
Europe votes for clinical trial transparency - oyvindeh
http://www.alltrials.net/2014/europe-votes-for-clinical-trial-transparency/
======
arethuza
Both "Bad Pharma" and "Bad Science" are _excellent_ books - strongly
recommended:

[http://en.wikipedia.org/wiki/Bad_Pharma](http://en.wikipedia.org/wiki/Bad_Pharma)

[http://en.wikipedia.org/wiki/Bad_Science_%28book%29](http://en.wikipedia.org/wiki/Bad_Science_%28book%29)

I wonder if you can get "I am a Nutritionist!" T-shirts?

[Edit: Thanks for pointing out the T-Shirt pretty much does exist].

~~~
JonnieCache
He sells shirts picturing a rubber ducky with "nutritionist" printed
underneath: [http://badscience2.spreadshirt.co.uk/sophisticated-visual-
ga...](http://badscience2.spreadshirt.co.uk/sophisticated-visual-
gag-A18169393/customize/color/1)

Congrats to ben goldacre and everyone else who worked on this!

------
sveme
Getting all the information from all clinical trials will probably spur some
great data mining efforts, on a much broader scale than what has been done so
far. For example, a former colleague of mine used the correlation of published
drug side effects between different drugs [1] to predict potential alternative
therapeutic targets.

Getting all the data on drug efficacy, availability, correlate it with
chemical structure, combine it with the information on other drugs could
potentially help us a lot in predicting better working future drugs and the
workings of existing drugs.

Also, transparency. No more picking out those trials that worked and
conveniently forgetting about those that did not work.

[1]
[https://www.sciencemag.org/content/321/5886/263.abstract](https://www.sciencemag.org/content/321/5886/263.abstract)

------
srean
As far as I know, US laws require that the _`x`_ number of trials demonstrate
the effectiveness of the drug and failured dont need to be reported. But this
does not make sense to me, and I welcome the European laws. In the US system,
even if I have a coin biased badly against coming up heads, if I toss it
enough number of times I will get _`x`_ heads. The tosses cost money and that
is then used to justify the patent system.

One of the oft repeated justification for the absurd levels of IP protection
and patent extensions that pharma enjoys is the huge cost of trials. But if
huge development costs are the reason for these protections to exist, guess
what, these costs will continue to remain huge. Its just self perpetuating.

﻿Patents are primarily a preemptive measure against a hypothetical scenario.
The hypothesis is that unless market pressures are cordoned off, innovation
will stop. It is a believable hypothesis but not a quantitative one, and this
exactly where we need a quantitative one. How many years exactly does one need
to subvert the market so that a satisfactory level of innovation is maintained
? Nobody knows. In these scenario what we need is a feedback system, and
pretty much the only scalable and fair apparatus that we have for such
feedback on economic affairs is the market.

So rather than subverting the market, market should be explicitly and actively
involved to work out this trade-off. How exactly this is to be done needs to
be worked out.

There could be a futures market on patents on drugs undergoing testing:
competitors can promise to buy the patent to the (drug,usecase) pair at a
particular price (even if its a dud) and if the owner decides not to sell the
owner pay a particular compensation. Such measures will spread the risk. There
should be mechanisms for a company to raise money for testing in lieu of
rights over the product.

The initial period of validity of a patent should be short, like 3~6 years,
following which the patent is on the market. Entities can bid to bring the
patent to public domain. The owner(s) bids to retain it. Whoever wins gets the
balance. Of course the "bring it to public domain" bidders will bid less
because profitability is less when its in the public domain, but market
decides who gets to own it. If the owner(s) think they can still extract lots
of profit from the drug, bid high. We should stop handing out blank checks
without a feedback loop, that is just bad design.

~~~
Alex3917
In the US you need two trials showing that a drug is effective, but you can
have an unlimited number showing that it's not effective. Also it doesn't need
to be shown to be effective against a disease, it can just be effective at
reducing some number that correlates with a disease. And you don't need to
show that it's effective in the longterm, only for up to 6 weeks - it could
make the disease dramatically worse in the longterm, and that's fine even if
the drug is meant for longterm use.

