
New Drug Development: Estimating entry from human clinical trials (2003) [pdf] - gwern
http://www.ftc.gov/be/workpapers/wp262.pdf
======
pinaceae
study from 2003, a little bit has changed since then.

but overall, it shows that using the market as a guiding principle for the
selection of which drugs to develop works. it frees humans from making morally
horrible choices. by being profit driven, drug development is automatically
covering the diseases which have the highest number of patients and highest
economic impact.

the latter is difficult to stomach, but from a purely scientific standpoint,
which overlaps with the market, a western life is indeed worth more than an
african one. simple to prove, kill 3000 westerners and the world goes to war.
kill 3000 ethopians and the world goes meh.

it is impossible to target all diseases at the same time. also, through
healthcare spending the world is signalling in cold, hard terms how much their
health is worth to them. which leads to finite resources and, again, the
horrible choice on what to try to cure. supply and demand, where demand is not
only desire but backed by the economic means and will to spend it, works in
this area.

as for the speed of the approval process - better safe than sorry. the only
way to make it faster would be larger human trials, but who exactly wants
that?

~~~
HarryHirsch
_by being profit driven, drug development is automatically covering the
diseases which have the highest number of patients and highest economic
impact._

Your faith in Mammon, the god of money, is touching, but unwarranted. There is
malaria and schistosomiasis, these two are holding back development of the
African continent; there is also the emerging threat of multidrug-resistant
tuberculosis, yet there is preciously little research done into these because
there is little money to me made. At least for Malaria we have the Gates
Foundation.

Meanwhile, the second most-sold medication in the US is a stomach acid
blocker. If you don't think something is wrong there, I think something is
wrong with you.

~~~
pinaceae
please read my comment again, you're missing my point. humanity is voting,
through their wallets, who should be treated for what. as an individual you
despise it from a moral standpoint, sure, but once you reach the level of
treating billions far stronger and fundamental rules takes over. very similar
to the vaccination debate where an individuals opinion should not be respected
for a larger goal, a vaccinated herd of people.

~~~
HarryHirsch
Please read my comment again. "Humanity ... voting, through their wallets" is
punting for short-term gains and missing the bigger picture.

The economic impact of malaria and bilharziosis is immense. They place a heavy
burden on already overstretched public health systems, they discourage
investment, and patients cannot work or attend school. If these two could be
brought under control, sub-saharan Africa would look entirely different.

Let's note that the Panama Canal could only be built after yellow fever was
under control in the area.

~~~
pinaceae
the economic impact on those african nations is immense. but the economic
impact of those nations is miniscule. that is my point. they do not research,
they do not produce, they do not contribute. not just because of malaria, but
because of history, hundreds, even thousands of years.

diabetes will see even more attention now. why? because of china. china is
economically more important to the world, short, middle and long term than
africa. this is an un-emotional, completely rational statement.

and the panama canal is a great example of the west's interests driving
research in medics. white people started colonies, got sick, wanted cures. HIV
started to become a target for research the moment famous white people got
sick and started dying - and in this context someone like magic johnson is
white, western.

sub-saharan africa will always be a shitty place to live. climate, natural
resources - all work against it. not all locations where humans settle make
sense. bangladesh, etc.

------
gwern
"New Drug Development: Estimating entry from human clinical trials", Adams &
Brantner 2003; excerpts:

"This paper analyses a detailed data set on drugs in human clinical trials
around the world between 1989 and 2002. The data provides information on the
probabilities with which drugs successfully complete the different phases of
the trials and the durations of successful completions. The paper shows that
success rates and durations can vary substantially across observable
characteristics of the drugs, including primary indication, originating
company, route of administration and chemistry. It suggests that analysis of
this type of data can help us to answer questions such as: Do AIDS drugs get
to market faster? Do Biotech drugs have higher probabilities of getting to
market? This paper provides some general statistics for analyzing these
questions...Our basic summary is that approximately 1 in 8 drugs that entered
Phase I are launched on the US market.

Note that according to the FDA, only 1 in 1,000 drugs pass the preclinical
stage and are proposed for testing in humans (FDA, 2002). However, almost half
the R&D expenditures occur in the preclinical stage of development (Levy,
1999) Pharmaprojects contains information on 27,987 new branded drug entities
that have reached the late stage development from 1980 to 2002. For the
purposes of this study, we limited the sample size to the 3,328 drugs that
have entered either Phase I, or Phase II, or Phase III of the human clinical
trials somewhere in the world for the first time since 1989.

On average, it takes just under 8 years for a drug to go from Phase I of human
clinical trials to market launch in the US. The same figures for Phase II and
Phase III drugs are 6.1 and 3.7 years respectively. More specifically, an
average drug spends 1.7 years in Phase I, 2.4 years in Phase II, and 3.7 years
in Phase III before launch. Graph 1 presents a graph showing the estimated
duration for the drugs in the data set by their primary indication. While it
takes just 5.5 years on average for HIV/AIDS drugs to get from Phase I to the
market, it takes drugs for Parkinson’s disease almost twice that long to go
through the same process. Drugs for arthritis also spend more than 9 years,
and asthma drugs spend more than 8 years in clinical trials on average.
HIV/AIDS, anti-hypertension, and leukemia cancer drugs are some drugs that
spend less than 7 years in clinical development. Again, this result is
suggestive, but more sophisticated analysis is necessary to determine whether
more important drugs get to market faster, and why."

~~~
icegreentea
Surely part of the discrepancy in timing is indirectly linked to "importance",
since we typically include "lethality" and similar measures into what we
consider important.

Clearly a good chunk of the time spent in trial is to determine side-effects,
contraindications and the like. Given that more "important" targets are also
likely more "lethal" targets, then their bars for acceptable side-effects are
surely going to be lower. I mean, who really cares if there's a potential for
5% of drug takers go blind, if the increase in survival rate over the current
best option is sufficiently high.

------
berntb
There is a problem at the other end, after the clinical trials, if a problem
is found in use.

There were complaints about memory damage for Lipitor for over a decade,
without public warnings (the warnings came recently, a while after the patents
timed out). If this had been found in the human trials, I doubt it would have
been let through.

I do wonder if the large amount of money from selling the drug (a big
bestseller) had influence on any decision...

Nah, regulatory capture is a myth re the medical industry, they wouldn't sell
out our health, would they?

