Chemtrail Awareness
Would you like to react to this message? Create an account in a few clicks or log in to continue.
Chemtrail Awareness

The world will not be destroyed by those who do evil, but by those who watch and do nothing - Albert Einstein
 
HomePortalLatest imagesRegisterLog in
Search
 
 

Display results as :
 
Rechercher Advanced Search
Latest topics
March 2024
SunMonTueWedThuFriSat
     12
3456789
10111213141516
17181920212223
24252627282930
CalendarCalendar
Similar topics

 

 The drugs don't work

Go down 
AuthorMessage
Admin
Admin



Posts : 8049
Join date : 2012-05-29
Location : Manchester UK

The drugs don't work Empty
PostSubject: The drugs don't work   The drugs don't work Icon_minitimeThu 27 Sep 2012, 13:14

The drugs don't work: a modern medical scandal

The doctors prescribing the drugs don't know they don't do what they're meant to. Nor do their patients. The manufacturers know full well, but they're not telling.

Ben Goldacre The Guardian,
Friday 21 September 2012 23.00 BST

The drugs don't work A0158-000112-008


Drugs are tested by their manufacturers, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that exaggerate the benefits. Photograph: Photograph: Getty Images. Digital manipulation: Phil Partridge for GNL Imaging

Reboxetine is a drug I have prescribed. Other drugs
had done nothing for my patient, so we wanted to try something new. I'd read the trial data before I wrote the prescription, and found only well-designed, fair tests, with overwhelmingly positive results. Reboxetine was better than a placebo, and as good as any other
antidepressant in head-to-head comparisons. It's approved for use by the Medicines and Healthcare products Regulatory Agency (the MHRA), which governs all drugs in the UK. Millions of doses are prescribed every year, around the world. Reboxetine was clearly a safe and effective treatment. The patient and I discussed the evidence briefly, and agreed it was the right treatment to try next. I signed a prescription.

