety",
for example, is not a thing. It's actually called "Social Phobia". A research
study showed that marketing "Social Anxiety" yielded a more positive result,
so big pharma called it just that. I'll leave you to figure out how much big
pharma made off of that little stunt.

~~~
refurb
Two billion dollars on how much revenue? What are their capital investments?
You have to remember pharma has laid off over 100,000 employees in the last
few years due to a lack of new products.

I know a lot of people don't like drug advertizing, but you do realize that it
gets a lot of people to their doctors talking about their health right? And
it's not like a patient can prescribe a drug for themselves, its the doctor
who ultimately decides which treatment to pursue.

~~~
richardlblair
"And it's not like a patient can prescribe a drug for themselves, its the
doctor who ultimately decides which treatment to pursue."

Clearly you don't know very many people in the health field. If a patient
comes in asking for a specific medication, most doctors will just prescribe
that medication assuming the person is suffering from the illness required for
the medication. Where do they get the information for making a diagnosis?
Don't worry, Big Pharma will host an info session or hand out pamphlets so
that doctors know what to look for...

It may be a conversation, but it's the wrong one. Big pharma is notorious for
increasing the potential number of patients for an illness by putting out
advertisements that widen the net for the given illness. Social Anxiety is
great example here, as is ADD. 5% of children in the US are diagnosed with
ADD, only 0.5% are diagnosed with ADD in france. The issue of ADD specifically
goes beyond just advertisements; it speaks to the fact that drug reps have a
real impact on the treatment options doctors present. In France if a child is
having a tough time concentrating in school the find the root of the problem,
in the US they throw meds at the kid and shove him out the door.

The marketing strategies of big pharma are nothing but pure evil. Get people
on more meds, to make more money next quarter.

~~~
refurb
If a doctor is prescribing a medication because the patient asked for it, the
doctor isn't doing their job.

I was talking to an oncologist the other day and he thought the patient
education/advertising was great. Patients who would put off coming to him,
make an appointment because a drug company made them aware that their symptoms
may be a sign of a more serious disease.

Also, he has patients coming to him saying "Hey, I just heard about this new
cancer drug, is it the right one for me?" He thinks the more you can get
patients involved in their own health, the better.

Are there doctors who are too lazy to push back on a patient that demands a
prescription? Of course. Look at how many patients with viral diseases get
antibiotics. Are you going to blame the pharma companies for that as well?

~~~
wpietri
Depends on how you define the job of the doctor.

In a for-profit context, is the job of the doctor to maximize revenues? Or
long-term patient health? In a customer service context, the customer is
always right, after all.

And that's not even counting the doctors who get paid to manipulate other
doctors and their prescription habits.

I am perfectly happy to blame pharma companies for the "everything should be
solved with a pill" notion. After all, that's what the advertising tells both
patients and doctors. One of the major goals of advertising is demand
generation.

I will also blame consumers for falling for it, of course. And for having the
weaknesses of character that advertising exploits. But I'm more willing to
forgive the consumers, in that pharmaceutical companies are professional
manipulators, while the consumers are amateur defenders against manipulation.

------
nodata
Ben Goldacre has been pushing to fix this.

See his campaign site: <http://www.alltrials.net/>

His blog/news site: <http://www.badscience.net/>

His Ted talk:
[http://www.ted.com/talks/ben_goldacre_what_doctors_don_t_kno...](http://www.ted.com/talks/ben_goldacre_what_doctors_don_t_know_about_the_drugs_they_prescribe.html)

~~~
refurb
I highly suggest reading some of the critical reviews of Goldacre's work. He
gets a lot of things wrong and some of his ideas just simple won't work with
the current system.

He's writing a book about an industry that everyone loves to hate. Few people
question a book when it agrees with their preconceived views.

~~~
DanBC
Could you recommend some of the critical reviews?

I've seen some critical reviews that are just nonsense. I don't want to spend
time wading through nonsense, but I realise that maybe he's made mistakes, so
I'd welcome curated suggestions.

~~~
refurb
[http://www.forbes.com/sites/johnlamattina/2013/02/14/bad-
pha...](http://www.forbes.com/sites/johnlamattina/2013/02/14/bad-pharma-maybe-
but-goldacres-selective-use-of-data-is-wrong/)

This is a good critique of only one aspect of Goldacre's book, but it's a good
one.

However, since was written by a former pharma exec, I'm sure people will
dismiss it without reading it.

~~~
wpietri
Is it a good one?

