Impacting Recruitment from a Sponsor / CRO Perspective

Society of Clinical Research Associates (SoCRA) Global Conference October 2016

Fraser Gibson HBsc. CCRP CCRC CCRAPresident

Advantage Clinical

Learning Objectives• Recognize the problem and impact of below expected patient

recruitment• Analyze the root causes of slow patient recruitment from a study and

site perspective• Discuss how sponsors can impact recruitment on a study and site

level

Contents• Problem Recognition; Patient Recruitment• Site and Study recruitment challenges• Sponsor and Site Responsibilities• Impacting Recruitment before enrollment• Patient Recruitment Specialist Role• Impacting Recruitment- SIV and Beyond• Case Study• Conclusion and Questions

Patient Recruitment- Current State• Sluggish patient recruitment is costing the clinical research industry

hundreds of millions of dollars. • These costs come from overruns of clinical trial timelines as well as

missed opportunity costs.• $500,000 / day for mid-range therapeutics• Upwards of $1 Million per day for blockbuster therapeutics

• Non-monetary costs to patients as effective therapeutics are delayed en route to market

Patient Recruitment- Current State• The majority of studies do reach their recruitment goals (# patients)

though the timelines to study completion can be doubled• 80+% of trials do not meet recruitment timelines• 11% of sites fail to enroll a single patient• 37% of sites under enroll• 90% of delays in trial completion are due to sluggish patient

recruitment

• TUFTS-CSDD 2013

Study Level Recruitment Challenges

Sponsor &CRO Responsibilities

• “Molecule to Market”- Streamline therapeutics to patients in clinics• Sound scientific design of protocol to answer medical / scientific

question• Human subject protection• Provide resources and support to implement trial at clinical sites

Site Responsibilities• Facilitate local trial conduct• Human Subjects Protection• Patient identification and enrollment• Conduct the study per approved protocol• Provide medical care to trial subjects• Submission of reflective / useful clinical data

Working Together• Common Goal: Get effective therapeutics to market• Current state of the relationship between sponsors and sites is more

transactional than collaborative in essence*

• Fostering collaboration between the clinical site and the sponsor / CRO will lead to increased efficiency and shortened trial timelines

“Coming together is a beginning, keeping together is progress,Working together is success”- Henry Ford

Impacting Patient RecruitmentBefore Enrollment

Study Protocol- Quality by Design• Global protocol complexity is increasing• Not all data collected is needed for safety and efficacy exploratory

• # of Inclusion / Exclusion per protocol is skyrocketing• Strike a balance between more open criteria while obtaining the population

you NEED

• Gap between those who write the protocols and those who are tasked with implementing them clinically

Study Protocol- Quality by Design• Protocol feasibility must be evaluated in the “real world” before

finalizing• Talk to your sites

• Logistics of patient identification / screening• Logistics of running the study per protocol (clinical feasibility)• Utility of inclusion / exclusion thresholds

• Talk to your patients• Evaluate patient databases

• Do these patients exist as we have defined them?• Can we loosen criteria while maintaining scientific integrity?

Site Selection• Recruitment success starts by selecting the right site• Clinical Resources• Staff- WORKLOAD• Patient Population• PI Involvement• Competing Studies

• Quality over QuantityLasagnas Law: The incidence of patient availability sharply decreases

when a clinical trial begins and returns to it’s original levels as soon as the trial is completed

Adding more sites• $20,000-$30,000 per site• 3-6 Month turnaround for budgets and contracts• Regulatory RestrictionsHOWEVER• Fresh pool of patients• New sites are more enthusiastic

