There are many areas to focus on when taking steps towards improving clinical trial operations. This presentation focuses on 4 areas: Patient Enrollment, Study Start-up, Monitoring, and Project Management.

1. Optimizing Clinical Operations
Recent Trends & Approaches
George Betts, MBA, CPM
Conference Presentation
August 1, 2011

2. Disclaimer
Disclaimer
• The views and opinions expressed in the following PowerPoint
slides are those of the individual presenter and should not be
attributed to Ipsen Biopharmaceuticals, Inc. and/or Novartis
Pharmaceuticals, Inc.
• These PowerPoint slides are the intellectual property of the
individual presenter.
Confidential Information - G Betts presentation to Niiki Pharma August 1, 2011 Slide 2

3. Confidential Information - G Betts conference presentation August 1, 2011 Slide 3
Today’s discussion
Reducing cycle-time
Minimizing costs
Optimizing resources
Increasing productivity
Patient enrollment
Study start-up
Study monitoring
Areas of focus: Expected outcomes:

4. Confidential Information - G Betts conference presentation August 1, 2011 Slide 4
Non-enrolling sites
• Many data sources indicate that approx 30% of all sites initiated into a study
fail to recruit a single patient
• This comes at a high cost. Cost to initiate a site ranges between $18-$22K
• Industry best practice has leading companies operating with 10% of sites (or
less) with zero enrollment.
• Disrupts study planning and there are further costs associated with
implementing corrective action – new sites and new countries
• In my experience from >100 trials in multiple indications;
– Sites that do not recruit a patient within 90 days of initiation, will on average fail to
deliver 72% of the time
– Sites that recruit within first 30 days of initiation are 90% likely to continue to recruit for
the whole study
• Low recruiting sites tend to have poorer quality data due to lack of familiarity
with protocol
• Often KOLs are added to trials without regard to whether they can recruit.

5. Confidential Information - G Betts conference presentation August 1, 2011 Slide 5
Recommendations:
Managing non-enrolling sites
• Depending on the particular study, an acceptable ‘wait’ time should be
identified up-front and detailed within the site agreements.
• Failure to recruit beyond that time should lead to early termination:
– If no recruitment after 4 weeks from initiation – contact/visit site to investigate reason
why, offer support/advise, put them in contact with a recruiting site to exchange ideas
– If no recruitment after 6 weeks – letter warning that failure will lead to early closure of
site
– If no recruitment after 8 weeks – Close site early.
– Make it clear at that point, that “the protocol is not right for you” and “this will not
influence future studies"
• Finalize site selection only after protocol is finalized (or near finalization)
• Pre-identify back-up sites that can be ready to go in a short time frame

6. Confidential Information - G Betts conference presentation August 1, 2011 Slide 6
Minimizing over-enrollment
• Ability to stop patient enrollment once target has been
reached can often be a challenge across all centers,
particularly in large trials (Phase III).
• Cost associated with over enrollment varies, depending
on cost per patient (CPP) established in the site
contracts. Oncology trials typically high CPP.
– Recommendations:
• Utilize IVRS to better ensure real-time view of enrollment
status – Link to CTMS systems for optimal real-time oversight
• Ensure site contracts contain competitive enrollment terms

7. Confidential Information - G Betts conference presentation August 1, 2011 Slide 7
Effect of non-F2F Investigator Meeting on
Recruitment
• Engagement and motivation of ALL site staff associated with study is key to
successful recruitment
• The complex nature of clinical trials requires sponsors & sites to stay in
frequent communication with each other.
• General view: moving away from traditional F2F investigator meeting
format may negatively impact investigator motivation and limit potential
networking and communication opportunities that will contribute to the over
all success of a study
– From a LEAN 6-sigma perspective, this may lead to ‘sub-optimization’ . An
improvement in one part of a process, having an overall negative impact to the final
deliverable
Recommendations:
• Some companies have taken the approach to downgrade some (or all) of
their investigator meetings (less expensive locations and accommodations)
• Consider combining the strengths of both F2F and webcast technology for
those delegates who can not attend and record for future reference and
later on add-on sites
F2F
Webcast

8. Confidential Information - G Betts conference presentation August 1, 2011 Slide 8
Accelerating Study Start-Up
 Delays in SSU ultimately compress the patient enrollment period,
thus threatening the overall trial timelines
 Leading culprits for delays in SSU are:
 Timely finalization of Protocol
 Generation of protocol amendments during the SSU period
 Use of non central IRB type sites (large acedemic medical centers)
 Ethics/IRB approvals
 Protracted contract negotiations (including Informed Consent language)
 Lack of adequate study coordinator resources at site
 Competing trials at site
 On average, major academic medical centers can take upwards of
>16 weeks to get up-and-running

