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About this Author
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

« AstraZeneca Says No Again | Main | Where the Talent Comes From »

May 19, 2014

AstraZeneca Looks At Its Own History, And Cringes

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Posted by Derek

While we're talking about AstraZeneca, here's a look at their recent drug development history from the inside. The company had undertaken a complete review of its portfolio and success rates (as well they might, given how things have been going overall).

In this article, we discuss the results of a comprehensive longitudinal review of AstraZeneca's small-molecule drug projects from 2005 to 2010. The analysis allowed us to establish a framework based on the five most important technical determinants of project success and pipeline quality, which we describe as the five 'R's: the right target, the right patient, the right tissue, the right safety and the right commercial potential. A sixth factor — the right culture — is also crucial in encouraging effective decision-making based on these technical determinants. AstraZeneca is currently applying this framework to guide its R&D teams, and although it is too early to demonstrate whether this has improved the company's R&D productivity, we present our data and analysis here in the hope that it may assist the industry overall in addressing this key challenge.

That already gets things off to a bad start, in my opinion, because I really hate those alliterative "Five Whatevers" and "Three Thingies" that companies like to proclaim. And that's not just because Chairman Mao liked that stuff, although that is reason enough to wonder a bit. I think that I suffer from Catchy Slogan Intolerance, a general disinclination to believe that reality can be usefully broken down into discrete actions and principles that just all happen to start with the same letter. I think these catchphrases quantify the unquantifiable and simplify what shouldn't be simplified. The shorter, snappier, and more poster-friendly the list of recommendations, the less chance I think they have of being any actual use. Other than setting people's teeth on edge, which probably isn't the goal.

That said, this article itself does a perfectly good job of laying out many of the things that have been going wrong in the big pharma organizations. See if any of this rings a bell for you:

. . .However, with the development of high-throughput and ultra-high-throughput screening and combinatorial chemistry approaches during the 1980s and 1990s, as well as the perception that a wealth of new targets would emerge from genomics, part of this productivity issue can also be attributed to a shift of R&D organizations towards the 'industrialization' of R&D. The aim was to drive efficiency while retaining quality, but in some organizations this led to the use of quantity-based metrics to drive productivity. The hypothesis was simple: if one drug was launched for every ten candidates entering clinical development, then doubling or tripling the number of candidates entering development should double or triple the number of drugs approved. However, this did not happen; consequently, R&D costs increased while output — as measured by launched drugs — remained static.

This volume-based approach damaged not only the quality and sustainability of R&D pipelines but, more importantly, also the health of the R&D organizations and their underlying scientific curiosity. This is because the focus of scientists and clinicians moved away from the more demanding goal of thoroughly understanding disease pathophysiology and the therapeutic opportunities, and instead moved towards meeting volume-based goals and identifying an unprecedented level of back-up and 'me too' drug candidates. In such an environment, 'truth-seeking' behaviours to understand disease biology may have been over-ridden by 'progression-driven' behaviours that rewarded scientists for meeting numerical volume-based goals.

Thought so. Pause to shiver a bit (that's what I did - it seemed to help). The AZ team looked at everything that had been active during the 2005-2010 period, from early preclinical up to the end of Phase II. What they found, compared to the best figures on industry averages, was that the company looked pretty normal in the preclinical area (as measured by number of projects and their rates of progression, anyway), and that they actually had a higher-than-usual pass rate through Phase I. Phase II, though, was nasty - they had a noticeably higher failure rate, suggesting that too many projects were being allowed to get that far. And although they weren't explicitly looking looking beyond Phase II, the authors do note that AZ's success rate at getting drugs all the way to market was significantly lower than rest of the industry's as well.

The biggest problem seemed to be safety and tox. This led to many outright failures, and to other cases where the human doses ended up limited to non-efficacious levels.

