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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline

« A Dumb Proposal for the NSF | Main | Costing Just Too Much »

April 29, 2013

Just Work on the Winners

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Posted by Derek

That Lamar Smith proposal I wrote about earlier this morning can be summarized as "Why don't you people just work on the good stuff?" And I thought it might be a good time to link back to a personal experience I had with just that worldview. As you'll see from that story, all they wanted was for us to meet the goals that we put down on our research goals forms. I was told, face to face, that the idea was that this would make us put our efforts into the projects that were most likely to succeed. Who could object to that? Right?

But since we here in the drug industry are so focused on making money, y'know, you'd think that we would have even more incentives to make sure that we're only working on the things that are likely to pay off. And we can't do it. Committees vet proposals, managers look over progress reports, presentations are reviewed and data are sifted, all to that end, because picking the wrong project can sink you good and proper, while picking the right one can keep you going for years to come. But we fail all the time. A good 90% of the projects that make it into the clinic never make it out the other end, and the attrition even before getting into man is fierce indeed. We back the wrong horses for the best reasons available, and sometimes we back the right ones for reasons that end up evaporating along the way. This is the best we can do, the state of the art, and it's not very good at all.

And that's in applied research, with definite targets and endpoints in mind the whole way through. Now picture what it's like in the basic research end of things, which is where a lot of NSF and NIH money is (and should be) going. It is simply not possible to say where a lot of these things are going, and which ones will bear fruit. If you require everyone to sign forms saying that Yes, This Project Has Immediate Economic and National Security Impact, then the best you can hope for is to make everyone lie to you.

Update: a terrific point from the comments section: "(This) argument was often made when firms were reducing costs by shutting down particular pieces of R&D. The general idea was that the firm would stop doing the things that were unlikely to work, and focus more on the things that would work, and hence improve financial returns on R&D. This argument is implausible because successful R&D is wildly profitable. Financial returns are only dragged down by the things that don't work. Therefore, any company that could REALLY distinguish with any precision between winners and losers on a prospective basis should double or triple its R&D investment, and not cut it."

Comments (13) + TrackBacks (0) | Category: Current Events | Who Discovers and Why


COMMENTS

1. exGlaxoid on April 29, 2013 10:28 AM writes...

I while back you mentioned the book, "The Economic Laws of Scientific Research", by Terence Kealey. It is a fascinating book, clearly with a bias towards the private funding of research, but giving good data to support his hypotheses. It would be good reading for all of those interested in the funding of science.

One point that he makes is that applied research (aka, NON-ground breaking work) has a higher payoff economically, that basic research, which he claims also has a good payoff (but just not as high as applied). So if Rep. Smith wants to get the biggest bang for the buck, he should propose to only do research that is NOT groundbreaking, as it more often provides a higher payback to the economy.

But as you say, it is difficult to nearly impossible to predict the end result of ANY research as to if it will provide anything useful or not, and if it will create any new value to society, since the results are not know until it is done. And serendipity still provides much of the best result to those who look for new results.

Permalink to Comment

2. Anonymous on April 29, 2013 10:44 AM writes...

...'think that we would have even more incentives to make sure that we're only working on the things that are likely to pay off.'

Unfortunately, our short term incentives are not linked to getting successful medicines on the market - they are linked to 'moving things forward' and it is this divergence that I would point to as being responsible for >50% of the attrition seen in the industry.

We are a long term business which has to navigate a huge number of unknown unknowns in order to be successful. But we behave like arrogant teenagers expecting daddy to bail us out all the time. I'm hoping we grow up soon but a lot of damage has been done already and I still don't think the short term vs long term war has been won. We often back the wrong horse for the worst reasons - and stake the whole house on it.

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3. Anonymous on April 29, 2013 10:56 AM writes...

Oh, the strange state of our world. The Party that--as of late--so detests science gets to suggest how the great ship of scientific research funding navigates.

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4. DCRogers on April 29, 2013 11:29 AM writes...

@4-@6 said: "...Money Dude had noticed that (very large)% of the publisher's revenue came from the best-sellers, and decided that in the future they would only publish best-sellers."

Uh, isn't this the basis of the recent Pharma focus on only "blockbuster" drugs?

'Only publish the bestsellers' == 'Only develop blockbusters'.

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5. Craigar on April 29, 2013 11:30 AM writes...

Obviously Rep. Smith has never heard of Einstein: "If we knew what we were doing, it wouldn't be called Research".

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6. Nick on April 29, 2013 12:56 PM writes...

I'm not a researcher, but we already have something like this in Canada. I don't know all the details, but for our government grants, Scientists are pretty much required to show that their research has commercial value and speculate on what it could be. They also apparently have guidelines against basic research.
This is of course in addition to all the publication restrictions, and gag orders on many scientists (any subject on climate change, as well as many others).
But now I'm just ranting at the Harper government and our creationist chiropractor science minister again.

Permalink to Comment

7. Nick on April 29, 2013 12:57 PM writes...

I'm not a researcher, but we already have something like this in Canada. I don't know all the details, but for our government grants, Scientists are pretty much required to show that their research has commercial value and speculate on what it could be. They also apparently have guidelines against basic research.
This is of course in addition to all the publication restrictions, and gag orders on many scientists (any subject on climate change, as well as many others).
But now I'm just ranting at the Harper government and our creationist chiropractor science minister again.

Permalink to Comment

8. bio_kruncher on April 29, 2013 1:58 PM writes...

The problem for pharma/biotech is really quite obvious and the solution seems clear. Instead of spending so much time and money doing "REsearch" (from Old French recercher to seek, search AGAIN), maybe we should simply be doing "search" instead.

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9. Anonymous on April 30, 2013 4:38 AM writes...

@8 I'm not entirely sure if your comment is plain sarcasm or your true opinion, but in case of the latter: Better study up on your french, as "rechercher" does not mean "to search again", but rather "to research" of "investigate". And isn't that exactly what we are doing?

While the problem is indeed often clear (a disease or whatever), the underlying problem is often not, which is part of the reason the solution is actually far from clear.

Permalink to Comment

10. Anonymous on April 30, 2013 5:07 AM writes...

@9 even if you understand the underlying problem, the solution is still not necessarily going to be obvious.
Since the sequencing of the human genome we (in the industry) have put fat too much focus on trying to find the underlying problem. What we have found so far is that there are usually a large number of 'causes' that vary from patient to patient and actually we have barely scratched the surface of truly understanding how all this comes together to cause a 'disease'.
At current rates of progress it will take centuries to understand all this - great if your a scientist (so much to do!) - not so good if you need to make a return on your investment in 10-20 years.
Industry should be focusing on finding solutions to mitigate the pathology - this does not require total understanding the root cause(s) of disease. Remember blockbusters work by altering healthy functioning pathways that have a beneficial impact on the disease process. They do not fix the damaged pathways directly.

We have not mined out the 'blockbuster' area by any means - we just forgot where to look.

Permalink to Comment

11. Anonymous on April 30, 2013 6:01 AM writes...

I used to work as an investment analyst covering the drug industry. I often heard a superficially attractive - but fundamentally implausible - argument that drug company executives sometimes made about focusing on more attractive areas of research. The argument was often made when firms were reducing costs by shutting down particular pieces of R&D. The general idea was that the firm would stop doing the things that were unlikely to work, and focus more on the things that would work, and hence improve financial returns on R&D.

This argument is implausible because successful R&D is wildly profitable. Financial returns are only dragged down by the things that don't work. Therefore, any company that could REALLY distinguish with any precision between winners and losers on a prospective basis should double or triple its R&D investment, and not cut it.

Permalink to Comment

12. Doug Steinman on April 30, 2013 10:00 AM writes...

Perhaps somewhere down the road we will understand enough about human physiology and pharmacology to allow us to do pharmaceutical research more intelligently. However, that does not mean that we should sit on our hands and do nothing in the meantime. Pharmaceutical research is hard, it is tedious, it takes a long time and it takes a lot of money to come up with compounds that look promising but may never be dosed in humans. It is, perhaps, possible to say that if targets are chosen based more on science and less on what other companies are doing or what the greatest earnings potential is, the duplication of research efforts would be less of a problem than it is today. However, based on what I have seen of senior management in the pharmaceutical industry, this will never happen.

Permalink to Comment

13. ChristianPFC on May 23, 2013 5:04 AM writes...

That reminds me of the following story:

The emperor said to Mozart: "I like your new piece of music, but I think it's too long, can you shorten it by some notes". Mozart replied: "Yes, just tell me which notes to leave out".

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