Optimizing Clinical Operations

Recent Trends & Approaches

George Betts, MBA, CPM Conference Presentation August 1, 2011

Todays discussion
Areas of focus:
Patient enrollment

Expected outcomes:

Reducing cycle-time
Minimizing costs
Study start-up

Optimizing resources
Study monitoring

Increasing productivity
Confidential Information - G Betts conference presentation August 1, 2011

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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 never recruit a patient 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.
Confidential Information - G Betts conference presentation August 1, 2011

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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

Confidential Information - G Betts conference presentation August 1, 2011

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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

Confidential Information - G Betts conference presentation August 1, 2011

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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
Confidential Information - G Betts conference presentation August 1, 2011

Webcast F2F

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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

Confidential Information - G Betts conference presentation August 1, 2011

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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)
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Confidential Information - G Betts conference presentation August 1, 2011

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 insights 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

Confidential Information - G Betts conference presentation August 1, 2011

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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 CRAs

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

Confidential Information - G Betts conference presentation August 1, 2011

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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 FDAs Clinical Trials Transformation Initiative (CITI) to improve the quality and efficiency of clinical studies.

For more information, contact: Tomasz Sablinski, MD, Ph.D

Confidential Information - G Betts conference presentation August 1, 2011

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Other trends a variety of companies are exploring

Remote monitoring (knowledge-based monitoring)
Reducing the frequency of traditional on-site monitoring visits by incorporating remote access to electronic clinical systems.

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.

Confidential Information - G Betts conference presentation August 1, 2011

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BACK-UP SLIDES

Social media: A tool for clinical trial recruitment?

PatientsLikeMes 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 subjectspartners 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 its about, if the benefits are justified, and why it may or may not be worthwhile.

Confidential Information - G Betts conference presentation August 1, 2011

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