A case study on how applied Six Sigma principles led to increased efficiency and overall improvement in decreasing cycle-time in Protocol Development and Clinical Study Start-Up.

1. George Betts, MBA, CPM
Head of Medical Affairs Operations
IPSEN
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2. Views and comments provided from this presentation
are solely of the presenter and do not in anyway
represent the views and/or comments of Ipsen.
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3. } As the Clinical Development stage is the most expensive phase of bringing a new
drug to market, nearly every pharmaceutical company over the past decade has
placed much emphasis on finding new ways to increase productivity and process
improving.
} This case study begins with an overview of the company’s pressing need to
identify areas to drive productivity and reduce costs in the Clinical Development
organization.
} Utilizing the DMAIC principle of Six Sigma (Define, Measure, Analyze, Improve,
and Control), the case study walks through the steps highlighting the challenges
and achievements along the way.
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4. } Rising costs to develop new drugs
} Challenges in meeting enrollment goals in
clinical trials
} Lost future revenues for delays in clinical
development
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5. } A cross-functional team was assembled to
evaluate ways to accelerate timelines in
clinical development trials
} Careful consideration was taken to include
the right key stakeholders on the core team
} Frequent communication throughout the
development of the initiative was essential
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6. Define
Measure
AnalyzeImprove
Control
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7. } The “D” (Define) in the DMAIC process focuses on
selecting high-impact areas to focus on
} Very important to have the team collectively define the
problem
} What may be perceived as the easiest step, can be a
challenge
} A key deliverable in the Define phase is a team charter
Define
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8. Problem Statement:
Delays in clinical trial execution result in delays to bring
promising new medicines to patients in need, increased
costs to bringing new drugs to market which translate to
higher prescription prices.
Scope:
US Clinical Development and US Clinical Operations.
This initiative will focus on the critical path activities of
clinical trial operations examining every step from
protocol development to FPFV
Areas of Focus:
• Protocol Development
• Site identification
• Contracting cycle-time
• Delays in trial launch (FPFV)
Approach:
• Utilize Six Sigma principles: DMAIC Define, Measure,
Analyze, Improve, Control
• Conduct further interviews with key stakeholders to
further define needs and validate proposed solutions
Core Team Members:
• Name - Name
• Name - Name
• Name - Name
• Name - Name
• Name - Name
Key Metrics to Measure Success:
• +15% improvement in protocol development cycle-
time
• +15% improvement in SSU cycle-time
• -15% reduction in number of non-enrolling centers
Timelines:
• Conduct kick-off mtg and define and align team
on objectives
• Analyze off-site feedback and Identify potential
work streams
• For further review with the CDMA Leadership team
• Produce recommendations and share with CDMA
Leadership
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9. } The “M” (Measure) in the DMAIC is about
documenting the current process, validating how it
is measured, and assessing baseline performance.
} We utilized tools in this phase which include trend
charts, fishbone diagram, critical path method
process flowcharts, and stick diagrams,
} It’s critical to measure the “right things” and to
establish acceptable baselines
◦ By creating a “critical path” process chart, the team can focus
in on what steps are important that if delayed, will extend the
entire project.
◦ Establish baselines such as:
– Step A à to à Step B should take at most 2 weeks to complete
Measure
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10. } The “A” (Analyze) in the DMAIC is when the team
isolates the top causes behind the metric being
investigated.
} It can be the most time-consuming phase.
} Can lead right into identifying the possible solutions
(Improve stage) and often can be done together
} We utilized the fishbone diagram tool – Was most
valuable
Analyze
Problem
Causes
Causes
Fishbone Diagram
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11. } A.K.A. Cause and Effect
diagram
} Very useful in opening up
dialogue among cross-
functional team members
} Was most effective to
identify where the root
problems were
Problem
Causes
Causes
Fishbone Diagram
Analyze
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12. Getting study
sites up and
running during
start-up takes
too long (avg =
19 weeks)
Contracts take too long to
negotiate
Fishbone Diagram
Purchase new external
FMV tool (PICAS)
Create new Contract Manager Role
CRAs and Study Mgrs. too busy
during SSU with other priorities
No organized internal or
external benchmarks used
for assessing FMV
Study Managers/CRAs not
experienced to negotiate
contract language
Initial legal review
takes >3weeks avg.
