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TORCHING THE HAYSTACK
Models of Drug Development
Dennis Lendrem

Torching the Haystack
•
• 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.

Before Development Speed Initiative
6321 4 5
3
2
1 64
5
After Development Speed Initiative
Time to Market

MOST
…molecules don’t make it to market
10%

• We optimized the R&D process around an event which
happens less than 10% of the time.

• 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
α
i 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
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
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.

• 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
20
30
40
50
10
20
30
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Cycle Time = 2+2 = 4 yrs Cycle Time = 1+5 = 6 yrs
Years
The Tetris Model

• 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

• 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

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.

• 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

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Pharmaceutical R&D: Looking for a Needle in a Haystack? Torch the Haystack.

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