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In 2010, in my blog, DrugBaron, I declared the death of incremental innovation and wrote the obituary. It didn’t seem a very bold statement at the time - increasing payor pressure was beginning to bite, and it seemed obvious that the entrenched practice of paying a premium for small (often imperceptible) improvements ... |
If payors, whether governments, private insurers or even patients, were unwilling to pay for incremental innovation, then the inescapable logic seemed to be that the industry would have to stop developing such products, and instead seek bigger improvements in clinical performance. |
But three years later, the market for late-stage products that show little, if any, differentiation remains as frothy as it has ever been. As if to prove the point, Astrazeneca invested a little over a billion dollars in two such products in one month: another LABA combination from Pearl, and another prescription fish... |
With deals like this on the table, why not develop another me-too product against a well-validated human target? After all, the technical risk is very low. So as long as you as are confident someone will acquire the product, it looks like an excellent investment. |
In common with Mark Twain, then, reports of the death of incremental innovation were clearly exaggerated. |
How then can you square the circle? If payors increasingly refuse to pay for incremental innovation (even before 'pay for performance' really takes off, as it surely will), yet pharma companies are paying big bucks for poorly differentiated products then someone has to be making a costly error. |
The answer is that pharma companies (or some of them at least) are using their gargantuan balance sheets to absorb the pressure from payors, rather than transmitting it to the early stage discovery efforts (whether internally or externally). While they continue to buy poorly differentiated late-stage products, the dri... |
The big question has to be why do they do it? |
After all, it is a strategy that is likely to end badly. If you fill a pipeline with products displaying little real innovation or improvement in outcomes against a landscape where increasingly no-one will pay for such products then you are setting yourself up for catastrophic failure. You can only ignore the demands... |
But that failure is a long time coming. And if you are very big, it could be a decade or more away. It seems that there are much more short term concerns that demand action - and lead to behaviours that are ultimately close to suicidal. |
Elias Zahouni, the eloquent R&D chief at Sanofi recently hinted at the underlying cause of these conflicting behaviours: large pharma companies are principally motivated by fear, and expend 90% of their effort on defending existing revenues rather than on generating new sources of income. Such defence is prudent and n... |
This defensive attitude causes pharma to acquire products that are less risky (and hence less innovative) than their customers are demanding. That is a very dangerous mis-match - and one that becomes more severe the emptier the pipeline is perceived to be. |
For a publicly-traded company, the spotlight falls heavily on the late-stage pipeline. And bad news translates quickly into a falling market cap. Faced with a choice of two kinds of bad news - a Ph3 clinical trial failure or the failure of a product to win a substantial market (products that I have previously called ... |
Far better, then, to acquire a product with so little innovation that it can hardly fail to be approved - and then sweat about whether payors will actually pay for it in any kind of volume - than it is to acquire a genuinely innovative, first-in-class product and then discover it has feet of clay. |
And the more your innovative bets tumble (as Lilly as experienced recently), the greater the pressure on the executives to flex the balance sheet and acquire "safe" bets. |
The result will surely be a viscous downwards circle, where acquisitions of undifferentiated products that cannot fail in the clinic leads to too few sales to justify the purchase price. There has to be a very real risk that some large pharma are already uncomfortably close to this 'death spiral'. |
Avoiding this fate isn't just about taking more risk, even if the public market investors would tolerate it. The industry has to get smarter at taking these risks. Right now, too many innovative first-in-class programmes are failing in Phase 3. |
The problem is not that real innovation is risky - of course it is. But a way has to be found to fail these programmes much earlier. I have already examined the factors that led several pharma companies to progress anti-amyloid drug candidates into Phase 3 (and indeed to keep on trying) when all the data (even from P... |
Taking the risks necessary to deliver real advances in patient care are only economic if the discovery and development costs can be shrunk - not just 20-30% as has been widely accepted across the industry but by two-fold or even more. |
That kind of cost reduction cannot be achieved by evolving the old model - a model that in any case grew in a very different world: a world of 'gold rush economics' where any approved drug automatically garnered sufficient sales to justify discovering a new drug at any price. Discovery was optimised for success not pr... |
A change in the way we design and interpret Phase 2a studies, the key gatekeeper in the drug development process, lying between relatively low cost early development and the mega-bucks of late stage, is the most pressing need. Studies must be able to distinguish those products that will succeed, not just in later deve... |
Yet again, though, the conservative mindset in large companies makes such changes difficult. If a study is borderline, or yields a grey result, its better to keep the pipeline full and delay the bad news for another day. After all, it might work. |
And its not just large companies. The defensive mindset can permeate even the smallest operations if the management feel that their jobs, or even their careers, are in peril should the product they are developing fail. The incentive to delay failure, until later in development, or even into the marketplace, are very ... |
So, incremental innovation is alive and well. Even as it’s starved of oxygen by the tightening purse strings of the eventual customers, it is being sustained by the stronger imperative to avoid clinical failures, or any kind of imminent bad news, by pharma companies who failed to grasp the need to change to a leaner d... |
Only they will survive. Any that are caught in the trap of doing low-risk incremental innovation when the customer demands a step-change in outcomes, defying logic through the sheer power of their balance sheets built up on historical successes, will end up completely drained. |
