
Nearly 1 in 3 drugs have a significant safety issue after FDA approval - ohaikbai
http://www.latimes.com/science/sciencenow/la-sci-sn-fda-drugs-safety-20170509-story.html
======
tvural
Negative press like this probably contributes to the FDA being so
conservative. They get none of the benefits when a great new drug is approved,
but get scapegoated when they approve something dangerous even to small
numbers of people. So they just approve as few drugs and medical devices as
they can get away with - it's a massive misalignment of incentives.

One might think drugs would be more dangerous if the FDA were less
conservative, but I suspect the opposite. If it takes you ten years and 2
billion dollars to release a new drug, and then you find out it has some
terrible side effect in 0.1% of the population, you don't get to fix the
problem. You might not withdraw it either, since the drug would still be a net
good for society. And if one drug is approved instead of ten, patients are
forced to stick to the flawed solution.

The far bigger problem than drugs with side effects is a lack of drugs. Around
1/3 as many drugs get approved today relative to 1970, and the costs of a drug
approval have risen 5 times faster than inflation since then. Medicine has
been an anti-technological field for the last few decades - it's doing less
with more. The most valuable biomedical companies are the ones that have been
around since the 1800s - one could imagine what computers would look like
today if IBM were still the largest IT company.

~~~
warent
"The far bigger problem than drugs with side effects is a lack of drugs."

I'm not so sure about that. Arguably the market is actually oversaturated with
drugs, and too many people rely on them to an absurd extent rather than
changing behaviors and habits to improve overall health.

~~~
jamescostian
> too many people rely on [drugs] to an absurd extent rather than changing
> behaviors and habits

It's not that simple. If I go to school and someone gets me sick, you wouldn't
"this is your fault, you shouldn't have such bad habits like going to school."
Furthermore, what are these good behaviors and habits? I can find a million
articles on the internet telling me that cold showers are a good habit and
another million saying hot showers are a good habit - which one is objectively
right?

Yes, there are people who decide to use drugs instead of making simple changes
(e.g. my friend who drank a large bottle of Jack in a day and needed to get
his stomach pumped - he should have just vented to a friend about his girl
issues). But there are so many other people out there who don't fit that
description, and there isn't any true scottsman with objectively perfect
behaviors and habits. So I don't think it's unreasonable to help people out
with more options for drugs that may be better for some people than what we
already have.

~~~
Mikushi
> can find a million articles on the internet telling me that cold showers are
> a good habit and another million saying hot showers are a good habit - which
> one is objectively right?

The one that works for you? We are all different, depending on ethnicity,
medical history, and a million other factor your diet, life style and life
choices will affect your health differently.

~~~
jamescostian
How do you define "works for you"? For example, say I take cold showers and
decide "this makes me cold; I don't like it" and then start taking hot showers
everyday. But then imagine that one day, we find a link between hot showers
and cancer.

How was I supposed to know that cold showers would have been better for me?
Should my "bad habit" really be blamed?

------
refurb
As someone who works in the industry, this shouldn't be much of a surprise.
Most drugs have a very low incidence of serious side effects. Even over the
counter products do. The reason they are approved is that they are so rare.

A great example of a serious side effect is Toxic epidermal necrolysis (TEN)
and Stevens–Johnson syndrome (SJS). There are many everyday drugs (ibuprofen,
antibiotics, etc) that can cause this rare disorder. Your skin basically
sloughs off and you end in a burn ward. Super rare, but they happen.

~~~
amyjess
Last month, my doctor gave me a shot of toradol (for reasons I don't want to
go into). The allergic reaction I got from that shot had me terrified I was
experiencing the early symptoms of TEN at first.

I had hives all over my body, plus muscle pains all over my arms and legs (at
its worst, I could barely hold a razor and needed a cane in order to shuffle
around). You know what comes up when you search for bumps all over your body
combined with pain? Yeah, TEN.

Fortunately it was just allergy-induced hives and myalgia, and I understand
that the pain I went through functioned like an acute case of rheumatoid
arthritis, but that was still nasty. I ended up in the emergency room twice.
The first course of steroids they prescribed me wasn't long enough or strong
enough: the hives never fully went away, and the myalgia came back as soon as
I finished the prednisone. So I had to go back, and then they gave me a shot
of decadron and put me on a two-week course of prednisone.

Yeah, that wasn't pleasant. At all. The side effects I suffered from the
prednisone were awful and insidious, but at least it killed the allergic
reaction.

Oh, and during that time, a friend of mine died, and her death was all over
the local news because of how mysterious it was (they still haven't solved it
or even released a coroner's report yet). April 2017 was terrible all around.