Bad Pharma: How drug companies mislead doctors and harm patients

by

Ben GoldacreThe drugs don't work Bad-Pharma-How-drug-companie

But we had both been misled. In October 2010, a group of
researchers was finally able to bring together all the data that had
ever been collected on reboxetine, both from trials that were published
and from those that had never appeared in academic papers. When all this
trial data was put together, it produced a shocking picture. Seven
trials had been conducted comparing reboxetine against a placebo. Only
one, conducted in 254 patients, had a neat, positive result, and that
one was published in an academic journal, for doctors
and researchers to read. But six more trials were conducted, in almost
10 times as many patients. All of them showed that reboxetine was no
better than a dummy sugar pill. None of these trials was published. I
had no idea they existed.
It got worse. The trials comparing
reboxetine against other drugs showed exactly the same picture: three
small studies, 507 patients in total, showed that reboxetine was just as
good as any other drug. They were all published. But 1,657 patients'
worth of data was left unpublished, and this unpublished data showed
that patients on reboxetine did worse than those on other drugs. If all
this wasn't bad enough, there was also the side-effects data. The drug
looked fine in the trials that appeared in the academic literature; but
when we saw the unpublished studies, it turned out that patients were
more likely to have side-effects, more likely to drop out of taking the
drug and more likely to withdraw from the trial because of side-effects,
if they were taking reboxetine rather than one of its competitors.
I
did everything a doctor is supposed to do. I read all the papers, I
critically appraised them, I understood them, I discussed them with the
patient and we made a decision together, based on the evidence. In the
published data, reboxetine was a safe and effective drug. In reality, it
was no better than a sugar pill and, worse, it does more harm than
good. As a doctor, I did something that, on the balance of all the
evidence, harmed my patient, simply because unflattering data was left
unpublished.
Nobody broke any law in that situation, reboxetine is
still on the market and the system that allowed all this to happen is
still in play, for all drugs, in all countries in the world. Negative
data goes missing, for all treatments, in all areas of science. The
regulators and professional bodies we would reasonably expect to stamp
out such practices have failed us. These problems have been protected
from public scrutiny because they're too complex to capture in a
soundbite. This is why they've gone unfixed by politicians, at least to
some extent; but it's also why it takes detail to explain. The people
you should have been able to trust to fix these problems have failed
you, and because you have to understand a problem properly in order to
fix it, there are some things you need to know.
Drugs are tested
by the people who manufacture them, in poorly designed trials, on
hopelessly small numbers of weird, unrepresentative patients, and
analysed using techniques that are flawed by design, in such a way that
they exaggerate the benefits of treatments. Unsurprisingly, these trials
tend to produce results that favour the manufacturer. When trials throw
up results that companies don't like, they are perfectly entitled to
hide them from doctors and patients, so we only ever see a distorted
picture of any drug's true effects. Regulators see most of the trial
data, but only from early on in a drug's life, and even then they don't
give this data to doctors or patients, or even to other parts of
government. This distorted evidence is then communicated and applied in a
distorted fashion.
In their 40 years of practice after leaving
medical school, doctors hear about what works ad hoc, from sales reps,
colleagues and journals. But those colleagues can be in the pay of drug
companies – often undisclosed – and the journals are, too. And so are
the patient groups. And finally, academic papers, which everyone thinks
of as objective, are often covertly planned and written by people who
work directly for the companies, without disclosure. Sometimes whole
academic journals are owned outright by one drug company. Aside from all
this, for several of the most important and enduring problems in
medicine, we have no idea what the best treatment is, because it's not
in anyone's financial interest to conduct any trials at all.
Now, on to the details.
In
2010, researchers from Harvard and Toronto found all the trials looking
at five major classes of drug – antidepressants, ulcer drugs and so on –
then measured two key features: were they positive, and were they
funded by industry? They found more than 500 trials in total: 85% of the
industry-funded studies were positive, but only 50% of the
government-funded trials were. In 2007, researchers looked at every
published trial that set out to explore the benefits of a statin. These
cholesterol-lowering drugs reduce your risk of having a heart attack and
are prescribed in very large quantities. This study found 192 trials in
total, either comparing one statin against another, or comparing a
statin against a different kind of treatment. They found that
industry-funded trials were 20 times more likely to give results
favouring the test drug.
These are frightening results, but they
come from individual studies. So let's consider systematic reviews into
this area. In 2003, two were published. They took all the studies ever
published that looked at whether industry funding is associated with
pro-industry results, and both found that industry-funded trials were,
overall, about four times more likely to report positive results. A
further review in 2007 looked at the new studies in the intervening four
years: it found 20 more pieces of work, and all but two showed that
industry-sponsored trials were more likely to report flattering results.
It
turns out that this pattern persists even when you move away from
published academic papers and look instead at trial reports from
academic conferences. James Fries and Eswar Krishnan, at the Stanford
University School of Medicine in California, studied all the research
