Corante

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

Chemistry and Drug Data: Drugbank
Emolecules
ChemSpider
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
PubChem
Not Voodoo
DailyMed
Druglib
Clinicaltrials.gov

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
Kilomentor
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
ChemBark
Realizations in Biostatistics
Chemjobber
Pharmalot
ChemSpider Blog
Pharmagossip
Med-Chemist
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
SimBioSys
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Business|Bytes|Genes|Molecules
Eye on FDA
Chemical Forums
Depth-First
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa


Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
FuturePundit
Aetiology
Gene Expression (I)
Gene Expression (II)
Sciencebase
Pharyngula
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net


Medical Blogs
DB's Medical Rants
Science-Based Medicine
GruntDoc
Respectful Insolence
Diabetes Mine


Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem


Politics / Current Events
Virginia Postrel
Instapundit
Belmont Club
Mickey Kaus


Belles Lettres
Uncouth Reflections
Arts and Letters Daily
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« Sulfurous Stenches: A Connisseur's Guide | Main | Merck, So Far »

April 23, 2006

You Can't Win If You Don't Play

Email This Entry

Posted by Derek

I enjoyed one of the recent comments to the "Why All the Gloom" post, where an IP lawyer mentions what people at the small startups told him: namely, that managers had figured out that by saying "No" they were right all the time, while saying "Yes" had a much lower chance of success.

I know just what he's talking about. You can have an entire career in the drug industry, just sitting around telling people that their ideas aren't going to work. And more than nine times out of ten, you'll be right. Fortunetellers and stockpickers should have such a record! So what's the problem?

Well, the problem is, the whole industry depends on those times when someone's idea actually works. For that to happen, chances have to be taken, risks run. Being in charge of reluctantly-killing-off-once-promising-projects has a lot more job security, but someone has to go and make something happen once in a while.

One problem is, I think, that some companies kill things off for a long period until the situation gets more and more desperate. Then they try to run with whatever's in the clinic at the time. Some of those projects will, no doubt, be worse bets than some of the things that were killed off through excess caution a few years before. But if you didn't let a few of those loose, you eventually get stuck with what you have.

That's what's so nerve-wracking about doing pharma research. It's like playing tournament poker: the blind bets keep going up, so if you don't get out there and play some of your hands, you'll be eaten alive. If you convince yourself that none of your cards are worth anything, you're going to have a short night of it. I say, take Francis Crick's advice: don't believe in your own negative arguments so much. Recognize that every experiment, every program, every drug has plenty of reasons why it shouldn't work. Be aware of them, sure - but be aware that everything successful once had the same questions buzzing around it, too. Something has to work - right?

Comments (16) + TrackBacks (0) | Category: Who Discovers and Why


COMMENTS

1. Harry on April 24, 2006 6:49 AM writes...

Of course, the corollary to this is that no FDA bureaucrat ever got in trouble for not approving a drug.

The consequences for approving ANY new drug which is later found to have more or greater side effects than originally thought is being criticised for being lax and not "protecticng" the consumer. The fact that thousands more were helped than hurt by say, Vioxx doesn't figure into the game.

On the other hand, if you DON'T approve a new drug, the worst that can happen is that thousands don't get helped, but those people rarely know about it and thus can't criticise you.

Our society has become totally risk-averse for a variety of reasons. We believe that someone must be responsible for ANY bad outcome, and that we are entitled to be made whole. We no longer accept that sometimes bad things just happen (even to good people). This has had and continues to have enormous economic and moral consequences for our society.

Permalink to Comment

2. Kay on April 24, 2006 7:20 AM writes...

C'mon Harry. Things that have good data get approved. This business is based on luck, and you must get things to clinic to attempt to get lucky. FDA is not inclined to approve junk and CMS is (increasingly) less inclined to pay for it. New mechanisms of action with good clinical data will be hansomely rewarded.

Permalink to Comment

3. Harry on April 24, 2006 7:35 AM writes...

Kay-

Many, many drugs that are on the market today could not get approved today, in fact, they would not even get as far as FDA.

Aspirin is an excellent example. I doubt very much if a molecule with the side effects (GI bleeds and anticlotting properties) of aspirin would even get as far as an FDA application. Even if approved, you can count of such a drug being mobbed by the PI lawyers as was Vioxx (which AFIK had a much better side effect profile).

As I mentioned, there are a number of reasons that society and andustry and the bureaucracy are risk averse- not least of which is the reverse lotto that one runs when putting a product on the market(actually you're making two bets- one, that the product will actually make a profit and two, that it will be safe enough to avoid the attention of the legal system- ONE $100 million verdict wipes out one helluva lot of sales).