Legal staff under
reasourced
80% of sites demand
more compensation
than offered
CRAs not
empowered to
negotiate
Develop pre-approved back-up language.
Free us Study Mgrs/CRAs by
centralizing the SSU activities.
Establish master agreements with repeat centers
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13. Protocol
Development,
Site Selection
and SSU can
be improved
Fishbone Diagram
Studies often have a high % of
non-enrolling sites
Country feasibility
assessments not
done consistently
Too often the protocols
change significantly after
sites are selected
Wrong sites are
selected
Redesign Country
Feasibility Process
Change Site Selection SOP to
have process start AFTER
final protocol is produced
Site selection done
too early (prior to
final protocol)
Lack of training and
awareness on
importance of country
feasibility assessments
Contracts take too long to
negotiate
Purchase new external
FMV tool (PICAS)
Create new Contract Manager Role
CRAs and Study Mgrs. too busy
during SSU with other priorities
No organized internal or
external benchmarks used
for assessing FMV
Study Managers/CRAs not
experienced to negotiate
contract language
Initial legal review
takes >3weeks avg.
Legal staff under
reasourced
80% of sites demand
more compensation
than offered
CRAs not
empowered to
negotiate
Develop pre-approved back-up language.
Free us Study Mgrs/CRAs by
centralizing the SSU activities.
Establish master agreements with repeat centers
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14. } The “I” (Improve) in the DMAIC is when the team
focuses on fully understanding the top causes
identified in the Analyze phase,
◦ with the intent of either controlling or eliminating those causes
to achieve improved performance.
} The overall theme for the Improve phase is process
redesign
} Can often be done at the time the team is in the
Analyze phase
Improve
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15. } The “C” (Control) in the DMAIC is how the organization
sets up controls and monitors the effects of the
changes made in the Improve phase to guarantee
lasting results.
} Often there are process settings, setup procedures, etc.,
that require employees to follow specific requirements
in daily operations
– these items are typically documented in a control plan.
– In cases like this the Six Sigma team should do everything possible to
error-proof the process, and should then add the appropriate checks and
balances to the quality system for the long run
} Develop a scorecard that includes the key metrics the
team defined and have regular reviews with respective
leadership
Control
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16. Q1 Q2 Q3 Q4
%
of
non-­‐enrolling
sites <
15% 22% 20% 18% 16%
Median
Contracting
Cycle-­‐Time
(Local
IRB
sites)
<
14
weeks 19
weeks 18
weeks 12
weeks 12
weeks
Median
Contracting
Cycle-­‐Time
(Central
IRB
sites)
<
5
weeks 8.5
weeks 6
weeks 4.5
weeks 4.3
weeks
Median
Total
SSU
cycle-­‐time
(protocol
finalized
to
FPFV)
<
10
weeks 14.5
weeks 11.5
weeks 10.5
weeks 10.5
weeks
%
of
Total
Sites
Identified/Confirmed
by
+2
weeks
after
Final
Protocol
>
90% 50% 82% 89% 92%
Actual
Target
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17. } Encourage a Six Sigma Mind-Set within your
organizations
◦ Eliminate the thinking that, “it’s always been done this way”.
◦ Company leaders are continually looking to streamline operations and
improve processes
} When starting a process improvement effort, ensure you get
buy-in (sponsorship) from all relevant stakeholders within
your organization
} Throughout the process, provide continual updates to
sponsors
} Carefully define your problem statement and project
charter in the beginning with input from the team
involved.
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