abstracts presented at the 2001 American College of Rheumatology
meetings which reported any kind of trial and acknowledged industry
sponsorship, in order to find out what proportion had results that
favoured the sponsor's drug.
In general, the results section of an
academic paper is extensive: the raw numbers are given for each
outcome, and for each possible causal factor, but not just as raw
figures. The "ranges" are given, subgroups are explored, statistical
tests conducted, and each detail is described in table form, and in
shorter narrative form in the text. This lengthy process is usually
spread over several pages. In Fries and Krishnan
(2004), this level of detail was unnecessary. The results section is a
single, simple and – I like to imagine – fairly passive-aggressive
sentence:
"The results from every randomised controlled trial (45 out of 45) favoured the drug of the sponsor."
How
does this happen? How do industry-sponsored trials almost always manage
to get a positive result? Sometimes trials are flawed by design. You
can compare your new drug with something you know to be rubbish – an
existing drug at an inadequate dose, perhaps, or a placebo sugar pill
that does almost nothing. You can choose your patients very carefully,
so they are more likely to get better on your treatment. You can peek at
the results halfway through, and stop your trial early if they look
good. But after all these methodological quirks comes one very simple
insult to the integrity of the data. Sometimes, drug companies conduct
lots of trials, and when they see that the results are unflattering,
they simply fail to publish them.
Because researchers are free to
bury any result they please, patients are exposed to harm on
a staggering scale throughout the whole of medicine. Doctors can have no
idea about the true effects of the treatments they give. Does this drug
really work best, or have I simply been deprived of half the data? No
one can tell. Is this expensive drug worth the money, or has the data
simply been massaged? No one can tell. Will this drug kill patients? Is
there any evidence that it's dangerous? No one can tell. This is a
bizarre situation to arise in medicine, a discipline in which everything
is supposed to be based on evidence.
And this data is withheld from everyone in medicine, from top to bottom. Nice, for example, is the National Institute for Health and Clinical Excellence,
created by the British government to conduct careful, unbiased
summaries of all the evidence on new treatments. It is unable either to
identify or to access data on a drug's effectiveness that's been
withheld by researchers or companies: Nice has no more legal right to
that data than you or I do, even though it is making decisions about
effectiveness, and cost-effectiveness, on behalf of the NHS, for
millions of people.
In any sensible world, when researchers are
conducting trials on a new tablet for a drug company, for example, we'd
expect universal contracts, making it clear that all researchers are
obliged to publish their results, and that industry sponsors – which
have a huge interest in positive results – must have no control over the
data. But, despite everything we know about industry-funded research
being systematically biased, this does not happen. In fact, the opposite
is true: it is entirely normal for researchers and academics conducting
industry-funded trials to sign contracts subjecting them to gagging
clauses that forbid them to publish, discuss or analyse data from their
trials without the permission of the funder.
This is such a
secretive and shameful situation that even trying to document it in
public can be a fraught business. In 2006, a paper was published in the Journal of the American Medical Association
(Jama), one of the biggest medical journals in the world, describing
how common it was for researchers doing industry-funded trials to have
these kinds of constraints placed on their right to publish the results.
The study was conducted by the Nordic Cochrane Centre
and it looked at all the trials given approval to go ahead in
Copenhagen and Frederiksberg. (If you're wondering why these two cities
were chosen, it was simply a matter of practicality: the researchers
applied elsewhere without success, and were specifically refused access
to data in the UK.) These trials were overwhelmingly sponsored by the
pharmaceutical industry (98%) and the rules governing the management of
the results tell a story that walks the now familiar line between
frightening and absurd.
For 16 of the 44 trials, the sponsoring
company got to see the data as it accumulated, and in a further 16 it
had the right to stop the trial at any time, for any reason. This means
that a company can see if a trial is going against it, and can interfere
as it progresses, distorting the results. Even if the study was allowed
to finish, the data could still be suppressed: there were constraints
on publication rights in 40 of the 44 trials, and in half of them the
contracts specifically stated that the sponsor either owned the data
outright (what about the patients, you might say?), or needed to approve
the final publication, or both. None of these restrictions was
mentioned in any of the published papers.
When the paper
describing this situation was published in Jama, Lif, the Danish
pharmaceutical industry association, responded by announcing, in the
Journal of the Danish Medical Association, that it was "both shaken and
enraged about the criticism, that could not be recognised". It demanded
an investigation of the scientists, though it failed to say by whom or
of what. Lif then wrote to the Danish Committee on Scientific
Dishonesty, accusing the Cochrane researchers of scientific misconduct.
We can't see the letter, but the researchers say the allegations were
extremely serious – they were accused of deliberately distorting the
data – but vague, and without documents or evidence to back them up.
Nonetheless, the investigation went on for a year. Peter Gøtzsche,
director of the Cochrane Centre, told the British Medical Journal that
only Lif's third letter, 10 months into this process, made specific
allegations that could be investigated by the committee. Two months
after that, the charges were dismissed. The Cochrane researchers had
