Some snippage for brevity, and longish quotes b/c I
think you can't get to Medscape articles unless you're
registered-  (and this is a minimal reply b/c it's
getting late, but there are lots of articles to scan).

> Dan Minette <[EMAIL PROTECTED]> wrote:
> > From: "Deborah Harrell" <[EMAIL PROTECTED]>
> > > Dan Minette wrote:
> > > > > >From: "Deborah Harrell"

> > > > > > You are not taking into account the
> advances made by universities and publicly-funded
> institutes.
> > > > > > For-profit drug companies *are not* the
> only or even primary sources of drug innovation.

> > > > > So, if we looked, we'd see that most of the
> > > > > drug patents are held by
> > > > > governments and universities?  Or are you
> > talking about something different
> > > > > when you speak of innovation.

> > > > Correct:  drug _development_ is without
> question the purview of the pharmas ..<snip>..Drug
> _discovery_
> > > > comes from multiple sources, sometimes quite
> > > > accidentally <snip>

> > >...<snippage>said that only about 5% of drugs are
> > > developed from
> > > non-traditional sources, such as herbs or the
> > > example you gave.
> > > Fundamental research has been and is being done
> at universities and government facilities... <snip>

> > Which is what I said *originally* - check that
> first sentence above again.
 
> I saw your first sentence, and it is inconsistant
> with what I've been told
> by people who work in the field.  Development of a
> drug only comes _after_
> it shows promise in animal tests. 

But _discovering_ that drug can be in the course of
basic or esoteric research, or even seredipitously. 
Naturally-occuring chemical compounds were a large
source of many 'new' drugs in past decades (think
antibiotics esp.), and in oncology is still very
important:

http://www.medscape.com/viewarticle/433928
Anticancer Drug Development: A Global Perspective
[Disclosures:'no significant financial disclosures'
for the 3 authors listed]
Michelle L. Washart, PharmD

At the international symposium "Anticancer Drug
Discovery and Development Throughout the World," held
during the 38th Annual Meeting of the American Society
of Clinical Oncology,[1] leaders from around the globe
led thought-provoking discussions on issues of drug
development.

Identifying New Products: A Collaborative Effort
The session opened with Dr. Gordon Cragg from the
Developmental Therapeutics Program at the National
Cancer Institute (NCI) providing a review of the NCI's
Natural Product Repository Program. This program is
becoming increasingly important in the treatment of
cancer, as a number of important anticancer agents
have been derived from natural products, including
plant-derived agents (such as the vinca alkaloids,
taxanes, and topoisomerase I inhibitors),
microbe-derived agents (such as the anthracyclines,
epothilones, and rapamycin analogues), and
marine-derived agents (such as bryostatin and
dolastatin 10). 
Dr. Cragg described the NCI's process for establishing
collaborations with source countries to develop
programs to screen potential anticancer agents.
Currently, such collaborations exist with over 15
countries, including Australia, Brazil, China, Costa
Rica, Fiji, New Zealand, and Pakistan.

There are 2 methods by which this process occurs. A
"Letter of Collection" agreement is used in arranging
to allow collecting of materials from a foreign
country for screening, evaluation, and testing. This
agreement contains terms related to conservation,
training, technology transfer, and the protection of
rights of the source country.

By contrast, a "Memorandum of Understanding" is used
when the foreign country provides extracts and
compounds directly to the NCI. In this agreement, NCI
collaborates with a qualified source country
organization (SCO): the SCO collects the materials and
NCI assists in screening the compounds for anticancer
or anti-HIV activity. By covering developmental costs,
NCI also collaborates with the SCO in developing new
agents that meet established criteria. 

This program is an excellent example of how global
cooperation can succeed in the discovery and
development of new anticancer agents.