During preclinical testing, 75% of safety closures were compound-related (that is, they were due to 'off-target' or other properties of the compound other than its action at the primary pharmacological target) as opposed to being due to the primary pharmacology of the target. By contrast, the proportion of target-related safety closures rose substantially in the clinical phase and was responsible for almost half of the safety-related project closures. Such failures were often due to a collapse in the predicted margins between efficacious doses and safety outcomes, meaning it was not possible to achieve target engagement or patient benefit without incurring an unacceptable safety risk.

On top of this problem, an unacceptable number of compounds that made it through safety were failing in Phase II though lack of efficacy. There's a good analysis of how this seems to have happened, but a big underlying factor seems to have been the desire to keep progressing compounds to meet various targets. People kept pushing things ahead, because things had to be pushed ahead, and the projects kept being scooting along the ground until they rolled off into one ravine or another.

And I think that everyone with some experience in this business will know exactly what that feels like - this is not some mysterious ailment that infected AstraZeneca, although they seem to have had a more thorough case of it than usual. Taking the time to work out what a safety flag might be telling you, understand tricky details of target engagement, or figure out the right patient population or the right clinical endpoint - these things are not always popular. And to be fair, there are a near-infinite number of reasons to slow a project down (or stop it altogether), and you can't stop all of them. But AZ's experience shows, most painfully, that you can indeed stop too few of them. Here's a particularly alarming example of that:

In our analysis, another example of the impact of volume-based goals could be seen in the strategy used to select back-up drug candidates. Back-up molecules are often developed for important projects where biological confidence is high. They should be structurally diverse to mitigate the risk for the programme against compound-related issues in preclinical or early development, and/or they should confer some substantial advantage over the lead molecule. When used well, this strategy can save time and maintain the momentum of a project. However, with scientists being rewarded for the numbers of candidates coming out of the research organization, we observed multiple projects for which back-up molecules were not structurally diverse or a substantial improvement over the lead molecule. Although all back-up candidates met the chemical criteria for progression into clinical testing, and research teams were considered to have met their volume-based goals, these molecules did not contribute to the de-risking of a programme or increase project success rates. As a consequence, all back-up candidates from a 'compound family' could end up failing for the same reason as the lead compound and indeed had no higher probability of a successful outcome than the original lead molecule (Fig. 6). In one extreme case, we identified a project with seven back-up molecules in the family, all of which were regarded as a successful candidate delivery yet they all failed owing to the same preclinical toxicology finding. This overuse of back-up compounds resulted in a highly disproportionate number of back-up candidates in the portfolio. At the time of writing, approximately 50% of the AstraZeneca portfolio was composed of back-up molecules.

I'm glad this paper exists, since it can serve as a glowing, pulsing bad example to other organizations (which I'm sure was the intention of its author, actually). This is clearly not the way to do things, but it's also easy for a big R&D effort to slip into this sort of behavior, while all the time thinking that it's doing the right things for the right reasons. Stay alert! The lessons are the ones you'd expect:

An underlying theme that ran through the interviews with our project teams was how the need to maintain portfolio volume led to individual and team rewards being tied to project progression rather than 'truth-seeking' behaviour. The scientists and clinicians within the project teams need to believe that their personal success and careers are not intrinsically linked to project progression but to scientific quality, smart risk-taking and good decision-making.

But this is not the low energy state of a big organization. This sort of behavior has to be specifically encouraged and rewarded, or it will disappear, to be replaced by. . .well, you all know what it's replaced by. The sort of stuff detailed in the paper, and possibly even worse. What's frustrating is that none of these are new problems that AZ had to discover. I can bring up my own evidence from twelve years ago, and believe me, I was late to the party complaining about this sort of thing. Don't ever think that it can't happen some more.

Comments (46) + TrackBacks (0) | Category: Clinical Trials | Drug Development | Drug Industry History


COMMENTS

1. Anonymous on May 19, 2014 8:44 AM writes...

All very nice and I can relate from my own experiences what is being disucussed, but we know that back at the coalface the 'old behaviours' will eventually win as the pressure comes down from the top.