done nothing wrong. But before they were cleared, Lif copied the letters
alleging scientific dishonesty to the hospital where four of them
worked, and to the management organisation running that hospital, and
sent similar letters to the Danish medical association, the ministry of
health, the ministry of science and so on. Gøtzsche and his colleagues
felt "intimidated and harassed" by Lif's behaviour. Lif continued to
insist that the researchers were guilty of misconduct even after the
investigation was completed.
Paroxetine is a commonly used
antidepressant, from the class of drugs known as selective serotonin
reuptake inhibitors or SSRIs. It's also a good example of how companies
have exploited our long-standing permissiveness about missing trials,
and found loopholes in our inadequate regulations on trial disclosure.
To
understand why, we first need to go through a quirk of the licensing
process. Drugs do not simply come on to the market for use in all
medical conditions: for any specific use of any drug, in any specific
disease, you need a separate marketing authorisation. So a drug might be
licensed to treat ovarian cancer, for example, but not breast cancer.
That doesn't mean the drug doesn't work in breast cancer. There might
well be some evidence that it's great for treating that disease, too,
but maybe the company hasn't gone to the trouble and expense of getting a
formal marketing authorisation for that specific use. Doctors can still
go ahead and prescribe it for breast cancer, if they want, because the
drug is available for prescription, it probably works, and there are
boxes of it sitting in pharmacies waiting to go out. In this situation,
the doctor will be prescribing the drug legally, but "off-label".
Now,
it turns out that the use of a drug in children is treated as
a separate marketing authorisation from its use in adults. This makes
sense in many cases, because children can respond to drugs in very
different ways and so research needs to be done in children separately.
But getting a licence for a specific use is an arduous business,
requiring lots of paperwork and some specific studies. Often, this will
be so expensive that companies will not bother to get a licence
specifically to market a drug for use in children, because that market
is usually much smaller.
So it is not unusual for a drug to be
licensed for use in adults but then prescribed for children. Regulators
have recognised that this is a problem, so recently they have started to
offer incentives for companies to conduct more research and formally
seek these licences.
When GlaxoSmithKline applied for a marketing
authorisation in children for paroxetine, an extraordinary situation
came to light, triggering the longest investigation in the history of UK
drugs regulation. Between 1994 and 2002, GSK conducted nine trials of
paroxetine in children. The first two failed to show any benefit, but
the company made no attempt to inform anyone of this by changing the
"drug label" that is sent to all doctors and patients. In fact, after
these trials were completed, an internal company management document
stated: "It would be commercially unacceptable to include a statement
that efficacy had not been demonstrated, as this would undermine the
profile of paroxetine." In the year after this secret internal memo,
32,000 prescriptions were issued to children for paroxetine in the UK
alone: so, while the company knew the drug didn't work in children, it
was in no hurry to tell doctors that, despite knowing that large numbers
of children were taking it. More trials were conducted over the coming
years – nine in total – and none showed that the drug was effective at
treating depression in children.
It gets much worse than that.
These children weren't simply receiving a drug that the company knew to
be ineffective for them; they were also being exposed to side-effects.
This should be self-evident, since any effective treatment will have
some side-effects, and doctors factor this in, alongside the benefits
(which in this case were nonexistent). But nobody knew how bad these
side-effects were, because the company didn't tell doctors, or patients,
or even the regulator about the worrying safety data from its trials.
This was because of a loophole: you have to tell the regulator only
about side-effects reported in studies looking at the specific uses for
which the drug has a marketing authorisation. Because the use of
paroxetine in children was "off-label", GSK had no legal obligation to
tell anyone about what it had found.
People had worried for a long
time that paroxetine might increase the risk of suicide, though that is
quite a difficult side-effect to detect in an antidepressant. In
February 2003, GSK spontaneously sent the MHRA a package of information
on the risk of suicide on paroxetine, containing some analyses done in
2002 from adverse-event data in trials the company had held, going back a
decade. This analysis showed that there was no increased risk of
suicide. But it was misleading: although it was unclear at the time,
data from trials in children had been mixed in with data from trials in
adults, which had vastly greater numbers of participants. As a result,
any sign of increased suicide risk among children on paroxetine had been
completely diluted away.
Later in 2003, GSK had a meeting with
the MHRA to discuss another issue involving paroxetine. At the end of
this meeting, the GSK representatives gave out a briefing document,
explaining that the company was planning to apply later that year for a
specific marketing authorisation to use paroxetine in children. They
mentioned, while handing out the document, that the MHRA might wish to
bear in mind a safety concern the company had noted: an increased risk
of suicide among children with depression who received paroxetine,
compared with those on dummy placebo pills.
This was vitally
important side-effect data, being presented, after an astonishing delay,
casually, through an entirely inappropriate and unofficial channel.
Although the data was given to completely the wrong team, the MHRA staff
present at this meeting had the wit to spot that this was an important
new problem. A flurry of activity followed: analyses were done, and