~~~
lostboys67
How much where you on? I have had to take pred (40mg /d) and did not have any
major side effects apart from one incidence of mood swings went from stressed
to giggling inside of 10 min (I told my boss I think I had better go home and
have a lie down).

It did ramp up my appetite "mmm doughnuts" and my aggression a bit.

I do know there are some funkier side effects but I did not get those

------
sfRattan
On the flip side, many drugs approved by governments in the rest of the
Western world languish in the FDA's queue for years. I contracted a common
illness while living in Germany as an exchange student, and was prescribed
medication by a doctor there which I had to fight over with my insurance (then
my parents' family plan) for reimbursement because the drug had not yet been
approved by the FDA. We got the reimbursement eventually, and the price was
eminently reasonable anyway: something like 70-ish Euro. But drug prices in
the United States are another can of worms entirely...

I recall the incident well because the computer the doctor used to enter
information in the late 2000s was a Commodore 64 with that distinctive lighter
band around the display edge.

~~~
da02
What was the illness? Did you ask the doctor why he was using a Commodore 64?

~~~
sfRattan
I deliberately didn't specify the illness for privacy reasons, though it was
an airborne contagious disease. I did not ask him why he was using such an old
machine, but it seemed to work and he was rather old also. The detail only
sticks out because it was so odd.

~~~
da02
It's great everything worked out in the end.

------
noir_lord
A more interesting question would be how many would have a significant safety
issue _without_ FDA approval.

Given the complexity of the drugs, the body and the interaction with other
medication I'm impressed it's only 1 in 3 particulary since as mentioned down
thread only 1.3% get taken off the market (1 in 77).

~~~
orblivion
You would also have to consider whether the drug companies would choose an
alternate route for validating safety. I think they would care at least some
amount about their reputation for safe products.

~~~
cc439
The free market has made this work in the realm of electronics and electrical
devices (UL), as well as the automobile industry (TS16949). The risks posed by
bad products in the healthcare sector are perceived as far more dangerous but
the sheer ubiquity of theoretically dangerous, yet completely trusted products
produced with nothing but private party testing lends credence to the argument
that we wouldn't be worse off without the FDA.

The safety of US made nutraceuticals is also a testament to that fact although
they have become increasingly regulated by the FDA and FTC despite a lack of
prominent examples to back the need for further regulation.

~~~
rayiner
The difference between UL and a automobiles and drugs is that it's obvious if
an electronic product or automobile works. It's very hard to tell if a drug
works--and most don't.

Nutraceuticals are a great example of the problem: they're safe because
they're bogus and don't do anything. But because they're not regulated people
waste tons of money (and suffer because they don't take drugs that do actually
work). The

~~~
omarchowdhury
Saying nutraceuticals don't do anything is quite a claim on your behalf.

------
bhalperin
Scott Alexander [1] has some useful (critical) comments: "significant safety
issue" is not necessarily what it sounds like.

[1]
[https://slatestarscratchpad.tumblr.com/post/160559317596/kit...](https://slatestarscratchpad.tumblr.com/post/160559317596/kitswulf-
currentsinbiology-at-least-those)

~~~
afarrell
It is worth noting that Scott Alexander is an MD who is currently finishing
his residency.

~~~
leekyle
I was recently reading "American Sickness" by Elisabeth Rosenthal. She was
talking about how an anti-nausea medication was taken off the market for
safety issues because it caused heart issues at 50 times the dose usually
taken. After doctors were forced to use Zofran instead, which costs at least
20 times more.

------
dcolgan
In one of my favorite books, Antifragile, Nassim Taleb argues that health is
largely subtractive - if you want to be healthy, remove unnatural things from
your body (sugar, medicines, sitting too much, etc), and only undergo surgery,
go to the hospital, or take medicine in very serious cases where the harm of
not doing something outweighs the potential complications. Especially since
hearing more about more about how the American health system is not exactly
incentivized to always look out for the best interest of the patient, I'm
inclined to agree with him.

