Optimizing Clinical Operations

Optimizing Clinical OperationsRecent Trends & Approaches

George Betts, MBA, CPM

Conference Presentation

August 1, 2011

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

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:


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.


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


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


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

F2FWebcast


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


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)


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


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


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


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


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.

BACK-UP SLIDES


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.

Healthcare

Optimizing Clinical Operations