Re: government discovery and development:
...In 1998, the Cancer Therapeutics Research Group was
formed as a collaboration between the University of
Singapore and Australian groups. Since that time, Hong
Kong and US sites have joined the group. There were 3
primary concepts behind the collaboration: (1) to
provide a platform for drug development simultaneously
in Asian and white populations; (2) to provide the
pharmaceutical industry with an Asian-Pacific database
for drug development; and (3) to study cancers that
are common to Asians such as stomach cancer. Dr. Wong
described 2 interesting trials initiated by this
group. The first was a combination trial with
docetaxel and carboplatin in non-small-cell lung
cancer (NSCLC) that demonstrated a 65% response rate
in Asian patients and only a 31% response rate in
whites. This difference was evaluated and determined
to be due to differences in the metabolism of
docetaxel. Specifically, since Asians metabolize
docetaxel much more slowly than do whites, they
demonstrated an AUC that was almost double that of the
white patients. The data from this trial are expected
to be published shortly.

The second study Dr. Wong described was presented at
Saturday's poster session.[2] This study demonstrated
interethnic differences in myelotoxicity with
doxorubicin and cyclophosphamide in breast cancer
patients. Of interest, a substantially higher portion
of Singaporean patients (55%) experienced severe
myelotoxicity vs Australian patients (20%).  Dr. Wong
ended his presentation by stating that the future of
this field of research is in microarray technology and
developing gene expression profiles -- a concept
echoed in many talks throughout this conference.

Offering the Japanese perspective, Dr. Nagahiro Saijo
from the National Cancer Center Hospital in Japan
described the current state of anticancer research in
Japan. Over the past few years, research has greatly
improved largely because of the creation of the
Japanese Clinical Oncology Group (JCOG) by the
government. Dr Saijo also discussed Japan's
contribution to cancer drug development including the
contribution in the development of irinotecan, ZD1839,
tegafur, and other agents...

>From a pharma:
...The final address of the session was delivered by
Dr. David Parkinson, from Novartis Pharmaceuticals,
who discussed global drug development from the
perspective of a global pharmaceutical company. Dr.
Parkinson noted that although the opportunities are
enormous, there are significant challenges to global
drug development. Some of the more major threats
facing the pharmaceutical industry include the
increase in the cost of research and development
without an attendant improvement in productivity (ie,
the number of agents approved) the longer development
time without a corresponding decrease in development
risk; and the increasingly conservative regulatory
climate coupled with the increasingly difficult
reimbursement setting.
The current reality in industry-sponsored clinical
trials is that the majority of registration trials are
focused on the United States and Europe. The changing
reality, however, is that as the number of new agents
increases, there is an increased need for patients in
clinical studies that cannot be met within the United
States. Thus, the interest in drug development
globally is increasing within the pharmaceutical
industry, particularly because there is an increased
capability of countries outside of the United States
to perform these trials.

Some of the factors to consider in the move to truly
global trials are: How common is the disease in
various parts of the world? Is there a uniformly
accepted standard treatment? Are there likely to be
differences in the magnitude of response or in the
toxicities within certain populations?

> That development takes years, IIRC 5
> years is a goal now for fast tracked drugs, but it
> represents only a
> fraction of what drug companies do in R&D.  Unlike
> most companies now, drug companies actually do R.
> 
> They need to find the candidates in the first
> place....few candidates are
> handed to them by universities or are found by
> happenstance. They have to
> search for candidates.  This search is done by trial
> and error sometimes,
> and it is now guided by computer programs that take
> knowledge of chemical
> reactions and models likely results of various
> chemical combinations.  It
> is much more research than what I do, for example.
> It is actual trailblazing research.

The article I cited deals with cancer research/drugs
only; I will look for others, frex antibiotics and
antihypertensives, heart drugs etc.
 
> Part of it is semantics, I guess.  But, in the world
> of R&D, development has a very specific meaning.  
 
>  The first compensated neutron tool was a real
> research project.  By your
> standards, since quantum mechanics is known, it's
> just a development
> project, but I think that doesn't acknowledge what
> it takes to innovate.
> Let me try one more example.  By your standards,
> only Maxwell could be
> credited for finding E&M.  Everything else (radio,
> radar, TV, generators) was just development.

That's a teeny bit of exaggeration...   ;)
I already acknowledgeded the pharmas near-undisputed
in the drug development arena, and no-where did I call
it "just" or "merely."  But I will not call 'me-too'
drugs that have no significant advantage over 
predecessors "significant discoveries" either.

Debbi



                
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