~~~
criley2
>if you want to be healthy, remove unnatural things from your body (sugar,
medicines, sitting too much, etc),

?? What is "natural"? How do you define "natural"? Is there a single point in
human evolution that you call "done" and emulating that discrete point is
natural, and anything before or after is 'unnatural'?

I always struggle to understand "natural" woo because it is, at its core, an
undefined and meaningless word with absolutely no scientific or medical
relevance.

>and only undergo surgery, go to the hospital, or take medicine in very
serious cases where the harm of not doing something outweighs the potential
complications.

So, basic modern medicine? If your general doctor is recommending unnecessary
medications or not doing cost/benefit for you, then _medicine_ isn't broken,
your doctor is.

>Especially since hearing more about more about how the American health system
is not exactly incentivized to always look out for the best interest of the
patient, I'm inclined to agree with him.

Why on earth would you conflate the profit motives of healthcare middlemen to
imply that the science behind medicine isn't credible?

This is a shockingly ignorant statement openly peddling ludditeism and
implicitly denouncing science in favor of the pitiful naturalism fallacy.

Really surprised to see such irrationalism on this forum.

~~~
dcolgan
I think some nuance here is needed. My understanding of "natural" primarily
comes from an understanding of evolutionary history. If humans have been doing
something for millions of years, it is likely to be more "natural" and
therefore not cause harm compared to recently invented things. But it is not a
black and white thing, but rather a spectrum.

Some examples: Trans fats were invented because they thought saturated fat,
which was consumed by humans for a long time, were not healthy, and this new
thing was supposed to be better. Then it was found to cause all kinds of
problems and are now banned in many places. Here I think it was pretty cut and
dry.

An anecdote I've found others corroborate: I used to have foot pain. Some
people suggested orthotic insoles, but I also found the barefoot shoe
proponents saying that shoes without any padding at all (more "natural") work
better. Five years later I never have any foot pain. The Vivobarefoot or
Vibram Fivefingers shoes are definitely not something that was around a
million years ago, but the principle is the same.

In healthcare, an example in the book is how many people are prescribed statin
drugs if their cholesterol is too high, even if there is no other visibly
problematic symptoms. Taleb would argue the far better solution is to improve
the person's diet, or just wait and see if something happens, than to start
taking a drug that isn't.

The author once strained his back lifting weights. The doctor suggested an
expensive and invasive surgery. Instead he just rested for a while and the
problem went away. On the other hand, my mom recently had neck surgery to
replace several vertebrae. She'd been in pain for years and nothing could fix
it. So in this case I think Taleb would agree that the risk of a dangerous
surgery might be worth it in that case.

An extreme example from the book: in the early 20th century children were
given doses of radiation to treat acne. We obviously look at this and scoff,
but it is the same idea.

> Why on earth would you conflate the profit motives of healthcare middlemen
> to imply that the science behind medicine isn't credible?

I'm looking at the profit motives to see where I should be cautious. I feel
like this very site is where I've read many articles about how scientific
studies had bias because of funding from the companies invested in a certain
answer. From what I can see, if you follow the money, you can explain a great
deal of the behavior of large institutions.

So I'm not at all advocating ludditeism or against science. Rather I'm against
scientism (I think the word he uses in the book) - the belief that science has
all the answers and that newer things are inherently better than older things
just because they are. They may in fact be better, but not always. Sometimes
atheists I meet are just as close-minded as the religious.

~~~
hnhg
So you're saying, if an anecdote fits your theory, it's proof, and forget
searching too hard for anything that runs contrary to your beliefs?

I think science works a bit better than this, and I put my faith in that.

~~~
dcolgan
A good hypothesis can be used to make predictions. I'm just saying with my
foot issues that the heuristic of "subtractive medicine is better than
additive medicine" was able to predict that removing padding from my shoes
would make my problem go away. And it did. That does not prove anything but it
worked here.

~~~
hnhg
Say that the padding had worked, you might have rationalised it to to be that
it's unnatural to walk on hard surfaces ("our ancestors never walked on
concrete").

There are also probably many instances in your life where this hasn't worked,
but you've cherry picked the example that does.