My $0.02, YMMV

Permalink to Comment

4. LNT on April 24, 2006 8:57 AM writes...

Derek and Harry (and others) have repeatedly said that aspirin wouldn't be approved today. I'm sure it's true that MANY drugs on the markey today wouldn't be approved in today's system. But what these arguements fail to consider is that technology has improved such that something like aspirin wouldn't be NEEDED today, so it wouldn't be approved based on it's side effect profile. I'm sure the same is true of many ancient chemotherapy drugs. Does anyone want to take a nitrogen mustard chemo agent today? Of course not! But IN ITS TIME it was useful and probably saved or prolonged many lives. But with today's better chemo agents, of course it wouldn't be approved. Same is true of aspirin. Why would the FDA approve an agent that causes GI bleeds when so many other agents are on the market with virtually no side effects?

I would HOPE that aspirin wouldn't make it through the FDA today!!!! If it did, there is something seriously wrong with our drug approval system.

Permalink to Comment

5. Derek Lowe on April 24, 2006 9:50 AM writes...

LNT, that's not an unreasonable way to look at it. But which other aspirin replacements did you have in mind? Acetominophen, which wouldn't have made it through these days, either, due to liver toxicity? The COX-2 inhibitors, which are in the process of being sued off the market?

Aspirin's a weird drug, what with its tangled antiinflammatory/anticlotting/pro-GI bleeding effects. The NSAIDs don't really duplicate it. Finding a single replacement isn't (and hasn't been) easy.

Permalink to Comment

6. tom bartlett on April 24, 2006 9:54 AM writes...

"I would HOPE that aspirin wouldn't make it through the FDA today!!!! If it did, there is something seriously wrong with our drug approval system."

The big problem today isn't with the FDA, but with the tort system. The FDA, if anything is too SLOW.

I am all for consumer protection, but if the FDA, which is careful to a fault, approves a drug, knowing it is not 100% squeeky-clean (like VIOXX, which was known to cause mild edema BEFORE approval), that drug should be very nearly immune from frivolous attacks from greedy lawyers. Unless there are very clear factors that showed the company hid risks they knew about-- which Merck did not.

Permalink to Comment

7. Derek Lowe on April 24, 2006 9:56 AM writes...

The other reason that I bring up the aspirin example is that it's a drug that the general public tends to regard as about the safest thing in the world (acetominophen, too, for that matter). Whereas Vioxx, for example, is being portrayed as a deadly poison, unleashed on the world by a heartless drug company.

I think that if aspirin and acetominophen are our definitions of "safe", then Vioxx is safe, too. And if they aren't safe, then people should realize it, so that they have a fair standard of comparison. As it is now, what the broad public believes about this issue is a mass of contradictions and false impressions, which can't be a good thing.

Permalink to Comment

8. Martin on April 24, 2006 10:04 AM writes...

Harry--can you say AIDS drugs and Act-Up in the late 80s? FDA officials were being burned in effigy for refusing to approve drugs, so I think you're being a little bit near-sighted in regard to the FDA being biased against approval. Another example is Iressa, which the FDA did not want to approve, but hoped that the advisory panel would kill for them... that hardly seems that actions of an institution biased against approving new drugs.

Derek--have you seen any evidence that more people are involved in making go/no-go decisions? I did some back of the envelope calculations a few months ago and it looks like the more people with go/no-go power, the greater the magnification of pre-existing biases towards or against any particular outcome (this is using a majority voting model).

Martin

Permalink to Comment

9. Harry on April 24, 2006 10:13 AM writes...

LNT - then why are we leaving a "dangerous" product like aspirin (and for that matter- acetominophen which is quite toxic to the liver) when we have products that are so much better with regard to side effects?

Would you support withdrawing these older, more dangerous products? Try doing so and listen to the outcry from the very people that are crucifying Merck- it would make the outcry over banning saccharine sound like a minor chord.

There are two reasons why aspirin, for example is still being sold.

First, people have been taking it for many many years and have accepted (actually internalized) the risks associated with the side effects- even though thousands suffer bleeding due to aspirin use each year.

Second, there is no money to be made by suing the makers and sellers of aspirin.

I think we all would agree that aspirin has more problems than Vioxx, and certainly there are more people affected, since practically everyone consumes aspirin, so why is there no hue and cry to take aspirin off the market? Simply because there is no money to be made there.

All drugs have side effects to a greater or lesser extent- I'm generally in favor of approving more drugs and making sure that doctors and patients are aware of the side effects and letting them accept or not accept the consequences. This is not possibly with the tort system of today.

Permalink to Comment

10. RET on April 24, 2006 10:29 AM writes...

Antibiotic research in the pharmaceutical industry is an excellent example but you cant blame the FDA. 38 years went by between unique drugs in this field. During that time Big Pharma cut back all of their expertise.

