----- Original Message ----- From: "Deborah Harrell" <[EMAIL PROTECTED]> To: "Killer Bs Discussion" <[email protected]> Sent: Monday, September 12, 2005 9:35 PM Subject: Re: Sources of Drug Innovation > > But _discovering_ that drug can be in the course of > basic or esoteric research, or even seredipitously.
It can be, The existance of this type of discovery is not in dispute. The prevelance is what I consider important. For example, if 5% of drugs are discovered in nature and 5% are discovered duing basic research, with 90% discovered by various drug companies, then the effects of proposed policies would be quite different from a situation where drug discovery was distributed 1/3, 1/3, 1/3%. I appreciate the work you went to finding your example, but that example doesn't address this question. Indeed, I'd guess that if, say, 20% of the drugs came from searches of naturally existing compounds, then the vauge wording in the report would be replaced by more precise wording. > 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: This may be a good point to raise my second point. I'm not sure what you mean by discovering...and I'm starting to think that this is very much at the core of how we see things differently. The nature of experimental research varies with the maturity of a scientific field. For example, high energy physics, for a long time, was a matter of cranking up the energy another factor of 2 or 5 or 10 and looking at the intereractions. Charm was found this way: there was a narrow resonence that was found by two groups once the energies at the accelerators were high enough. Careful work is also needed, of course, and a bit of luck selecting the area in which to run your experiment. But, for this type of work, the connotations of the word "discovery" works fairly well. In the middle of the 20th century, I think this word worked fairly well with medicine too. It was the age of "medical miricles." A few pills could beat diseases that had been plauging humanity for millenia. My mom is very much a product of that time: she expects doctors to provide pills to fix her every ill and has a hard time accepting that not eating properly and drinking enough fluid is the cause of most of her ills. Simply by looking with a bit of care, numerous drugs were found. As a field matures, the "low hanging fruit" is fairly well picked over, and a new regiem begins. New features are not really discovered in the same sense as they were in the infancy of the field. Now, development is much more guided. (BTW, I realize that I'm traveling far afield from the origional question, but I hope that you can see that I'm trying to address a fundamental question that underlies our perceptions: how does the process of research and development work?) At this point, the drop-off in the productivity in simple careful looking is significant. Now, detailed investigation is required. The possibile candidates for detailed investigation are typically infinite (well at least infinite in terms of practical considerations). What is already known is used to rank potential candidates for investigation. It appears to me that you lump this work into "development." This limits "discovery" to a small part of scientific research. Most of what is called "research" is guided detailed investigation. It isn't simple development because there are too many unknowns for that. Indeed, this type of investigation usually requires a very well trained intuition....because of the mix of uncertainy and knowledge. If that is what your catagories mean, then you do include most of what others call research into "development." If not, then I think it is fair to say that drug companies have most of the discoveries of new drugs. Let me comment on numbers a bit below. >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. The obvious question I want to ask is "what is the denomenator?" How many new drugs do we have in for oncology in the last 30 years? If this number is a score or two, then these reports show a significant fraction of drugs are created this way. If this number is in the hundreds, then this report is consistant with other information that I've been given. > This program is an excellent example of how global > cooperation can succeed in the discovery and > development of new anticancer agents. It appears that the claim in this report is that the process they are describing has _some_ meaningful contribution to fighting cancer with drugs. I have no problem with that. > 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... This indicates that Japan has done something > >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. I hope you understand why I don't think the percentage of drugs that come from various sources is a function can be adressed by citing specific examples. > 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." OK, but the word "development" has a very specific meaning in Research and Development. Development usually indicates that there is very little that's really new involved. For example, one colleague of mine at a former company, a man with a great track record of innovations, complained that we no longer did research and development; we only did development. That's part of a trend that I've seen in industry. Drug companies have a far higher research budget than most industries. The oil industry, for example, has gone from having a number of fairly impressive research facilities to having virtually none...during the time I've worked in it. In a highly competitive climate, with minimal profit margins, research is seen as a luxury. It doesn't really pay to do it. >But I will not call 'me-too' > drugs that have no significant advantage over > predecessors "significant discoveries" either. No, those aren't; I agree. One problem that I see is that the climate is shifting away from doing industry research into drugs, because the risks are starting to outweigh the potential rewards. Gautam's point that a company would be a fool to work on a new AIDs drug is a case in point. I know of a start-up that had a lot of venture capital tied up in a single promising new AIDs drug. They were able to get the capital because of the big potential payday. Now, the potential payday must be balanced against the bad publicity a company receives from making large margins on drugs needed by dying people. So far, they've addressed this by mostly getting these margins in the US; accepting smaller margins in Europe and Canada. If the potential for a big payday is lost, then it is reasonable to assume that venture capitalists will lose most of their interest in startup drug companies. One could argue that there is a tremendous amount of inefficiency in this; that the money going to take folks to Pebble Beach and the bonuses paid to salesmen, and the profits going to shareholders is not money spent on research or production. That's absolutely true. Drug companies are the fattest companies I know of. They were shocked at the thought of a 4% layoff when it looked like some sort of price control on drugs were forthcoming. Having suffered through multiple 50% and >50% layoffs, I think of a 4% layoff as barely touching the deadwood. But, the other point is that more efficient companies with smaller profit margins do (with a few exceptions) little or no research. It's all development...and that is done on a minimalist basis. Instead of having a department, one hires a consultant part time for a few years or even a few months to do the job. This is extremely efficient, but it cuts out virtually all research. Universities do fundamental research, as do government labs. But, this is usually not very directed towards a practical goal. For most scientists, the real sexy research is unknown territory....high energy physics was that when I obtained my Phd. Less sexy is fundamental research in more developed fields. Useful results are the least sexy of all. In many ways, scientists need to have their arms twisted to do work that seems mundane to them. Inventing useful drugs is not fundamental....it's really not as sexy as knowing more about how things fundamentally work. The question I think we have to face is what we will do if drug companies stop doing research. This would be their most logical course of action if US prices on patented drugs are cut to, say, Canadian levels. Creating "me too" drugs would, I think, still be profitable, but we might very well face an overwhelming drop in true innovation at drug companies. Given that likely outcome, we need to ask how expensive and how efficient it would be to have governments take up the slack. One way to answer this is to look at the number of truly new drugs that have come out under government patents over the last 20 years vs. the number that have come out under private patents. Dan M. _______________________________________________ http://www.mccmedia.com/mailman/listinfo/brin-l