It's very likely that your body healed itself regardless of the padding. You
might have just needed time. You've figured that it's removing the padding but
it might not be a factor. It's why studies need decent sample sizes to make
strong conclusions.

~~~
dcolgan
That's fair enough, but also why I looked for other people who had similar
experiences. I'm definitely not always right, that is true. I am not a doctor,
lawyer, or accountant.

------
vitorbaptistaa
Not directly related to the OP's story, but can be useful for someone reading
these comments.

We've scraped the Drugs@FDA data as part of OpenTrialsFDA [1], a project aimed
to make it easier to search their documents. It contains data from about
Oct/2016, because they changed their website's layout just after we finished
the scraper (if you'd like to contribute, it shouldn't be difficult to update
the scraper [2]). All the data is available in a Postgres database at
[https://explorer.opentrials.net/data](https://explorer.opentrials.net/data),
or via [https://fda.opentrials.net](https://fda.opentrials.net).

I'm happy to talk with anyone interested in this kind of data via
[https://gitter.im/opentrials/chat](https://gitter.im/opentrials/chat).

[1]:
[https://opentrials.net/opentrialsfda/](https://opentrials.net/opentrialsfda/)
[2]:
[https://github.com/opentrials/opentrials/issues/705](https://github.com/opentrials/opentrials/issues/705)

------
jrapdx3
I fear this is one of those subjects where querying any 5 people will yield 10
opinions, and in the end the issues remain poorly illuminated.

FWIW I've been prescribing medications for a number of decades and pretty well
understand the general benefits and limitations of pharmocotherapy as a
treatment method.

To save you a lot of time and trouble studying this very complex field, let me
boil it down to these few words: _any medication can cause any side-effect at
any time_.

All drugs cause side multiple effects. The ones we like we call "benefits" or
therapeutic effects, those we don't like are "adverse effects" (AEs). Useful
drugs will have few troublesome AEs vs. good benefits, but it's a relative
matter, a judgement call about what's good, bad or ugly.

It partly depends on the condition the drug is used for. In life-threatening
situations we'll accept bad AEs, for example, cancer chemotherapy agents. For
merely annoying, self-limiting problems, like a common cold, we wouldn't take
big risks.

However, no drug is absolutely safe. _All_ are capable of causing serious
problems in at least a few people. Therefore we must use all drugs carefully
and with thorough knowledge of the risk/benefit trade-offs, but there are
never any guarantees of outcomes.

Another aspect is that often severe AEs are quite uncommon. Think of a side-
effect that occurs in 1/100000 recipients. What are the odds this will be
detected in drug registration trials? Most drugs are tested on a perhaps a few
thousand people before approval, and often fewer subjects than that. The
chances of encountering these outcomes is remote until drugs have been around
for years, even decades before the harmful effects can be gleaned.

One drug that became notorious for incidents of fatality in the late 90's was
nefazodone (Serzone), an antidepressant. I was peripherally involved with
research on the matter. Basically what came to light was that in people with
rare (like 1 in a million) mutations in certain liver enzymes, the drug was
metabolized along a pathway that produced compounds causing fatal liver
necrosis. After 18 deaths around the world became known, the association was
made and the drug was withdrawn from the market. There was no way to predict
this would be an effect of the drug when it was approved.

Of course AEs are very seldom fatal. The point here is that AEs (serious or
not) are quirky, inevitable and randomly distributed. The benefits are always
intertwined with finite risks. It's not surprising in the least that a high
proportion of drugs are associated with troublesome AEs (with varying
definitions of "troublesome").

------
solomatov
I think that's ok. Drugs have side effects, and we should balance these side
effects with their benefits.

------
helloweirld
Only three of the events were withdrawals, meaning that only 1.3% of approved
drugs were recalled off the market. Consider that this is a really impressive
error rate. Scientific studies are allowed to be wrong 5% of the time; the FDA
is wrong 1%.

The others were “boxed warnings” and “safety communications”. These are often
pretty minor. I can’t read the full study you linked, so I don’t have their
examples, but some of the most recent FDA boxed warnings are:

Last year, the FDA added a new boxed warning to all opiates and
benzodiazepines (drugs which have been around for the better part of a
century) telling doctors that really, no, seriously, don’t prescribe these
together. People have known not to prescribe them together for the better part
of a century, but the FDA decided they should be louder about it so they added
a new boxed warning. Also, I’ve prescribed opiates and benzodiazepines
together several times when it’s been clinically necessary, and as long as
you’re not an idiot about it it’s fine (but please don’t try mixing opiates
and benzodiazepines at home without your doctor’s permission!).

There’s a boxed warning on Ritalin that it might cause heart problems in kids.
Later research has shown this is probably false, but the FDA worried about it
one time ten years ago and decided to add a boxed warning, which nobody ever
got rid of. Ritalin remains as popular as ever.

In 2006, the FDA added a boxed warning to warfarin, a blood thinner which at
that time had been out 52 years, saying that if you took too much of it, it
could make your blood too thin. This year, the FDA released a safety
communication, discussing a very common antiseptic used by millions of people
yearly, that, over the last fifty years of use, about one person per year has
had a serious allergic reaction to it, and if you have a serious allergic
reaction to it, you should call 911. Maybe another way of making this point is
to list the psychiatric drugs that have gotten boxed warnings sometime after
they were released: every antidepressant, every typical antipsychotic, every
atypical antipsychotic, every benzodiazepine, lithium, Depakote, Lamictal,
etc. You may recognize this as every single psychiatric drug (except BuSpar,
which doesn’t work).

What I’m saying is that an FDA boxed warning isn’t “Oh god, how did this
poison ever make it through the approval process?!”. It’s an incremental
update to existing safety regulations on a generally good drug as more
evidence comes in and people’s priorities shift. The study says on average
these drugs were out for four years before the FDA added the warning. That’s
probably because these are rare side effects that only appear after many
people have been taking the drugs for several years. For example, if one in
every million people who uses antiseptic soap has an allergic reaction, we
can’t very well ban antiseptic soap until we try it on a million different
people. That’s why post-marketing surveillance is a natural and important part
of the regulatory process.

Another example: antipsychotics are not FDA-approved for dementia. I don’t
even know if any company has ever tried to get antipsychotics FDA-approved for
dementia. Giving demented people antipsychotics is a bad idea if there’s any
other option. But people do it anyway, and then the demented people get heart
problems and die. The FDA eventually figured that out and put a boxed warning
on antipsychotics not to give them to demented people if possible. This didn’t
show up before approval because nobody wanted them to be given to demented
people so there was no study about whether it was a good idea.

My point is that boxed warnings are a natural part of pharmacology, that some
new side effects being found post-approval means the system works, and that
the FDA continues to have a 98.7% accuracy in approving drugs that don’t need
to be withdrawn later.

Source:
[https://slatestarscratchpad.tumblr.com/post/160559317596/kit...](https://slatestarscratchpad.tumblr.com/post/160559317596/kitswulf-
currentsinbiology-at-least-those)