Problem is still not solved...

Permalink to Comment

11. Harry on April 24, 2006 10:29 AM writes...

Martin- if you'll notice in my original post I said that MOST of the poeple that could be helped rarely know it and can't/don't protest.

Obviously, this is not the case with AIDS and other diseases which have an activist constituency (breast cancer is another example). These people have enough clout to push things along.

Also (and I don't want to make too much of this) AIDS drugs in particular have a strong component of support from people that would be critics of FDA approving a drug with the side effects of, for example a protease inhibitor for some other disease (Henry Waxman for instance).

I think in general disease lobbies can change the risk/reward calculus of the FDA by providing a counterweight to the tendencies I noted in my first post.

Now- I think I need to sit back and try to get some work done today.

Permalink to Comment

12. Jonathan Gitlin on April 24, 2006 10:55 AM writes...

I think that if aspirin and acetominophen are our definitions of "safe", then Vioxx is safe, too. And if they aren't safe, then people should realize it, so that they have a fair standard of comparison. As it is now, what the broad public believes about this issue is a mass of contradictions and false impressions, which can't be a good thing.

Unfortunately, people regard heart attacks (sudden death) as more serious than GI bleeds (slow, lingering death?). Hearing that "Joe down the street dropped dead of a heart attack" has more of an impact than "Mary, Betsy and Sue are all on PPIs and having endoscopes". But the GI risks of low dose aspirin can be mitigated with PPIs, and if you're going to take a PPI anyway, then why bother with an expensive coxib - just take ibuprofen or naproxen and get the same relief from arthritis, plus you don't unbalance the TXA2:PGI2 ratio. To paraphrase a shampoo advert, "why take three pills in the shower when you only have to take two, and save a bundle?"

Still, as a young scientist who's spent the first 8 years of his career working on COX-2, it's a bit irritating to see my field being litigated out of existance.

Permalink to Comment

13. Idol on April 24, 2006 12:05 PM writes...

Great advice for life as well!

Permalink to Comment

14. Finance Man on April 24, 2006 12:21 PM writes...

"Our society has become totally risk-averse for a variety of reasons. We believe that someone must be responsible for ANY bad outcome, and that we are entitled to be made whole. We no longer accept that sometimes bad things just happen (even to good people). This has had and continues to have enormous economic and moral consequences for our society."

What a difference an occupation makes! As a money manager, I can easily show you the mirror image: Our society has become totally risk-seeking for a variety of reasons. We believe that no one must be responsible for ANY wealth creation to occur, and that we are entitled to be made whole with a profit. We no longer acknowledge that sometimes bad things just happen (even to good people). This has had and continues to have enormous economic and moral consequences for our society. Specifically, we all believe that the Federal Reserve will never, never say no to easing credit and bailing out so many investors who have taken on so much risk and debt.

While the FDA may be risk averse, our Federal Reserve and Treasury (think of our fiscal condition) is totally risk taking.

Permalink to Comment

15. IP Person on April 28, 2006 1:14 AM writes...

Hi, yes, it was my prior post. (Just posted about the Ariad patent matters in another thread).

Yes, that researcher's remarks really hit a nerve with me, too, even after all these years.

Ducking the hard decisions, then -- upping the ante on really risky decisions because desperate times call for desperate measures. Why does the song "Instant Karma" come to mind?

Some comments:

Jonathan Gitlin: Please stay the course, we need smart people like you. Not to litigate VIOXX here, but...IMO...it looks like the management decision that to put a warning on the label would be bad (e.g., not make the numbers) was far riskier than the perhaps earlier decisions which kept the pipeline empty. If there were a warning on the label, no lawsuits. (I'm assuming the adverse effects are not junk science, and in no way mean to re-litigate here, only using this as an illustration).

I wonder if there is an employee class action for negligent management? Joke. Sort of.

Finance man: The problem to me is not the entitlement of investors, but the entitlement attitude of the executive suite.

Thanks again for the blog, IP Person


Permalink to Comment

16. mahjong dark dimensions for mac on June 20, 2013 9:29 AM writes...

Thanks for this post, I am a big fan of this internet site would like to continue updated.

Permalink to Comment

POST A COMMENT




Remember Me?



EMAIL THIS ENTRY TO A FRIEND

Email this entry to:

Your email address:

Message (optional):




RELATED ENTRIES
A Last Summer Day Off
The Early FDA
Drug Repurposing
The Smallest Drugs
Life Is Too Short For Some Journal Feeds
A New Look at Phenotypic Screening
Small Molecules - Really, Really Small
InterMune Bought