I read the article and the various replies from Goldacre and the author,
including Goldacre's post of the passage in question. I find Goldacre far more
persuasive.

LaMattina claims that Goldacre is cherry-picking data, and gives his
presumably best example. But this example isn't "data"; it's Goldacre
explaining the conclusions of a govenmental report about an incident where 6
experimental subjects nearly died. In writing about science for the general
public, you need to give examples. This seems like a fine example for people
to understand why a culture that promotes publishing everything could save
lives.

------
tokenadult
"September/October 2010 Issue"

The case reported in the Mother Jones article happened at my alma mater, a
state university with many biomedical research studies going on at any given
time. The article author later published a follow-up piece

[http://www.thehastingscenter.org/Bioethicsforum/Post.aspx?id...](http://www.thehastingscenter.org/Bioethicsforum/Post.aspx?id=5147&blogid=140)

in another publication. Two articles by different authors in local
publications last year

[http://blogs.citypages.com/blotter/2012/11/dan_markingsons_s...](http://blogs.citypages.com/blotter/2012/11/dan_markingsons_suicide_jean_kenney.php)

and just last month

[http://www.minnpost.com/second-
opinion/2013/03/controversy-o...](http://www.minnpost.com/second-
opinion/2013/03/controversy-over-u-m-clinical-trial-has-heated-again)

provide further updates about this particular local case.

A group blog post about medical research from 6 January 2012, "Why Do We
Really Need Clinical Trials?"

[http://www.sciencebasedmedicine.org/index.php/why-do-we-
real...](http://www.sciencebasedmedicine.org/index.php/why-do-we-really-need-
clinical-trials/)

examines some of the trade-offs involved in the still flawed, but still
necessary, process of conducting clinical trials of proposed new treatments.
Human beings who propose new treatments often have a bias to suppose that the
new treaments are more safe and more effective than previous treatments--
especially if they have a financial interest in the new treatment. People who
have a financial interest in other treatments, or in not seeking effective
treatment at all (e.g., faith healers) may have a bias that runs in the other
direction. The way to check the safety and effectiveness of a treatment is to
run an honest clinical trial with adequate justification from known science
and sufficient statistical power. But keeping the trial honest involves human
beings disciplining themselves not to jump to conclusions. As Richard Feynman
said to graduates of Caltech: "The first principle is that you must not fool
yourself--and you are the easiest person to fool."

------
lemming
For anyone interested in the generally fucked up state of clinical drug
trials, I highly recommend Ben Goldacre's excellent book Bad Pharma. It'll
make you angry.

~~~
Create
Bad Science also does the job.

The Emperor of All Maladies gives a candid and almost frank overview on how
clinical drug trials are performed "from the inside".

Aspirin the Story of a Wonder Drug is also a nice account of "drug
development" in practice.

------
xijuan
This article has left me speechless.. It reminds me of what my stats prof said
about this kind of research..Researchers doing this kind of research have to
believe that they will find the results the pharmaceutical company wants
before they conduct the study. In other words, they are not testing if the
drug works; they are just showing that the drug works.

~~~
refurb
Most of these clinical trials are triple-blinded. The doctor, patient and
person analyzing the data don't know who took the drug and who took a placebo.

How do they bias the results in that case?

~~~
DanBC
Not all studies are effectively blinded, nor effectively randomised.

Merck-funded researchers trivialised the problems of Vioxx. Those researchers
were not evil or stupid. Subtle influences are hard to spot in yourself.

When you look at the data there's a remarkable gap between independently
funded studies and company funded studies. It's very clear that studies funded
by companies more often show benefits and less often show harm. (There are
several published studies on this.)

And even if the blinding and randomising is effective there's no requirement
to publish. Thus, a company can run ten trials and only publish the one that's
positive.

------
tel
Note that this is already required by law for FDA regulated drugs and devices:
<http://clinicaltrials.gov>

~~~
capnrefsmmat
These requirements are most often ignored. The law requires that trials be
registered and their results published within a year of completion, but most
registered trials never have published results:

<http://www.bmj.com/content/344/bmj.d7373>

The results are simply buried if they're not sufficiently favorable. There
have been a number of meta-analyses which dig up unpublished results (which is
very difficult) and demonstrate that medications no longer have statistically
significant effects when you include the unpublished data. For example:

<http://www.bmj.com/content/341/bmj.c4737>

(Both these papers are open access, so you can read them if you'd like.)

~~~
tel
Cool, thanks for that research. I'm very interested in this problem today.

------
mschuster91
This makes me feel so sad.

I think the biggest lesson to learn from this case is that there has to be a
independent entity in double-blind studies which knows the relation between
test subject and the substance and has the power to interrupt or terminate a
study when people's lifes are at risk.

Again, another fine example of how capitalism does not take unforeseen issues
into account - to refuse to drop out Dan of the study program is "manslaughter
by neglicence" for me (not by malice, as the responsible actors could not have
definite knowledge that Dan would kill himself).