There are some rules trying to get all new trials registered, but the rules
aren't followed at all and the FDA doesn't enforce them.

~~~
refurb
Wow, there is a long that is incorrect in your comment.

1\. You are right that typically you need two registrational trials for
approval and yes you can have many trials that show it doesn't work.

2\. You are incorrect that you don't need to show it works against a disease.
_Sometimes_ you can show that you are impacting a biomarker (which I assume is
what you mean by "some number"), but there must be evidence that changing the
biomarker impacts the disease. Without that evidence you will not get
approval.

3\. You are incorrect you only need to show its effective for up to six weeks.
If that were true, why would drug companies be running multi-year trials for
cholesterol drugs? You typically need to show its effective for however long
the drug is taken, but a follow-up period is also required.

~~~
Alex3917
2) C.f. statins. There are any number of books that talk about this. Overdosed
America comes to mind, but you'd be hard pressed to find any recent book about
the pharma industry that doesn't talk about statins.

3) C.f. SSRIs, and Robert Whitaker's book anatomy of an epidemic.

~~~
refurb
2) You are correct that new drugs can be approved by showing a lowering of LDL
(biomarker), but that's only because _the link between LDL lowering and
cardiac risk reduction has already been demonstrated._

The best example I can give you right now are the drugs in development to
treat Duchenne's muscular dystrophy. These drugs work by increasing the levels
of a biomarker called dystrophin. The FDA recently came back and said "nope,
not enough evidence that increasing dystrophin will improve patient's
conditions, therefore we will not approve your drug".

As for the length of depression trials, it has been established that 6-week
trials provide enough evidence to support an improvement in patients. [1]

 _Therefore, a 12-week trial is not necessary for all older patients; rather,
the degree of improvement in the first 4 to 6 weeks identifies patients who
are highly likely to benefit from continuing antidepressant treatment as well
as those who very probably should have their treatment regimen altered at that
point._

However, the depression drugs also run trials for long-term use: "Cymbalta is
indicated for the treatment of major depressive disorder (MDD). The efficacy
of Cymbalta was established in four short-term and one maintenance trial in
adults [see Clinical Studies (14.1)]."

[1][http://www.ncbi.nlm.nih.gov/pubmed/16027559](http://www.ncbi.nlm.nih.gov/pubmed/16027559)

------
ekianjo
> • Require that a summary understandable to a lay person of what was found in
> the trial is published on the register.

Good luck with that. Explaining complex cellular mechanisms to a lay person
without any scientific nor statistical background is a very difficult task.
When you consider modern medicine, you need basic knowledge in genetics,
biochemistry, biology, proteins, drug formulation, pharmacology,
pharmadynamics, toxicity, clinical studies design, to have a proper
understanding of what a study means. We're not talking about aspirin class of
medicines anymore, and more and more drugs are now in the class of _large
molecules_.

~~~
bildung
>> • Require that a summary understandable to a lay person of what was found
in the trial is published on the register.

>Good luck with that. Explaining complex cellular mechanisms to a lay person
without any scientific nor statistical background is a very difficult task.

I don't think that the cellular mechanisms, or generally speaking the mode of
action, are what has to be explained understandable to a lay person. What has
to be explained is the _result_ of the trial.

~~~
ekianjo
Nowadays drugs work in tandem with biomarkers, so how do you explain what a
EGFR mutant individual mean to a layman who has no knowledge about genetics
and mutations ? You'll end up with "Drug A works better than B for EGFR wild
type mutations but no different for other subsets". And? Is the layman
supposed to understand what it means like that?

~~~
bildung
> Nowadays drugs work in tandem with biomarkers, so how do you explain what a
> EGFR mutant individual mean to a layman who has no knowledge about genetics
> and mutations ? You'll end up with "Drug A works better than B for EGFR wild
> type mutations but no different for other subsets". And? Is the layman
> supposed to understand what it means like that?