~~~
Cozumel
> 'I can’t read the full study you linked, so I don’t have their examples'

Then you go on to cite _tumblr_?!

Just read the actual paper: [http://sci-
hub.cc/10.1001/jama.2017.5150](http://sci-hub.cc/10.1001/jama.2017.5150)

~~~
tgb
That is, at least, the tumblr of a psychiatrist resident who writes a lot on
the subject of FDA regulations. I really recommend his blog posts on the
subject, like this one about how different countries (Russia and US
particularly) use different drugs and for the most part don't even seem to be
so interested in trying the drugs available elsewhere:
[http://slatestarcodex.com/2014/08/16/an-iron-curtain-has-
des...](http://slatestarcodex.com/2014/08/16/an-iron-curtain-has-descended-
upon-psychopharmacology/)

~~~
tgb
In case anyone is still reading this thread, that author now has a post on
this very topic: [http://slatestarcodex.com/2017/05/18/postmarketing-
surveilla...](http://slatestarcodex.com/2017/05/18/postmarketing-surveillance-
is-good-and-normal/)

------
thepompano
I wonder if this will impact Donald Trump's campaign promise to get the FDA to
sign off on all of those drugs awaiting approval.

 _Reforms will also include cutting the red tape at the FDA: there are over
4,000 drugs awaiting approval, and we especially want to speed the approval of
life-saving medications._

[https://assets.donaldjtrump.com/_landings/contract/O-TRU-102...](https://assets.donaldjtrump.com/_landings/contract/O-TRU-102316-Contractv02.pdf)

------
wu-ikkyu
This study conducted in 2003 indicates that iatrogenesis (accidental deaths
caused by conventional medicine) is the leading cause of death in the US.