Permalink to Comment

2. bhip on May 19, 2014 8:47 AM writes...

All of this is very familiar. Everyone's organizational bonus + year end review (ramifications ranging from bonus to being shown the door) based on barfing up a certain # of candidates for clinical development. As the 4Q grinds to a close, the (not very lofty) standards for advancement descend closer to the bottom of the barrel....
Incentivize drug discovery teams for passage of compounds into Ph3 & really reward passing through Ph3 (GSK does this?). As greed drives our current system, let greed drive a better one.

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3. Piero on May 19, 2014 9:22 AM writes...

Shoudn't something like "the five R's" be actual words beginning with R and not the same R-adjective repeated?
This kind of stuff is already laughable if done right but in this way turns absolutely silly

Permalink to Comment

4. Argon on May 19, 2014 9:41 AM writes...

Four "W"s...
Welease Woger! Welease Bwian!
http://www.youtube.com/watch?v=AX0XDHF3M60

Permalink to Comment

5. watcher on May 19, 2014 9:46 AM writes...

"Truth" is often not rewarded, and those who raise an awareness can be easily considered "difficult" or "obstructionist". This occurs even after the person is proven to be correct, as it can get in the way of others' "image" or "political positioning". Any company, as a collection of competitive people, will have an amount of non-scientific, truth begone, driven decisions. Large "science" based companies are not averse to this; desperate companies are even more-so complicated.

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6. Anon on May 19, 2014 9:55 AM writes...

It must be difficult to get people focused on 'truth seeking' if they know they are likely to have retired by the time that the truth is known, but in the meantime they can do very well by hitting the metrics or IPO-ing their ideas.

Contrast the "golden age" of drug discovery (~1935 to ~1970) with the situation today. In the golden age, innovation was dominated by the interaction between medicinal chemists (mainly in industry) and clinical scientists. These people would: (a) Have lived through the Great Depression and World War 2, which may have given a different sense of perspective and priorities; (b) Have seen the clinical fruits (or failures) of their labours quickly, given low regulatory barriers to human testing and the acute nature of much untreated disease; (c) Have had relatively modest financial incentives to climb the corporate ladder, given narrow (~10x) pay differentials between CEO and scientist remuneration; And (d), found it hard to get rich by setting up a 'biotech' type company.

Contrast this with 2014 where: (a) 'Greed is good'; (b) It may take half a working lifetime (~20 years?) to find out if a discovery has clinical utility; (c) The average S&P500 chief executive salary is several hundred times higher than the average medicinal chemist salary; (d) And the VC and IPO markets mean that plausible stories can be monetized by and entrepreneurial scientists long before anyone knows whether or not they are true.

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7. commenter on May 19, 2014 9:56 AM writes...

FYI Derek a new post on the training crisis in med-chem is up on the lifescivc blog and begging for your commentary

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8. Justin on May 19, 2014 10:10 AM writes...

"Back-up molecules...should be structurally diverse to mitigate the risk for the programme against compound-related issues in preclinical or early development"

I'd still be in Pharma if this one hadn't bit me in the ass.

Permalink to Comment

9. Morten G on May 19, 2014 10:24 AM writes...

Sounds like the authors are fans of your blog, Derek ;)

Question:
How large a proportion of a pharma workers salary is tied into bonuses for hitting metrics?

Permalink to Comment

10. Ex consultant on May 19, 2014 10:32 AM writes...

Regarding the 5 or 6 "R"s, I am reminded of my old management consulting days. The criterion that we used to apply, when either doing a diagnosis or a strategy, was whether or not the important thingies could be written on a graphic of an ancient Greek temple.

In this case, I would have recommended a nice picture of a temple with a base (aka “stylobate”) on which is written "THE RIGHT...", surmounted by five Doric columns, bearing the words "TARGET", "TISSUE", "SAFETY","PATIENT" and "COMM. POT." "COMM. POT." has to be shortened from “COMMERCIAL POTENTIAL” otherwise the pillar will be too tall and the whole thing will fall over. These should then be surmounted with a triangular pediment that says "CULTURE".