Of course the layman is not supposed to understand that, that is no
explanation in layman's terms. You can make these sentences understandable by
generalizing it: "We already knew before that the effect of these types of
drugs is very specific to the specific genetics of a patient. Now in this
trial we tried to find out what specific drug works for what specific genetic
combination. The result is that Drug A works better than B for a combination
that is called XY: Whether or not that applies to you can be found out by
<test method>."

~~~
ekianjo
I see what you are aiming at, but the conclusion of clinical trials is almost
never that simple. Drug A works better than B is a matter of statistical
significance, of patient selection (history, previous treatments, genetics),
and you can still register, nowadays, drugs versus placebo as comparators. So
the issue of comparing two drugs together remain where no clinical trial to
compare them in parallel exists. So you'll end up in these situations with :
"Drug A works better than Placebo on X population" and "Drug B works better
than Placebo on Y population", and the poor layman will be left on his own to
understand how the X population is different from the Y one, and what to make
of the results when it comes to comparing A and B.

In other words, it won't help laymen in the end.

At one point, if you really want to understand the clinical trial results, you
need to go in details, and laymen won't be able to do that. So I'm not sure
what they are trying to accomplish here.

Plus, you don't need that laymen language in the first place. Isn't that the
job of journalists who cover scientific discoveries ? I'm afraid we hit
another hurdle here, with the deplorable state of clinical trials results
reporting in the general public by the media. That says a lot about what you
can expect from laymen in terms of scientific comprehension.

~~~
bildung
> I see what you are aiming at, but the conclusion of clinical trials is
> almost never that simple.

Yes, that's the problem with study subjects as complex as humans :) My
academic background is in educational science and things are even fuzzier
there: there never is a simple treatment->result relation because the persons
receiving treatment reflect on that treatment, they are an active part in it.

> In other words, it won't help laymen in the end.

I think I know what you're meaning, but that's the point where I disagree: In
my opinion this is no either/or situation but rather a question of relative
amount of insight that can be given to laymen: Currently they will usually
understand 0% of the scientific abstract. If we assume that a laymen's version
of that abstract loses 80% of the information but is 100% understandable, that
would still be a win.

> Plus, you don't need that laymen language in the first place. Isn't that the
> job of journalists who cover scientific discoveries ?

Absolutely, as journalists are already used to do exactly that. In practice
the result will probably be exactly that: the institution will have science
journalists who will produce these laymen's abstracts.

------
fit2rule
This is _great_ news - no more pharmaceutical profit projects getting pushed
to the forefront, only to discover a few years later that the adverse affects
were buried in 'company proprietary confidental' reports .. makes it safer to
live in Europe!

~~~
refurb
The EMA should work on discovering the drugs that already have publically
reported serious side effects. It took the EMA how long to pull Mediator?

~~~
fit2rule
Corruption also happens in Europe, friend! Big steps, one step at a time.

------
andrewla
In the US, this is already present, to some extent, with FDAAA 801 [1], which
requires that all clinical trials be registered before they start. Missing
things like required publication and the "human-readable" digest, but the
absence of data can be factored in by the FDA when considering approval --
that is, studies that terminate without reaching a finding can be considered
weak indicators of problems, and in the long run, potentially point to
organizations or individuals who might be suppressing negative results.

Even required publication is no cure for this; a result saying "we
inadvertently broke the blind" or "the protocol was poorly implemented" is
perfectly possible even in good faith.

[1] [http://www.clinicaltrials.gov/ct2/manage-
recs/fdaaa](http://www.clinicaltrials.gov/ct2/manage-recs/fdaaa)

------
switch007
For God's sake, _another_ article that conflates Europe and the EU! Lazy, lazy
journalism.

------
barking
Another popular decision by our MEPS just in advance of the EU parliament
elections this summer.

Next comes mom and then apple pie.

~~~
pjc50
The EP is actually quite good at producing the right decisions, especially
when the public remember that it exists and lobby them over this issue.
Unfortunately it's the weakest of the legislating institutions
(Parliament/Commission/Council).

~~~
mercurial
Yes. I'd like to have EU institutions which look more like "normal" democratic
systems, and greater power for the EU parliament. But it's still a lot better
since the Lisbon treaty.