[http://articles.mercola.com/sites/articles/archive/2003/11/2...](http://articles.mercola.com/sites/articles/archive/2003/11/26/death-
by-medicine-part-one.aspx)

------
Pfhreak
Naively, I feel like the same could be said about appliances, or kitchen
items, or software, or food, or vehicles, or ...

"Significant safety issue" seems both poorly defined, and doesn't address the
rate of incidence or the conditions necessary to create that issue. Many drugs
have safety concerns when not used correctly, for example. Or in small
populations.

------
aantix
It already costs 2.5 billion to bring a medication to market..

[https://www.scientificamerican.com/article/cost-to-
develop-n...](https://www.scientificamerican.com/article/cost-to-develop-new-
pharmaceutical-drug-now-exceeds-2-5b/)

Adding additional quality measures only stands to increase that number.

~~~
mikeyouse
That's a very industry-friendly number with a very industry-friendly
calculation;

> _CSDD’s finding, a bellwether figure in the drug industry, is based on an
> average out-of-pocket cost of $1.4 billion and an estimate of $1.2 billion
> in returns that investors forego on that money during the 10-plus years a
> drug candidate spends in development._

Backing some figures out then, the actual cash cost is $1.4 billion to develop
a drug. They rely on a 11.8% clinical success rate for that figure, so if you
back out the drugs that were abandoned along the way (since they won't need
late-stage human safety studies), it's more like $165M to develop a self-
originated drug if you believe the self-supplied pharma figures.

It's even more suspect when their $2.6 billion headline figure for increased
from $800M in 2003 when the cost of capital has decreased since then and
average approval times have been halved:
[http://www.raps.org/uploadedImages/Site_Setup/Regulatory_Foc...](http://www.raps.org/uploadedImages/Site_Setup/Regulatory_Focus/News/2016/03/subs.png)

~~~
jcranmer
> Backing some figures out then, the actual cash cost is $1.4 billion to
> develop a drug. They rely on a 11.8% clinical success rate for that figure,
> so if you back out the drugs that were abandoned along the way (since they
> won't need late-stage human safety studies), it's more like $165M to develop
> a self-originated drug if you believe the self-supplied pharma figures.

The actual cost to develop a single successful drug, if you pass all the
clinical trials, is in the ballpark of $500M or so. Dividing the total cost by
success rate isn't an accurate number since the cost varies based on where you
fail: the expensive bits are the clinical trials at the end, so finding out
that the drug is a failure sooner cuts your costs considerably. The Phase III
clinical trial by itself is well over $100M, much more if you're doing a
large, long-term clinical study for a difficult problem (say, Alzheimer's or
cancer). Something like 50% of all drugs fail in phase III.

~~~
mikeyouse
> _The actual cost to develop a single successful drug, if you pass all the
> clinical trials, is in the ballpark of $500M or so._

I'd love to see a source for that.. Not even Pharma claims figures that high.
Take Sofosbuvir for example; It was discovered in 2007, was developed through
2011 and then the company was acquired by Gilead while they had multiple Phase
III trials running. In that time period, they spent a total of $230 million on
R&D -- for all of their candidates. They also had two other compounds that
were undergoing Phase II trials.

> _The Phase III clinical trial by itself is well over $100M, much more if you
> 're doing a large, long-term clinical study for a difficult problem (say,
> Alzheimer's or cancer)._

Nah. Not even close. HHS's most recent look placed Phase III at $19.9M, with
very few classes of drugs costing more than $50M total for all phases
(Ignoring IV since those are often more marketing than R&D)[1]:

[https://aspe.hhs.gov/system/files/images-
reports/examination...](https://aspe.hhs.gov/system/files/images-
reports/examination-clinical-trial-costs-and-barriers-drug-
development/Figure%203.png)

> _Something like 50% of all drugs fail in phase III._

The average is closer to 60% success rate, with some areas up to 75%
success.[2] And it's not like if you fail the Phase III, the compound is
scrapped and all of that work is wasted. There's an entire industry behind
drug "repurposing, repositioning and rescue" to purchase and retarget
promising compounds.

[1] Full study: [https://aspe.hhs.gov/report/examination-clinical-trial-
costs...](https://aspe.hhs.gov/report/examination-clinical-trial-costs-and-
barriers-drug-development)

[2]
[https://www.bio.org/sites/default/files/Clinical%20Developme...](https://www.bio.org/sites/default/files/Clinical%20Development%20Success%20Rates%202006-2015%20-%20BIO,%20Biomedtracker,%20Amplion%202016.pdf)

------
bluetwo
Every so many years there is a push by the industry for tort reform. They want
to be legally protected from any damages as long as the FDA has approved the
drug.

Bookmark this article to remind yourself next time they make this push.