If, for some reason, the client did not like temples, the more expensive option was draw things on a wheel instead. In this example, I would swap the axle for the stylobate, the pediment for the tyre, and the spokes for the Doric columns.

Given AstraZeneca’s negative stock price move today, I am prepared to waive my consulting fee for this advice.

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11. Curt F. on May 19, 2014 10:34 AM writes...

Failure is an inescapable part of drug discovery. No one disputes that. In this study, authors propose that steps where AZs failure rate is higher than the industry average indicate *upstream* steps that aren't being culled enough.

Why don't pharma R&D managers provide incentives for greater culling? Instead of incentivizing workers solely for projects that are passed forward, shouldn't the give out bonuses for projects that workers want to cancel?

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12. alig on May 19, 2014 10:34 AM writes...

At one big pharma, candidates nominated in Q1-Q3 had about double the chance of success as candidates nominated in Q4. The heads of the disease areas had huge incentives to meet their numbers. Who cares if the candidates fail later, those guys will be at a different company by the time the reckoning comes.

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13. DrSnowboard on May 19, 2014 10:38 AM writes...

And then , in the final paragraphs they say "Our ambition is to achieve an overall success rate of at least 8% from preclinical GLP toxicology to launch." So the response to a diatribe on the failure of metrics or 'you get what you measure' is to set ....another numerical metric.... Of course, they will be slightly preoccupied with the metrics of being swallowed by Pfizer for the foreseeable future so this is an interesting stick drawing in the sand, but will suffer the same fate.

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14. Validated Target on May 19, 2014 10:55 AM writes...

@5 watcher (and others): "truth", punished not rewarded. I've had that happen to me too many times. That always made me the Validated Target. (That is, I would raise Qs, point out problems or provide contrary results, etc, in re: ongoing crappy projects. My own projects were never advanced, perhaps because I didn't misrepresent them.)

I am surprised that AZ allowed the authors to submit and publish this article. But I'm glad they did.

ALSO: THE PROBLEM WITH INCOMPLETE PAGE LOADS AND DISAPPEARING COMMENTS HAS RETURNED. PLEASE FIX!

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15. DrSnowboard on May 19, 2014 11:11 AM writes...

@10 I have indeed suffered graphics in the shape of a temple. I think The Five Pillars of Drug Discovery may indeed have been shown this way, in garishly stupid colours , or perhaps that was the performance management / cultural change graphic? Anyhow, I'm pleased you got paid for turning out such mindless drivel. It got filed in a direct fashion, accompanied by scathing laughter

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16. Anonymous on May 19, 2014 11:12 AM writes...

@14, Validated Target: I can sympathize. When results from an assay come back and it's obvious that a compound shouldn't proceed and Qs are raised, words like "difficult" and "bad attitude" and "need to be more positive" come about. Meanwhile people who smile and nod their head are favored, even when in the end the compound is finally shelved.

Is there a remedy to this situtation? Does it occur to this extent in the tech industry? I'm genuinely curious since I have never worked anywhere but pharma/biotech

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17. Biff on May 19, 2014 11:15 AM writes...

I imagine the authors of the AZ article deciding to write the article while sitting in a room that feels like a more subdued version of one of those bridge scenes from the original Star Trek series where someone shouts, "Captain! We can't take another hit! The warp core is going to blow!", and the captain calmly orders, "Download ship's logs to the emergency buoy. Launch buoy!!"

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18. Biff on May 19, 2014 11:37 AM writes...

@16 - Yes, it does happen in the tech industry, particularly with "big bang" products. Windows 8 is probably the biggest recent example, or perhaps the various Affordable Care Act healthcare exchanges. To be fair, though, most tech industry projects have much shorter life cycles, so problems with viability tend to become clear much more quickly than problems with drug candidates, and the cost of a failed project is usually much less than a failed Phase 3 clinical trial.

