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What amuses, annoys, concerns or otherwise interests me – Noodlemaz

ALL the trials!

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Be aware of this new and incredibly important campaign: alltrials.

It’s time all clinical trial results are reported. Patients, researchers, doctors and regulators everywhere in the world will benefit from publication of clinical trial results.

Please sign the petition

Please do. Doctors cannot prescribe the most suitable treatments, if they don’t know what the most suitable treatments are due to lacking information. Patients therefore suffer. Academics cannot plan their research effectively without knowing previous results. The government cannot make appropriate funding decisions without this information, either.

So, help to make ALL clinical trial data available to everyone who needs it – all of us.

Edit 05/02/13: GSK have just signed up! Amazing! Ben has written a quick post on it and here’s the alltrials news.

Here’s a bit about why alltrials is important, in the form of a write-up of Dr Ben Goldacre‘s talk in late 2012 for Soho Skeptics (albeit in a King’s lecture theatre near Waterloo…).

Bad Pharma

Obviously the title of Ben’s new book, which I’m sure he will be happy for you to buy!

So the main problems are: withheld trials; poorly designed trials and ignoring opportunities to run them; the failure to distribute results.

Evidence-based medicine (EBM) incorporates: fair tests; good analysis; spreading information. So, as it stands, a lot of non-evidence-based medicine seems to be going on, and not just from the usual quacks.

Drug development is a tricky business, and an extraordinarily expensive one. But sometimes a new drug gets through the early stages of testing to the point where we need to see what happens when it’s given to people. A famous example of how not to do this is now the trial at Northwick Park hospital (very near where I live now, incidentally) back in 2006.

Groups of patients are not given doses of experimental drugs in quick succession precisely for this reason. If the first has a severe reaction, quickly, you avoid causing it again! Apparently, several years before this a similar molecule was tested, but was abandoned. However, because the information wasn’t published, the warning was hidden. Although immunologists may find universal T-cell activation to be an… unwise pursuit regardless.

The European Medicines Agency (EMA) should have a registry of all European trials, but there are still several thousand missing. 14,000 phase 1 trials are hidden.

In the 80s, anti-arrhythmia drugs were prescribed for irregular heart rhythms following heart attack to prevent deaths. However, 130,000 people died before people noticed it was having the opposite effect.

The Cochrane Collaboration, with its “dead baby forest plotlogo (I think you had to be there, it was funny at the time), was established in the 1980s to comprehensively check results using databases of publications. This allows for systematic reviews and meta-analyses, and, forest plots! From these we can draw a conclusion based on all the evidence available on whether a treatment is effective, has no benefit, or is actively harmful. That allows us to make the best decisions, that is, based on all the information and not what might be a misleading subset of it.

Studies were also withheld regarding Edronax/reboxetine having no benefit or being worse than other available antidepressants. The German version of NICE (IQWiG) made Pfizer show all the data so that doctors could stop potentially harming patients by prescribing it. As a class of drug whose efficacy is constantly debated, a class I have tried myself (briefly and unsuccessfully) and a class many of my friends use, examples like these are particularly distressing.

The existing model that includes poorly designed trials also leads to the development of new, expensive drugs when older, cheap drugs work fine. Too many trials use the “last observation carried forward” method of recording data. So there’s the following scenario:

– people stop taking the drug as they found a lack of benefit or worse, intolerable side-effects

– in carrying forward their last observation of, say, level of pain – the benefit of the drug is massively overstated in the result.

It’s estimated that 50% of all trials are never published..! This can be described as research fraud, or at least misconduct. It is immoral and unethical. Yet no one seems to talk about it, none of the Royal Colleges have officially spoken out. Surely these kinds of groups should be spearheading this campaign?

What about the regulators? Well, they don’t get all the information either. They also have to make different kinds of decisions from doctors and patients. They still need all the data.

We need substandard treatment options. Some people cannot tolerate the gold standard, so they need alternatives. Regulators sometimes see black and white works/doesn’t work situations, and that’s not generally the case in medicine.

Now, the EMA rather than the MHRA approves UK medicines. Cochrane asked EMA for information on two weight loss drugs (Orlistat and one other) but they refused to provide it for 3 and a half years. They argued that it was “confidential information”, such as in the trial design (it wasn’t), that there was an administration burden involved (there wasn’t); patients were exploited for commercial gain. The EMA is now releasing more, but not enough.

£500m was spent on Tamiflu. £5 out of every £20 in the NHS’ drug budget. Roche are still holding some of the information on around half of the trials; they promised to produce it in December 2009 but we are still waiting for it.

GSK are similarly despicable and have had to cough up a $3bn fine (not a huge percentage of their profits, of course).

Apparently the abpi behave in a surprisingly similar way to homeopaths when they are criticised.

“Conflicts of interest are situations, not behaviours – judge people by their actions” – Ben

Is there a concerted campaign to change this? Not really, said Ben at the time – now there is! Patient groups need to write to Pharma companies. There’s a lack of leadership and poor reporting on the issue; MPs are ill-advised.

No one makes the challenge so people continue to deny the problem, because they can?


What can we do?

[Apart from signing the petition!] Doctors need to write to the Royal College(s)/BMA to complain about publication biases etc. – send any replies received over to Ben [and the campaign]. Patient groups should contact the relevant drug companies. Anyone can!

What about non-UK companies? … if a company is attacked on home ground, won’t they move?

Asked senior politicians about this. The abpi said prescriptions talks with the NHS drove down drug prices. The prospect of job losses is fine. What’s not fine is letting them withhold data “or jobs will go” – patients are harmed by this!

So what levers are there? NICE; they could not approve drugs until all data has been shared.

Can we at least get Europe to do this? Coalition pressure, Australia, New Zealand, Japan… The government can lobby colleagues coherently. No marketing without total results. Unknown results – how many deaths? New policies? Better decisions?

What’s a good response to alt-med fans and peddlers accusing of ‘conspiracy’?

It isn’t, it’s the inevitable behaviour of corporations running under incompetent regulatory frameworks. It’s rational. Imperfections – but people are stirring to improve EBM.

Quacks are thousands of times worse.

But if they can be allies, if they could help fix EBM problems..?

Quacks do provide interesting case studies and useful demonstrations of what EBM is because what they do is not.

Pharma companies do not respond to placebo, so we need to do something real. Antivax and quacks have poisoned the well here.

NB/ RandomiseMe should be up around April/May 2013. Random tests (not necessarily medical) to take part in.

PatientsLikeMe is useful for logging symptoms, side-effects etc.

Why isn’t the financial sector more concerned?

Generally it’s not a company value issue because consequences are miniscule (Tamiflu is still selling).

GSK fine didn’t affect their stocks, about 10% of their revenue?

Jan 2012 report showed 1/5 trials are put on clinicaltrials.gov, but no fines given.

Thus ends my patchy notes – finally, sign and share the petition!


Author: noodlemaz

I prefer to think of myself as a realist rather than a pessimist, but perhaps that's just optimistic. Honest, atheist, scientist, feminist.

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