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Based on Lendrem DW, Lendrem BC 2013 Torching the Haystack, Drug Discovery Today, 2013
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TORCHING THE HAYSTACKModels of Drug Development
Dennis Lendrem
Torching the Haystack
•1990• Business Process Reengineering prompted a
reinvention of pharmaceutical development processes. • Minimizing time to market identified as the key to
improving R&D productivity.• By placing development tasks in parallel, wherever
possible, we minimize time to market for successful molecules.
Torching the Haystack
Before Development Speed Initiative
6321 4 5
3
2
1 64
5
After Development Speed Initiative
Time to Market
Torching the Haystack
BUT
Torching the Haystack
MOST …molecules don’t make it to market
10%
Torching the Haystack
• We optimized the R&D process around an event which happens less than 10% of the time.
Torching the Haystack• By placing tasks in parallel to reduce cycle time we
inadvertently:• Increased R&D costs• Increased late-stage attrition rates, and• Increased expected time to market
Lendrem DW, Lendrem BC Torching the Haystack: Modelling fast-fail strategies in drug development. Drug Discov Today. 2013 Apr;18(7-8):331-6. http://dx.doi.org/10.1016/j.drudis.2012.11.011
p
1 - p
β
1
1-β1
1-α1
α
1
β
2
1-β2
C 2
C 2
C 2
C 2
C 0
C 1
C 1
C 0
C 1
C 1
1-αi
αi C i
C i
C i
C i
β
i
1-βi
1-α2
α
2
Stage i=0 Stage i=1 Stage i=2.... ...Stage i=m
.......
.......
a
b
c
d
• Example
Torching the Haystack
Time
New 2 2 2 + 2 = 4
Old 1 5 1 + 5 = 6
Lendrem DW More haste, less development speed. Scrip Magazine. Dec 1995, 22-23.
• Example
If p=0.10 then the average number of drugs tested before the first success = 1/p = 10
So the average time to launch the first drug:
= (10 x 1) + 5 = 15 years
= (10 x 2) + 2 = 22 years
Torching the Haystack
New
Old
New 2 2 2 + 2 = 4
Old 1 5 1 + 5 = 6
Lendrem DW More haste, less development speed. Scrip Magazine. Dec 1995, 22-23.
Torching the Haystack
• Conclusion?• For high risk projects, the expected time to market is
actually SHORTER for the serial process EVEN THOUGH THE CYCLE TIME is LONGER.
• This is the Development Speed Paradox
Lendrem DW, Lendrem BC The Development Speed Paradox: Can increasing development speed reduce R&D productivity? Drug Discov Today. 2014 http://dx.doi.org/10.1016/j.drudis.2013.09.002
The faster you go the longer it takes.
# screened = 38# discovered = 3# launched = 3
# screened = 58# discovered = 5# launched = 4
10
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10
20
30
1
2
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Cycle Time = 2+2 = 4 yrs Cycle Time = 1+5 = 6 yrs
Years
The Tetris Model
Torching the Haystack• By placing tasks in parallel to reduce cycle time we
inadvertently:• Increased R&D costs• Increased late-stage attrition rates• Increased expected time to market
• As a result, the industry became really slick at delivering late-stage failures to the market place, precipitating the current R&D productivity crisis.
Lendrem DW, Lendrem BC Torching the Haystack: Modelling fast-fail strategies in drug development. Drug Discov Today. 2013 Apr;18(7-8):331-6. http://dx.doi.org/10.1016/j.drudis.2012.11.011
Torching the Haystack
• The M25 Effect• Reducing Development Speed may actually increase
R&D throughput. • After London’s major orbital motorway where speed
limits were first reduced in the UK in order to increase traffic throughput.
Lendrem DW, Lendrem BC The Development Speed Paradox: Can increasing development speed reduce R&D productivity? Drug Discov Today. 2014 http://dx.doi.org/10.1016/j.drudis.2013.09.002
Torching the Haystack
Looking for a needle in a haystack?• Get the science right. Build opportunities to kill
molecules earlier in the development cycle.
• Assays that prevent molecules from entering the development process.
• Assays that allow elimination of molecules early in the development process.
Torching the Haystack
• Thanks• Richard Peck (Lilly)• Fred Snikeris (Quintiles)• Stephen Senn (CRP-Sante)• Clare Lendrem (NCL)• Frank Bonner (NCL)• Wan-Fai Ng (NCL)• John Isaacs (NCL)• MRG