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19. Dr. Manhattan on May 19, 2014 11:38 AM writes...

Biff @17,18, &19. Is this the episode where the Enterprise D is caught in a repeating time loop?

Yes, this was written by senior management types at AZ. But indeed the behavior of moving compounds forward under pressure is a common problem. In my last company, we had an assigned "Project Manager" (non-scientist) who would generate Gantt charts on the project time lines & intermediate goals. "Hey, the charts say that you are scheduled to be scaling up for animal tox by this point!" Never mind that the compound already had a liver signal that needed to be addressed. The rewards were not for "truth seeking" .

I was also at a "Five Pillars" company. Round up the usual consultants and have them make a simplifying set of "guidelines" that supposedly encapsulates the keys to Drug Discovery.

Permalink to Comment

20. Eric on May 19, 2014 11:39 AM writes...

@14: If you look at the author list, you will see that one of them is the head of R&D at AZ, and sits on the board. It's good to see him hitting his own metric of everyone with a PhD writing a paper a year.

Permalink to Comment

21. Anonymous on May 19, 2014 11:45 AM writes...

@5 and others, this is all too accurate. Contrary to the fairy tale we were told as children, the emperor does not appreciate being told he/she has no clothes, and the other peasants will shun you rather than acclaim you for poniting out what they also knew was true...

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22. Cellbio on May 19, 2014 11:46 AM writes...

@Morten

I was a manager of a discovery group during an exact copy of this numbers game. Bonuses were rich then, with my own running at 50% of my base, Scientists running ~30% and the associates ~20%. It was such a big part of the culture that everyone knew to the dollar what they should get once the corporate and department performance against metrics were announced that any slight adjustment from the "target" bonus to reward those that deserve it, like the ones actually at the bench, would cause folks who were 'short' a few hundred bucks to complain. The bonus pay became as expected as base pay and more central to strategy and execution than discovering cures.

@Curt, incentives for killing programs was tried too. If anything, this was worse because teams of scientists, naturally skeptical and conservative, were rewarded for pointing out every potential reason why something might fail and deciding not to move forward. Really perverse period where team leaders would stand in front of review boards saying with great pride and enthusiasm how they had not done a good enough job to move forward. Thankfully, this went away quickly.

What is lost is the setting of goals to have a body of work, the disparate activities that come together in a project, inform the prospects of success, and have that new information re-inform the investment thesis. Every program starts with a justification, target, technical feasibility, medical and market opportunities, that has a basis of knowledge that shifts during execution. The target theory may be good, but does the chemistry developed give you the opportunity to hit 'the target', or a basket of targets. If the latter, re-examine the prospects. Knock-out says one thing, inhibition another? Worse yet, published data not repeated? Clinical data rescued by hunt for responder population? All these and many more handled well by good scientific decisions, each with specifics so narrow that the only goal to be written or metric followed is to make a solid decision when new information enables the decision.

For best research culture we need to abolish performance reviews, abolish goals and metrics associated with performance or compensation and abolish bonuses.

Permalink to Comment

23. MTK on May 19, 2014 11:52 AM writes...

@22 Cellbio,

I believe you rightly point out some of the ways that metrics distort things, essentially because it's easy to incentivize or disincentivize any actions or behaviors.

I'll depart from your view, however, on your last statement regarding the abolition of metrics, bonuses, goals, etc. I think you need them and that they can be effective. However, as we've seen it's not easy, especially in a research setting, to set effective measures. And that's an understatement.

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24. pd on May 19, 2014 11:54 AM writes...

From my own personal experience this article shows that Pfizer and AZ is a match made in heaven

I hope they will be very happy together

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25. bluekirby on May 19, 2014 12:18 PM writes...