~~~
bluetwo
I have wonder why this was down-voted.

------
Qantourisc
You want to introduce drugs/foreign molecule in a body? and hope everybody
will respond perfectly to this ? Better change the body and not the drug ;)

So imo the most important thing for the FDA: 1) Does it actually do what it's
intended to do ? 2) Determine conditions before you can take the drug. Drugs
that have very rare side-effect -> over the counter. Dangerous drugs ->
pretesting/screening of the patient before even considering given the drugs.

------
pasbesoin
(In the U.S.,) It's government funding and research that turns up most novel
drugs (as opposed to tweaking existing formulae and mechanisms).

And, there needs to be government funding (e.g. to an independent academia)
and research that follows and studies the commercial as well as research lives
and implementations of these drugs.

------
grandalf
The idea that we should all simply trust one entity to "approve" drugs is
pretty farfetched.

I think there should be multiple "stamps" of approval from a variety of
entities that consumers can use to determine whether they want a particular
drug...

Why not have stamps from the FDA, insurer groups, physicians groups, etc.

~~~
criley2
It's not farfetched in the least to have one entity approve the drugs based on
roughly $1 billion dollars over 10 years[1] worth of research.

What's more farfetched to me is allowing private, profit-motivated
corporations the unfettered ability to produce this expensive research.

Fortunately the all-but-oppressive regulation of the FDA from GLP and GMP to
insanely rigorous science-based four phase system of testing is IMO the
greatest achievement in science-based regulation in human history.

People simple do not understand or respect the awesome power of the scientific
method being the basis of government regulation.

[1]
[http://onlinelibrary.wiley.com/doi/10.1002/9780470403587.ch1...](http://onlinelibrary.wiley.com/doi/10.1002/9780470403587.ch1/summary)

or go to [https://www.amazon.com/Drugs-Discovery-Approval-Rick-
Ng/dp/0...](https://www.amazon.com/Drugs-Discovery-Approval-Rick-
Ng/dp/047019510X) and use the "look inside" feature to see page 4: "It is
estimated that, on average, a drug takes 10-12 years from initial research to
reach the commercialization stage. The cost of this process is estimated to be
over $1 billion USD" (2005)

Another fun tidbit you'll find in the book: On average, for every 10,000 NME's
that begin research, 1 NME will receive FDA approval. (where NME is a new
molecular entity, a novel new drug).

So you've got a market where you have to begin development on 10,000 products
to get 1 product into the market, on a 10 year runway. Could you imagine that
in tech? 9,999 pivots per product!

~~~
orblivion
I will admit that some of us may be inappropriately dismissive of the
usefulness of regulators. However pointing to how long it takes and how much
money is spent could just as well imply inefficiency as rigor.

You say that we don't need competing regulation agencies because this one is
rigorously scientific. By what mechanism, would you say, does this singular
institution maintain quality?

~~~
criley2
>By what mechanism, would you say, does this singular institution maintain
quality?

Interesting question, quality is such a foundationally important and vital
subject for the FDA. Hard to answer, it's like asking what does Microsoft do
to maintain software quality? The answer has to be long and in depth... And in
this case, the FDA is over 100 years old, born out of atrociously horrendous
food and chemical accidents in America, so this is a century-old organization
founded out of a desire to improve quality in food and drugs (Upton Sinclair's
1906 book The Jungle is considered important reading when understanding the
FDA's mission)

So with the FDA (with CDER, the drug/med device/biologic/etc side of the FDA),
the basic question they ask (and require all this work to prove is): Is your
drug better than existing treatments and placebo treatments?

So, fundamentally, they have an ethos which only grants approval not for
equivalence, but scientifically proven, double blind tested superiority to
existing approvals. This is an ethos that less is more. That only quality
matters. That a business should go bankrupt before 1 bad drug is approved.

But beyond that, to look into the question of quality, that's a great question
that is very important to the core of the FDA's mission.

I would point, in recent decades to the emergence of "phase 4" trials -- post-
release trials.

Now it is not enough to get approved, now we continue to test the efficacy and
safety of the drug after it goes to market, and can and have pulled drugs
(that cost billions in losses for companies) which seem to pass initial 3
phase approval but which, in market, demonstrates a lack of safety or
efficacy, has side effects that change the calculus against existing
treatments, or similar.

Also, another angle of quality is enforcement. What happens if GLP, GMP,
safety, efficacy, is violated? You might be happy to learn that the fines that
the FDA levies are some of the largest fines against businesses in history.
Outside of BP-Gulf and the 2008 mortgage fines, the FDA sweeps the list of
billion-dollar-level fines.

So you have a core commitment to quality at every level. An ethos continued
from founding seeking scientifically provable superior quality at every
judgement. GLP and GMP in the labs and factories which are the most rigorous
site regulation you'll find in America. The 4 phase system of trials,
including post-market data. And the most aggressive corporate enforcement arm
in America, with an impressive list of profit-busting fines that no other
regulator can stand next to.