~~~
protomyth
You site capitalism, when all rules governing a clinical trial are strictly
enforced by the FDA which is a government entity. The FDA has study rules and
the entity conducting the study is not the drug company. It is an independent
entity (for example <http://clinicaltrials.mayo.edu>) paid by the drug company
under the supervision of the FDA (in the US).

~~~
logjam
That is some really utterly fascinating spin right there.

Next up: criminals are not really responsible for crime, since "government
entities" like municipal police forces supposedly "strictly enforce" criminal
conduct.

I'm going to take a wild guess here and assume you've never had anything
whatsoever to do with a clinical trial, because the modern FDA has almost
_nothing_ to do with the way a clinical trial is conducted.

A pharma company (the _capitalists_ ) writes the protocol the way they want,
and hires a university/researcher to run the study. They file a simple _two
page form_ with the FDA to apply for an "indication" to study a treatment. The
university/researcher gets the university IRB to sign off on the study
protocol. Sometimes, if the IRB is any good at all, they'll tweak the protocol
to try to protect the research subjects. But guess who picks the IRB members?
The university/researcher making money off the _capitalist_ pharma company.
Guess how that influences an IRB.

The FDA has no input. There is no _supervision_ in any meaningful sense by the
FDA. The _capitalists_ \- researcher and sponsor - run every aspect of the
study. Each decision is theirs.

The decisions spelled out in the article were made by the _capitalists_ \- the
pharma company and researchers.

Barring some complete misstep like all the active arm study patients suddenly
dropping dead, the FDA will eventually (read: years after the study is
completed) examine the data (typically highly massaged by the _capitalists_ )
from the study to make a determination on whether to approve a medication for
sale.

But pretending that the FDA (especially after years of being stripped of
regulatory powers by, you guessed it, _capitalists_ who buy and sell
legislators) has much of anything to do with the way a clinical trial is
conducted is complete bullshit.

~~~
refurb
Wow, that is a very inaccurate description of how clinical trials are run.

How do you explain the clinical holds the FDA puts on clinical studies? The
FDA does monitor clinical studies and stops the bad ones. The often stop them
_before a trial is over_.

I'm guessing you minimal experience with how clinical trials are run. Most
drug companies walk on egg shells around the FDA since they know how much
power their yield.

------
richardjordan
Regulatory capture. Used to be a term we used to criticize corrupt developing
countries. Nowadays it appears to be at the root of so many problems facing
America.

~~~
cynicalkane
What are you talking about? Regulatory capture assumes a working rule of law,
and describes a process by which people subject to the rules of the game try
to rewrite them. In corrupt developing countries the power owns the rules
outright, and regulatory capture is no longer a process. I guess you could
call it "trivial regulatory capture" but it won't get you any Nobel Prizes.
The theory was developed by Chicago School economists who liked to criticize
big government.

Regulatory capture has always been a bug of advanced, sufficiently honest
societies. This is important because it tells us that well-intentioned rule of
law is insufficient for running a democracy if you're not paying attention. I
don't think anyone at the FDA wakes up and says, "I think I'll spend today
getting in the way of good medical care and helping big pharma make money."

~~~
mschuster91
The problem is the privatization of critical infrastructure, a cancer
spreading all over the world.

To quote the last sentence of the article: " _Many academic physicians are
required by their universities to generate a substantial portion of their
salaries by obtaining research grants._ "

Healthcare, basic transportation, energy and water distribution as well as
basic telecommunication infrastructure _must_ be in the hands of the state.
The free market has massively failed in each of these areas, everywhere in the
world. Just look at the US electricity grid, the Berlin water privatization
disaster (less service, more expensive), the US (and partially, German too)
broadband Internet service, the Berlin S-Bahn problems, the (recently HN
frontpaged) problems in the US healthcare system...

Why can't we learn from the countless mistakes made all over the world?!

~~~
refurb
I think we have learned from the mistake made all around the world,
particularly the ones where government run organizations lose billions of
dollars through their shoddy operation of industries.