@23 MTK
Regardless of what the bonuses or incentives are, people will always find a way to game the system. It's definitely challenging to design a system that encourages the desired behavior. I'm wondering if you have any suggestions for a system that would work? Personally I was thinking a 5% company-wide bonus for each drug that gets FDA approval. That's a metric that everyone is working towards (or at least I hope they are).

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26. dlib on May 19, 2014 12:20 PM writes...

@16
There is a saying in tech "kill the engineer and ship the product". That's because the engineers after having done the first version know they can make it better. The managers know that if the first version is good enough to make a sale then sell it while the engineers are working on the next iteration 2.0. Doesn't translate well into pharma.

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27. Cellbio on May 19, 2014 12:33 PM writes...

MTK,

I agree that metrics and goals can be effective, however, I know from experience that the negatives to an organization associated with tying performance measures and pay to outcomes influenced by some many unknowns are real and outweigh the benefits. Many folks, especially HR, hold an unchallenged belief system that goals are needed to measure performance and bonuses drive company success when experience says the system is always gamed.

Agree with bluekirby, flat bonus across the company for externally valid measure like approval. Base pay already rises, no need to also raise the bonus multiplier.

Permalink to Comment

28. dearieme on May 19, 2014 1:58 PM writes...

It shows that the senior executives had not the first idea of how to manage scientists. What plonkers!

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29. newnickname on May 19, 2014 3:14 PM writes...

@26 "kill engineer; ship product": Reminds me of the Challenger disaster. The engineers said, "Don't launch! Don't launch!" Management said, "Launch!" Challenger blew up and killed the crew ... for the very reasons the engineers predicted.

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30. Sweden Calling on May 19, 2014 3:29 PM writes...

These were terrible times, but to be fair very few scientist complained about the heavy use of metrics. If only the seventh "R" would have been "the right molecule"...?! ; )

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31. Jim on May 19, 2014 4:14 PM writes...

I'm no apologist for management nor a huge fan of metrics, but it's easy to see how we got to where we are. Our culture (not only in business) likes to keep score and reward good performance. The hard part is that in science, good performance does not always lead to a product. But, as near as I can tell, the only "good" way to kill a program is to invalidate the target (which should have been done earlier).

We've all been told to "fail fast, fail soon", but as long as there's chemical space out there, the next development candidate might be out there as well. I've seen plenty of program leaders fight for continued, additional resources because they only need to improve bioavailability, or half-life... A bit of a Catch-22.

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33. milkshake on May 19, 2014 4:50 PM writes...

Fucking mismanagement. Slick mountebanks and hochstaplers, arrogant cretins and toadies - all the way to the top. These people draw obscene salaries and bear no consequence for plowing under the company research, in their group-think obsession with "blockbuster" projects, incessant idiotic open office - vertical silos - lean sigma - black belt reorganizations, and through destructive acquisitions. They are throwing money at the latest fad wishfully hoping that there *must* be sure and risk-free shortcut to billion dollar drug because they plained it out so in their slides, and already promised to the shareholders last year when they got the job. The truth is, no matter what they did to the research, the consequences start showing maybe 5 years later, and it is hard to pinpoint what could have been, but was lost. And there is always the collective irresponsibility and corporate scapegoating. The demoralization of research staff, who a are often treated like a commodity, or a shapeless concrete sludge (poured into perfectly laid organization structure), who are lied to periodically and live in constant fear of layoffs is what brings down the company down over the long run. How many drugs came from Groton? And how many from Sandwich? And guess what happened to Sandwich...

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34. Rock on May 19, 2014 6:24 PM writes...

@24 pd
Couldn't agree more. If the name of the company was redacted I would have sworn it was written by Pfizer.
@33 milkshake
Agree that productivity is never considered in making site closure decisions. Although in the end, Groton's role has changed significantly in recent years, and the majority of management in Cambridge (in chemistry at least) are ex-Sandwich blokes.