~~~
orblivion
I appreciate the long response, and I kind of feel bad because I meant my
question in a rather different way. And (assuming you even notice my response
at this point) perhaps I'm going to take us down a road of talking past each
other.

My question is about incentives. An unchallenged organization, I would think,
would have the tendency to perpetuate itself, and sing its own praises, and
deem itself very important.

Let me put it this way: The analogous question isn't what Microsoft does to
maintain quality. The question is, how does the world at large maintain
Microsoft's quality (and efficiency?). A decade or so of security
embarrassments and OSX's and Linux's better reputation got them to step up
their security game. Recently, Apple's design got them to step up their design
game. If you asked a manager for a canceled project inside the company they
might have a great process plan, a great argument for why they need more time
and resources, and a great explanation for why they and their team are
important. But they may have no sense of the needs of the outside world. This
exchange between Steve Jobs and an (apparent) Apple employee highlights this
mentality, vs the mentality of an entrepreneur who does respond to the outside
world: [https://www.youtube.com/watch?v=FF-
tKLISfPE](https://www.youtube.com/watch?v=FF-tKLISfPE)

It very well may be that the FDA does a fantastic job of filtering out bad
stuff. And, as (I may as well come out and say it) a libertarian, perhaps I am
guilty of not appreciating all the work that has gone into setting it up. But
it doesn't mean that they have a sense of the correct amount of rigor to
apply, money to spend on various aspects of their operation, etc. That's why
we like to see competition in the field of certification.

"That a business should go bankrupt before 1 bad drug is approved." and "some
of the largest fines against businesses in history" are great examples of
_perhaps_ being a bit too rigorous or punitive. You can always apply more and
get at least marginally safer drugs. But you may also get fewer drugs through
the process, or more expensive drugs, or companies that decide not to even
bother starting the process (which you'll never hear about), and (maybe) more
people die on net as a result.

I will grant to you, taking your claims at face value, that you make a
convincing case that the FDA at least hasn't gotten _lax_ for the lack of
outside corrective influence. I guess the mechanism for improvement there is
simply human dedication, and I will buy that argument.

------
BurningFrog
These decisions are huge and uncertain tradeoffs between how many will die
from a drug being stopped or delayed and how many will die from it being
approved.

If no drugs ever were recalled or had significant safety issues after
approval, that would be a certain sign the process is erring on the side of
non approval.

------
throwaway91111
I'm a little shocked it's that low. What medication doesn't have significant
safety issues?

~~~
Shinchy
Jewish Penicillin?

~~~
upvotinglurker
Somewhere there must be a few people severely allergic to some ingredient in
chicken soup.

------
jdavis703
The bigger question, is how many drugs in total have safety issues? Would it
be 2/3 drugs if approval was made easier or eliminated? Would it be less?

------
wnevets
And people are pushing for more drugs to be approved with less testing.

------
jmcdiesel
Yet a safe alternative in many cases (not all) is still illegal federally and
in many states... while we continue to allow pharma to roll in money made from
products knows to have horrible side effects...

------
known
safety issues != side effects

------
fiatjaf
End the FDA.

------
aaron695
I'd fucking hope so.

Drugs should do stuff.

They are used to stop bad things, if lesser bad things happen they are still
great. And if greater bad things happen to some people they are also great.

Whats next, study finds chainsaws can cause harm.

