Case study on Six Sigma (2014 ExL Conference)

George Betts, MBA, CPM Head of Medical Affairs Operations

IPSEN

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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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}  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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}  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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}  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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Define

Measure

Analyze Improve

Control

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}  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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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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}  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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}  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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}  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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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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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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}  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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}  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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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%

ActualTarget

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}  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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