Permalink to Comment

35. Nick K on May 19, 2014 7:34 PM writes...

#33 Milkshake: Nail on the head. The people responsible for this debacle have done extremely well out of it, and are now safely ensconced in senior positions in other companies or are retired to their Florida condos. The poor grunts who actually do the work at the bench have really suffered.

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36. 5s on May 19, 2014 9:02 PM writes...

5s.... shit, shit, shit, shit and shit

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37. Anonymous BMS Researcher on May 19, 2014 10:24 PM writes...

@Ex consultant: I forget the topic and the slogan, but I do actually recall seeing some sort of Greek Temple graphic at BMS a few years ago.

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38. Kaleberg on May 20, 2014 12:05 AM writes...

I did some research on incentives in the Soviet economy in the early 1970s, and some of the stuff about metrics and bonuses is all too scarily familiar. At the extreme, there were the stories of taxi or delivery drivers paid by the mile who would jack up their vehicles and let the wheels spin while they did serious work sampling vodka. More common were the little games of manipulating the timing, compounding rounding errors and ignoring issues like quality or even usability.

The USSR's problem seemed to be that the folks in charge were managers with no clue and no real care about actually getting things done. They could shop in dollar stores. People used to make jokes about MBAs, but in the US (and the rest of the first world) stuff still seemed to get done.

I'd like to imagine that the problem is only in pharma, but with Walmart unable to restock its shelves, one has to wonder. Who did win the Cold War?

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39. London_Chemist on May 20, 2014 2:29 AM writes...

@33
Sandwich WAS a very productive site: Diflucan, Voriconazole, Doxasosin, Norvasc, Maraviroc, the Big Blue pill.
BUT, something changed ~late 90s?. Change of management, more pressure to succeed from corporate? I'm sure a lot people have a lot of theories. But I think metrics and the Dog eat Dog atmosphere (individuals were successful not teams) didn't help....

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40. AKF on May 20, 2014 3:07 AM writes...

I was enjoying this post till I read @20 that one of the authors is head of R&D. Call me cynical but for me that undermines the paper so far as being an unbiased record of what happened in AZ, even if it sounds plausible...

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41. Anonymous on May 20, 2014 3:50 AM writes...

"Not everything that can be counted counts, and not everything that counts can be counted." This quote, frequently mis-attributed to Einstein, is apt nonetheless.

BTW, did you, #33 Milkshake, ever work @GSK?

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42. BeenThereDoneThat on May 20, 2014 7:41 AM writes...

Well Dr. Pangalos learns his lessons well. He was one of the proponents of "quantitative" innovation at Wyeth and as such did very well in setting the standard to achieving just the right number of compounds at the end of the year to make the bonus metric. The analysis reported in the article is nothing more than an update of the analysis that was done over and over again at Wyeth with no effect. Maybe this time it will be different under the umbrella of a different management structure. I also wish Seinfeld would come back..we can hope can't we.

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43. UK Chemist on May 20, 2014 12:56 PM writes...

Not all have retired to Florida. One is alive and well and running R&D at Lilly

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44. Dr Siegfried Sassoon on May 20, 2014 5:14 PM writes...

For the record, the data grunt work behind this definitive proof of the b. obvious took significant time and effort by a significant number of unacknowledged AZ scientists, deemed of significant enough short term value to dig trenches but of no long term value whatsoever, just like the site where 12 significant drugs have been discovered in 57 years.

Funny old world...

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45. Anonymous on May 21, 2014 9:20 AM writes...

In fact, the five 'R's can be categorized in two aspects. The target, the tissue and the safety represent one aspect; the patient and the market represent the second one. Obviously, it is the first aspect related issues put the productivity down. And if one can compare their case with other companies, you can easily identify what is wrong!

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46. Anonymous on May 21, 2014 9:22 AM writes...

In fact, the five 'R's can be categorized in two aspects. The target, the tissue and the safety represent one aspect; the patient and the market represent the second one. Obviously, it is the first aspect related issues put the productivity down. And if one can compare their case with other companies, you can easily identify what is wrong!

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