For early stage investors, then, there is a real conundrum - should they back poorly differentiated products because they offer good returns at lower risk as long as pharma keep buying? That depends on how long the largest companies continue to use their financial muscle to warp reality. I was three years too early c... |
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Does Antimatter Fall Up? 255 |
Posted by Soulskill |
Does Antimatter Fall Up? |
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• by Electricity Likes Me (1098643) on Tuesday April 30, 2013 @04:51PM (#43595373) |
Obviously there must be some credence to this idea for such an experiment to take place, but since my understanding is that gravity is an inherent effect of mass warping space, wouldn't anti-matter possess mass in the same way that matter does, so why would gravity act differently? |
Just asking. Not trying to claim anything. |
Inertial mass and gravitational mass are observed - for normal matter - to be exactly equivalent. There's no actual reason they should be though, since they're the product of very different interactions - it's perfectly logical to have something which "weighs" a 1000kg when experiencing electromagnetic acceleration... |
For normal matter, this is the case. For antimatter it's presumed but not actually tested, and therein lies the rub. Even a slight deviation would be huge - and have big implications for the question of why the universe has so much matter in the first place. |
• by ceoyoyo (59147) on Tuesday April 30, 2013 @05:13PM (#43595579) |
Scientists like upsets. They wouldn't BE upset, it would be an upset. |
• by Charliemopps (1157495) on Tuesday April 30, 2013 @05:44PM (#43595893) |
Because these are individual atoms. Very hard to detect unless they are clumped together as a mass... as in the millions. The only way to know their position is to force them to be where you want them via a magnetic field... etc... which ruins your chances of measuring any gravitational effect which is unfathomably... |
• by jmv (93421) on Wednesday May 01, 2013 @12:42AM (#43598097) Homepage |
Anti-matter still has a positive mass. Otherwise when a positron meets an electron it wouldn't release any energy. Personally, I highly doubt it "falls up", as that would be inconsistent with general relativity because anti-particles would not follow a curved space. What would be really cool is if it was found that... |
• by Anonymous Coward on Wednesday May 01, 2013 @04:39AM (#43598743) |
You are in that strange paradox of a state in which you know too much, but also too little about physics. |
Your code should be more efficient! |
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Capitals vs Rangers |
Why the Rangers will win the Stanley Cup |
By Dan Rosen - NHL.com Senior Writer |
If the Los Angeles Kings did it last year, the New York Rangers can this year. |
Familiar Foes |
By Corey Masisak and Dave Lozo |
For the third straight year, the Capitals and Rangers meet in the postseason. NHL.com provides a complete head-to-head breakdown. |
That's the Rangers' rallying cry, right? It should be. There's reason to believe in it. It actually makes a lot of sense. |
The Rangers battled their own inconsistent play all season, much in the same way the Kings did last season. Both were considered locks for the Stanley Cup Playoffs before the season started but didn't clinch until the regular season was down to few days remaining. |
The Kings made it as the eighth seed in the Western Conference with 95 points in 82 games; the Rangers got in this season with 56 points in 48 games, qualifying as one of the final three teams in the East during the week's final season. The points-per-game average between the teams was almost identical, as well. |
Wait, there's more. |
The Kings had (and still have) high-end talent in their top-six, enough grinders who could be offensive threats in their bottom-six, a fairly stout defense, and an all-world goalie. |
Ditto for the Rangers this season, especially in goal with Henrik Lundqvist. |
The Kings were hot going into the playoffs last season, 9-2-3 with 41 goals scored over their last 14 games of the regular season. The Rangers are hot going into the playoffs this season having gone 10-3-1 with 51 goals in their last 14 games. |
The comparisons stop there because what the Kings did in the playoffs last season, when they took a 3-0 lead in all four rounds and went 16-4 overall to win the Stanley Cup, isn't likely to be matched any time soon. The Rangers can't be expected to do that, but they don't have to try to be the Kings because they're goo... |
They're experienced. They grind. They defend well. They trust their goalie. They have the potential to excel on the penalty kill. And, throughout April, they were scoring enough too. |
The Kings did it last year; the Rangers will do it this year. |
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Why Deism and Corrupt Government Don"t Mix |
It's been my experience when talking to people about religion, that the overwhelming majority of them have never heard of Deism. Hopefully, with the recent conversion of world-famous philosopher and atheist, Antony Flew, to Deism, this will begin to change. The lack of knowledge of Deism is highly unusual given the str... |
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To Coachman With Love: Pinocchio and Behavioral Therapy |
[Enjoy this guest post from Melanie Englert, boys and girls! - Ed.] |
“Give a boy enough rope and he’ll soon make a jackass of himself!” |
So says the Coachman, the supposed antagonist in Disney’s animated classic, Pinocchio. Everyone knows the tale of Pinocchio and his well documented but poorly understood nasal malady. A lovable woodcarver named Geppetto, having never sired a child of his own and conveniently aware of this missed opportunity just as the... |
Pinocchio embarks on a series of misadventures (including a run-in with a puppeteer and his strip show) that lead him to ‘Honest’ John Foulfellow and the Coachman. On the surface of things, the Coachman appears to be your typical vile trafficker of young children. Using Honest John’s talent for leading young boys astra... |
A closer look at the Coachman’s gambit, however, reveals a fatally flawed enterprise from a monetary perspective. The end product of what could be the then-Eighth Wonder of the World is the wholesale distribution of donkeys. You don’t have to be an economist to realize the futility in ever turning a profit with such an... |
The venture’s origin can be traced to a meeting at the local pub between the Coachman and Honest John. Promising Honest John ‘some real money’, the Coachman plops an enormous bag on gold on the table. Honest John manages to lure a few dozen boys to an undisclosed location. The dollar amount of that bag of gold cannot b... |
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