9. Confidential Information - G Betts conference presentation August 1, 2011 Slide 9
Accelerating Study Start-Up
Recommendations:
 Conduct rigorous analysis of protocol feasibility in targeted regions
 Align contract negotiation activities with regulatory document
collection
 Identify and select sites that utilize central IRBs whenever feasible
 Develop Master Agreements (and/or library of previously negotiated
terms) with repeat and targeted sites
 This also includes Informed Consent language
 Incorporate a reimbursement mechanism to compensate sites for
meeting an accelerated study start-up timeline
 Consider utilizing eDocument exchange technology (e.g. Intralinks)

10. Confidential Information - G Betts conference presentation August 1, 2011 Slide 10
Optimizing site and patient engagement
 General Statement: The best and most motivated investigator/site in
the world will not recruit well if there is no buy-in from the patients
 Effectively using patient groups can lead to patients actively seeking
sites
 At the protocol design stage, patient groups can provide valuable in-
sights into how outcomes should be measured and what will motivate
(or demotivate) them to participate
 Common patient concerns being;
 Use of placebo group
 Withdraw of treatment at end of study
 Side effects/risk
 Time commitment
 Actual procedures required
 Travel/parking/meal costs
 If patient groups can endorse the potential treatment and are
involved at the design stage, then there is clear potential for better
recruitment

11. Confidential Information - G Betts conference presentation August 1, 2011 Slide 11
Optimizing site and patient engagement
 Common motivators for investigators are;
 Scientific interest (innovative science and treatment)
 Fair market value for the work performed
 Level of support being offered by sponsor (inc. training for site staff)
 Burden of work being placed upon them
 Better invoicing/payment process
 Easy to work with (single point of contact with sponsors)
 CRA should be able to quickly resolve issues
 CRA/site relationship critical – soft skill training for CRA’s
Recommendations:
 Conduct pre-investigator meetings (TCs or Webcasts) for a select list of
sites whose performance metrics indicate they have the potential to be a
high recruiter – special treatment will drive buy-in
 Focus more support for sites straight after initiation as identified as most
critical period
 Newsletters to site showing anonyms status of recruitment to try and
generate competition between the sites

12. Confidential Information - G Betts conference presentation August 1, 2011 Slide 12
Innovative technologies in clinical trials
 Texting services are being explored by some companies
 Used to remind patients to take medication, a reminder to fast, when their
next visit was scheduled for etc appeared to improve compliance and
reduce drop out
 Web-based tools to facilitate document exchange
 Monte Carlo simulations using tools like StudyOptimizertm from
Decision View
 Virtual Clinical Trials?
 In June, Pfizer announced it would pilot the first virtual clinical trial.
 Patients will be able to participate remotely without having to visit the trial
sites.
 This new process is aimed at addressing rising R&D costs
 The process also has the potential to speed up clinical development,
widen the available trial population, and improve compliance.
 It uses mobile phone and Web-based technology to collect safety and
efficacy data and is consistent with the FDA’s Clinical Trials
Transformation Initiative (CITI) to improve the quality and efficiency of
clinical studies.
 For more information, contact: Tomasz Sablinski, MD, Ph.D

13. Confidential Information - G Betts conference presentation August 1, 2011 Slide 13
Other trends a variety of companies are exploring
 Risk-Based Monitoring
 Reducing the frequency of traditional on-site monitoring visits by
incorporating remote access to electronic clinical systems.
 Should include a centralized, real-time overview of the data with risk
detection and mitigation strategies
 Potential Benefits:
 May lead to early identification of problems so that they can be remedied quickly, protecting
patients and preserving the overall
 Improves the efficiency of CRAs, as they concentrate on the sites that need help and allow
competent sites to proceed without unnecessary interference.
 Improves the reliability and verifiability of study data, avoiding unpleasant surprises upon
regulators’ review.
 Has the potential to reduce overall monitoring costs

14. Confidential Information - G Betts conference presentation August 1, 2011 Slide 14
Other trends a variety of companies are exploring
 Social media: A tool for clinical trial recruitment?
 Through online forums like Facebook, Twitter,
Patientslikeme.com and Foursquare, clinical trials can find
large, enthusiastic, and qualified groups of patients online.

15. BACK-UP SLIDES

16. Confidential Information - G Betts conference presentation August 1, 2011 Slide 16
Social media: A tool for clinical trial recruitment?
• PatientsLikeMe’s solution is called Clinical Trial Awareness.
• Pharma companies are allowed to send out a co-branded
email that informs a disease community (and qualified
patients therein) that they may be eligible for a clinical trial.
• PatientsLikeMe encourages companies to approach the
patients as partners rather than subjects—partners who
need to hear the benefits of enrolling.
• Patients, then, receive that e-mail and can directly sign up
if they like.
• More often than not, however, they take the clinical trial to
the forum to discuss with each other what it’s about, if the
benefits are justified, and why it may or may not be
worthwhile.