within one month a letter was sent to all doctors advising them not to
prescribe paroxetine to patients under the age of 18.
How is it
possible that our systems for getting data from companies are so poor,
they can simply withhold vitally important information showing that a
drug is not only ineffective, but actively dangerous? Because the
regulations contain ridiculous loopholes, and it's dismal to see how GSK
cheerfully exploited them: when the investigation was published in
2008, it concluded that what the company had done – withholding
important data about safety and effectiveness that doctors and patients
clearly needed to see – was plainly unethical, and put children around
the world at risk; but our laws are so weak that GSK could not be
charged with any crime.
After this episode, the MHRA and EU
changed some of their regulations, though not adequately. They created
an obligation for companies to hand over safety data for uses of a drug
outside its marketing authorisation; but ridiculously, for example,
trials conducted outside the EU were still exempt. Some of the trials
GSK conducted were published in part, but that is obviously not enough:
we already know that if we see only a biased sample of the data, we are
misled. But we also need all the data for the more simple reason that we
need lots of data: safety signals are often weak, subtle and difficult
to detect. In the case of paroxetine, the dangers became apparent only
when the adverse events from all of the trials were pooled and analysed
together.
That leads us to the second obvious flaw in the current
system: the results of these trials are given in secret to the
regulator, which then sits and quietly makes a decision. This is the
opposite of science, which is reliable only because everyone shows their
working, explains how they know that something is effective or safe,
shares their methods and results, and allows others to decide if they
agree with the way in which the data was processed and analysed. Yet for
the safety and efficacy of drugs, we allow it to happen behind closed
doors, because drug companies have decided that they want to share their
trial results discretely with the regulators. So the most important job
in evidence-based medicine is carried out alone and in secret. And
regulators are not infallible, as we shall see.
Rosiglitazone was
first marketed in 1999. In that first year, Dr John Buse from the
University of North Carolina discussed an increased risk of heart
problems at a pair of academic meetings. The drug's manufacturer, GSK,
made direct contact in an attempt to silence him, then moved on to his
head of department. Buse felt pressured to sign various legal documents.
To cut a long story short, after wading through documents for several
months, in 2007 the US Senate committee on finance released a report
describing the treatment of Buse as "intimidation".
But we are more concerned with the safety and efficacy data. In 2003 the Uppsala drug monitoring group
of the World Health Organisation contacted GSK about an unusually large
number of spontaneous reports associating rosiglitazone with heart
problems. GSK conducted two internal meta-analyses of its own data on
this, in 2005 and 2006. These showed that the risk was real, but
although both GSK and the FDA had these results, neither made any public
statement about them, and they were not published until 2008.
During
this delay, vast numbers of patients were exposed to the drug, but
doctors and patients learned about this serious problem only in 2007,
when cardiologist Professor Steve Nissen and colleagues published a
landmark meta-analysis. This showed a 43% increase in the risk of heart
problems in patients on rosiglitazone. Since people with diabetes are
already at increased risk of heart problems, and the whole point of
treating diabetes is to reduce this risk, that finding was big potatoes.
Nissen's findings were confirmed in later work, and in 2010 the drug
was either taken off the market or restricted, all around the world.
Now,
my argument is not that this drug should have been banned sooner
because, as perverse as it sounds, doctors do often need inferior drugs
for use as a last resort. For example, a patient may develop
idiosyncratic side-effects on the most effective pills and be unable to
take them any longer. Once this has happened, it may be worth trying a
less effective drug if it is at least better than nothing.
The
concern is that these discussions happened with the data locked behind
closed doors, visible only to regulators. In fact, Nissen's analysis
could only be done at all because of a very unusual court judgment. In
2004, when GSK was caught out withholding data showing evidence of
serious side-effects from paroxetine in children, their bad behaviour
resulted in a US court case over allegations of fraud, the settlement of
which, alongside a significant payout, required GSK to commit to
posting clinical trial results on a public website.
Nissen used
the rosiglitazone data, when it became available, and found worrying
signs of harm, which they then published to doctors – something the
regulators had never done, despite having the information years earlier.
If this information had all been freely available from the start,
regulators might have felt a little more anxious about their decisions
but, crucially, doctors and patients could have disagreed with them and
made informed choices. This is why we need wider access to all trial
reports, for all medicines.
Missing data poisons the well for
everybody. If proper trials are never done, if trials with negative
results are withheld, then we simply cannot know the true effects of the
treatments we use. Evidence in medicine is not an abstract academic
preoccupation. When we are fed bad data, we make the wrong decisions,
inflicting unnecessary pain and suffering, and death, on people just
like us.


Source:-
http://www.guardian.co.uk/business/2012/sep/21/drugs-industry-scandal-ben-goldacre
Back to top Go down
 
The drugs don't work
Back to top 
Page 1 of 1
 Similar topics
-
» Have A Little Fun At Work
» Do Vaccines Work?
» Canned Heat - On The Road Again

Permissions in this forum:You cannot reply to topics in this forum
Chemtrail Awareness :: Harmful things for your body-
Jump to: