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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

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September 15, 2009

Industrial Research: More Grounded in Reality, or Not?

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Posted by Derek

My post the other day on why-do-it academic research has prompted quite a bit of comment, including this excerpt from an e-mail:

I would also note that mediocrity is hardly limited to academia. I cannot tell you the number of truly dumb things that I continue to see happening in industry, motivated by the need to be doing something - anything - that can be quantified in a report. The idea that industry is where reality takes command is depressingly false, and I would guess that the same thing that distinguishes the best from the rest in academia also applies in the "real world."

Well, my correspondent is unfortunately on target with that one. Industry is supposed to be where reality takes command, but too often it can be where wishful thinking gets funded with investor's cash. I'm coming up on my 20th anniversary of doing industrial drug discovery. I've seen a lot of good ideas and a lot of hard work done to develop them - but I've also seen decisions that were so stupid that they would absolutely frizz your hair. And I'm not talking stupid-in-hindsight, which is a roomy category we all have helped to fill up. No, these were head-in-hands performances while they were going on.

I can't go into great detail on these, as readers will appreciate, but I can extract some recurring themes. From what I've seen the worst decisions tend to come from some of these:

"We can't give up on this project now. Look at all the time and money we've put into it!" This is the sunk-cost fallacy, and it's a powerful temptation. Looking at how hard you've worked on something is, sadly, nearly irrelevant to deciding whether you should go on working on it. The key question is, what's it look like right now, compared to what else you could be doing?

"Look, I know this isn't the best molecule we've ever recommended to the clinic. But it's late in the year, and we need to make our goals." I think that everyone who's been in this business for a few years will recognize this one. It's a confusion of ends. Those numerical targets are set in an attempt to try to keep things moving, and increase the chance of delivering real drugs. That's the goal. But they quickly become ends in themselves, and there's where the trouble starts. People start making the numbers rather than making drugs.

"OK, this series of compounds has its problems. But how can you walk away from single-digit nanomolar activity?" This is another pervasive one. Too many discovery projects see their first job (not unreasonably) as getting a potent compound, and when they find one, it can be hard to get rid of it - even if it has all kinds of other liabilities. It takes a lot of nerve to get up in front of a project review meeting and say "Here's the series that lights up the in vitro assay like nothing else. And we're going to stop working on it, because it's wasting our time".

"Everyone else in the industry is getting on board with this. We've got to act now or be left behind." Sometimes these fears are real, and justified. But it's easy to get spooked in this business. Everyone else can start looking smarter than you are, particularly since you see your own discovery efforts from the inside, and can only see other ones through their presentations and patents. Everyone looks smart and competent after the story has been cleaned up for a paper or a poster. And while you do have to keep checking to make sure that you really are keeping up with the times, odds are that if you're smart enough to realize that you should be doing that, you're in reasonably good shape. The real losers, on the other hand, are convinced that they're doing great.

I'm not sure how many of these problems can be fixed, ours or the ones of academia, because both areas are stocked with humans. But that doesn't mean we can't do better than we're doing, and it certainly doesn't release us from an obligation to try.

Comments (27) + TrackBacks (0) | Category: Academia (vs. Industry) | Drug Development | Who Discovers and Why


COMMENTS

1. Anonymous on September 15, 2009 7:51 AM writes...

Great post, so accurate. I left the industry a while back, and some of the reasons so eloquently communicated above played a part in that decision. The 'sunk-cost fallacy' was utterly crippling at my shop - we had dozens of molecules limping along and we ALL knew they were going nowhere... But no one seemed willing to kill them off. Such a waste of time and money.

Still enjoying the blog Derek, keep it up!

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2. milkshake on September 15, 2009 8:36 AM writes...

when careers are at stake, people will act in their self-interest rather than doing good science. Middle management is about the control of people and projects, about the goals on flowcharts being met on time.

I lived under communism - some diseases of the industry are rather similar (but the money is a lot better). I think the best description of these problems is to be found in Parkinson's laws - see the Injellitis etc

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3. CMCguy on September 15, 2009 9:29 AM writes...

Great Post Derek as indeed industry can seem to trip into these same pitfalls over and over. The "Potency uber all mantra" in medchem can lead to problems and even failure down the road. Unfortunately such dumbness does not end at discovery stage as development can be full of repetitive inane activities, sometimes in the name of Regulatory compliance but typically fueled by pressures to just get things done on a project without thinking how to do better.

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4. Spartic on September 15, 2009 9:51 AM writes...

Get used to the Academics being in charge. There will be no industrial research.

I suppose Lily cutting 14% of its staff isn't even worthy of comment anymore!

http://finance.yahoo.com/news/Lilly-to-cut-14-pct-of-staff-apf-3326749016.html?x=0&.v=13

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5. DylanE on September 15, 2009 9:58 AM writes...

Any stories of the seemed-stupid-at-the-time-but-turned-out-to-be-brilliant-in-hindsight variety?

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6. gyges on September 15, 2009 10:03 AM writes...

"Get used to the Academics being in charge. There will be no industrial research."

Good point made by Spartic, above. In the UK we have the disease of pseudo-industrialists; that is, academics subsidised by Universities who undermine small and medium enterprises. These double salaried enterprises have most probably destroyed a great number of fledgeling companies.

When will it end?

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7. Hap on September 15, 2009 10:35 AM writes...

Isn't comparing the most stupid behavior of both groups the wrong standard? If I am to be judged on my most stupid thoughts, words, and acts, I'm screwed. It seems more reasonable to judge the two (at least for their relative capabilities at drug development) for what they've done (and what resources they've used to do so) rather than just their most stupid moments, and while people in academics have come up with drugs (with significant external help), the rate and effectiveness of drug development in industry seems significantly higher than in academics.

Analysis of the habitual stupidity seems more useful in understanding why the drug industry appears to have been less effective at finding drugs recently than as to whether they do so better than academic drug development groups.

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8. Sili on September 15, 2009 10:41 AM writes...

Meeting the pseudogoals rather than the real goals happens everywhere. It's crippling healthcare and other public services here exactly because administrators like to deal with easily quantifiable numbers.

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9. Yancey Ward on September 15, 2009 11:28 AM writes...

Too funny and sad at the same time. Seen multiple examples of all of these during my career, and, yes, they are "head in the hands" obvious to a lot of us.

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10. MTK on September 15, 2009 12:20 PM writes...

It's not just us down in the trenches. The chasing of non-sensical goals is obvious to everyone, including middle and upper management. Management is bound by shareholders and investors metrics just as we are bound by their metrics. This is a natural outgrowth of any bureaucracy, which is what any organization that has departments is.

BTW, the best one I remember was "We have better compounds than X, but we'll save those to meet next year's objectives, since we've already met this year's with X."

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11. Johnathan on September 15, 2009 12:40 PM writes...

The behaviors you describe are in no way limited to the pharmaceutical industry. I worked for several years at a large, Fortune 50 semiconductor manufacturer and personally witnessed the waste of 10s to 100s of millions of dollars from dysfunctional decision making. There were projects that were head-in-hands obviously wrong, yet accountability was so diffuse it was literally impossible to stop them. When they eventually failed or were cut after enormous investments in time, people, and money, the same groups of people would get assigned to the next disaster :-)

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12. Diversity on September 15, 2009 1:59 PM writes...

Sounds just like some Governemnt research programs I used to keep stumbling across.

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13. TomB on September 15, 2009 2:37 PM writes...

I don't think such decisions are limited to pharma companies. Project/Department leaders in any business have a strong incentive to make it look like the work they are doing is valuable. It is always a challenge to get the right people into leadership positions so that the company makes good business decisions. This is why business people, MBAs, and other types of overhead can add value. You're always going to get some inefficient decisions - the companies that do the best at limiting it tend to do better in the long run.

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14. billswift on September 15, 2009 3:06 PM writes...

Meeting planning numbers rather than real goals is a really extensive problem everywhere. There is an extensive literature on this in software engineering, especially.

As far as the "everybody in the industry" argument, if true that everyone else is concentrating on that, maybe you should be looking elsewhere for a profitable project. The more competition there is in researching something, the more likely someone else is to be first with a salable product, which will leave you totally profitless, or at least dragging with a similar me-too product.

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15. Jordan on September 15, 2009 3:31 PM writes...

"People can count better than they can read."

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16. Hap on September 15, 2009 3:33 PM writes...

It may be optimistic to assume that people can do either.

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17. molecular architect on September 15, 2009 3:41 PM writes...

#13. "This is why business people, MBAs, and other types of overhead can add value."

LOL, these people are the major source of non-sensical goals!

The best thing industry could do to improve matters would be to downsize these folks.

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18. Industrial Chemist on September 15, 2009 5:46 PM writes...

Hap's comment (#7) is a very good one, but I would be curious to make the comparison based on dollars spent (ie investment on return). It wouldn't be quite fair (I don't think) to just compare number of accomplishments (drugs to market, say) of industry and academia. It would seem to me that there should be some sort of normalizing ratio. That is if we're interested in actually comparing the two, rather than tooting our own collective horn.

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19. Bored on September 16, 2009 9:48 AM writes...

Our current manned space program, based on the Space Shuttle and the ISS is a great example of what happens when you just do something for the sake of doing it.

When JFK gave his Rice University speech where he challenged the U.S. to land a man on the moon, he forgot to mention follow-up. Once the goal was reached, we floundered around for a reason to send people into space.

We now find ourselves within a couple of years of loosing the ability to send Americans into space on our own vehicles. We've spent unbelievable energy and treasure on the ISS which may have to be de-orbited, because it has no real function.

It all happened because there wasn't enough thought given to long-term goals. That is what is lacking in our lives today. We are living for the moment.

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20. Sili on September 16, 2009 10:51 AM writes...

Learn to read, #17.

"can add value"

TomB specifically stressed that it's a very tough job to ensure that the right people are in the right positions. And that is indeed true of any organisation.

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21. CMCguy on September 16, 2009 11:10 AM writes...

#18 IC I think your point(s) about comparisons/horn tooting is good. The missions/focus/environments of academia (where I would place most government labs like NIH) vs industry is very different so should be part of any comparative metrics evaluation, a questionable exercise to begin with. There may be certain overlaps but rather than attempting to take credit/promote achievements what really needs to be encouraged in cooperation and collaborations that link together to produce better advancements overall. Unfortunately both side get so tied up in funding/economics that clouds everything.

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22. molecular architect on September 16, 2009 3:02 PM writes...

#20 (Sili): I read TomB's comments just fine. I agree that it's tough to ensure that the right people are in the right positions. It's his suggestion that "business people and MBAs" are the solution. While anybody CAN add value, I've yet to see a case where the overabundance of these types in most pharma/biotechs DID add value!

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23. milkshake on September 16, 2009 3:28 PM writes...

MBAs are like God: They giveth (= obscene bonuses to among themselves) then they taketh away (= your projects, jobs and careers). You get invited for all hands meeting in the admin building and on the way back everyone is handed a box, with five minutes to pack up the belongings (with the guards standing above you) - they really teach that in the business school.

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24. Anonymous on September 17, 2009 8:08 AM writes...

#23: Do you still do that in America? I thought it was just in movies.

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25. molecular architect on September 17, 2009 8:54 AM writes...

#23: Oh yes, that's how many places do layoffs in the US. Guards walking the hallways making everyone turn off their computers; the group march to HR for your exit interview where you're handed the severance agreement to sign, etc.

I've personally seen it twice, most recently in 2006 at the small San Francisco area pharma where Milkshake and I both worked.

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26. milkshake on September 17, 2009 6:26 PM writes...

that company where we were ought to have been class-action sued by the ex-employees, for being lied to and cheated out of their severance. Since this was all done in completely bad faith, the punitive damage award could have been staggering.

The ex-Sugen employees who got cheated out by Pfizer of their promised severance actually sued and eventually Pfizer settled for what they have been owed (and their legal expenses), but of course there were no punitive damages in this case.

remember, all it takes is a corporate misconduct, two aggrieved former employees, and a hungry law firm. Lawyers are mercenaries - and sometimes one has to hire mercenaries to stand a chance...

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27. srp on September 19, 2009 2:39 AM writes...

I strongly doubt that most business schools have classes on the details of firing people--none of the academics at such schools would have any experience or know much about it. They are way more ivory tower than that--they don't even teach project management (that's left to engineers running certificate programs) as it's too nitty-gritty. The organization and social psych courses that are the main "people management" parts of the curriculum are almost universally the least liked and attended to.

On the other hand, MBAs are drilled hard on avoiding the sunk-cost fallacy and understanding opportunity costs. They are hammered with the idea that if you measure and reward the wrong thing, you'll get the wrong outcomes (there's a famous article with a title like "On the fallacy of rewarding y while expecting x"). Strategy classes impress upon them the importance of not trying to tackle rivals with head-on imitation strategies. So if these pathologies go on in pharma companies, they are in spite of rather than because of MBA training.

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