Study Tools and Aides• Provide effective and useful study tools• Worksheets

• Pre-screen• Safety• etc

• Visit Calculators

• Goal is to make recruitment and trial conduct as easy as possible for the site

Recruitment Plan• Not just a document to be filed away• Dynamic- it will change as the trial progresses • Plan for recruitment lags• Pivot plan and tactics as you learn how the trial unfolds in the real

world

“Failing to plan is planning to fail”- Benjamin Franklin

Patient Recruitment SpecialistThe key to your enrollment success

Patient Recruitment Specialist• Fairly new and emerging role in the industry• Primary role is to support clinical sites in implementing an effective

recruitment plan• Supports recruitment efforts of a number of sites• Assists in setting up logistics of complex trials at sites• Site and sponsor liaison• Site Motivation• Compiles and shares knowledge between sites

Patient Recruitment Specialist• Qualifications• Clinical Research Experience (i.e SC,CRA)• Indication Experience (i.e ICU Nursing Experience)• Communication and Public Speaking • Comprehensive Study & Therapeutic Knowledge• Soft skills- “People person”

Patient Recruitment Specialist• How does a Patient Recruitment Specialist Support Recruitment• Site Visits

• Pre-Screen and recruitment logistics• Awareness presentations• Site staff education• Training• Mock patient training

• Periodic site communication• Sponsor-CRA-Site Liaison• Global pre-screening and screening data analysis• Implement global or site specific recruitment programs

Impacting Patient RecruitmentSIV and Beyond

Investigator Meetings• Typically performed post study launch• Periodic intra-study meetings• Provide tips, tools and resources for immediate use• Showcase high enrollers• Limit “re-training” on study protocol, procedures• Product & Study updates• Focus groups and small group peer learning

• Shown to jump-start enrollment post IM• Cost ~$2000 pp + time commitment from site

SIV Recruitment Discussion• Thorough Incl / Excl review• Define target patient• Identify and explore patient pools• Outline and demonstrate sponsor assistance tools / programs• Identify recruitment challenges for previous trials at site• Informed Consent and Mock Patient Discussion

Leaky Pipe- Recruitment Funnel AnalogyUsed with Permission from Beth Harper- Clinical Performance Partners Inc.

Pre-Screen and Screening Data• Reliance on site staff entering data ( weekly, monthly)• Identify what the patient population being screened looks like• Where are we losing patients?

• Specific incl / excl criteria, consenting, enrollment timelines etc.

• Identify the leaks and evaluate solutions• Site support ( Financial, resources etc)• Training ( consenting, screening etc)• Protocol amendments

Pre-Screen Data Example

Pre-Screen Data Example

Protocol Amendments• Evaluate patient population encountered • Evaluate risks and benefits of opening up criteria• Costly and time consuming solution• Total costs can be above $1M for larger studies• Burden on sites

• May be necessary to meet enrollment targets• Opens up new pool of patients

Surveys and Focus Groups• SC, PI, CRA, Sponsor Staff• Web based or face-face ( IMs, recruitment specialist)• Low Cost• Recognizes critical stakeholders• May reveal challenges unbeknownst to Sponsor• Opportunity to share successful practices with other sites

Awareness Presentations• Great for larger sites / hospitals• Conducted by Patient Recruitment Specialist• Spreads awareness of study and IP at the site• IP updates and emerging research• Brings teams together• Motivates and re-invigorates study at site

Focusing your Efforts• Top 20% of sites will enroll half

of your subjects• Focus enrollment efforts on top

50% of sites• Dormant sites are notoriously

difficult to stimulate• Consider site closures

alongside opening new sites

And More…• Study Coordinator engagement• Principal Investigator engagement• Gamification• Newsletters and communications• CRA engagement• Reduce burden on sites ( RBM, process shifts)• Your ideas?

Case Study- Background• Large Phase 3 pivotal trial seeking regulatory approval• Critical Care setting • Interdisciplinary teams• Surrogate consent• Strict Incl / Excl• Limited patient population• Strict enrollment timelines• 24 hour intensive treatment

Case Study- Background• ~70 Sites in US/Canada• Sample Size ~ 500• Regional Hospitals Large Academic Medical Centers• Novel treatment and screening assay

Case Study- Recruitment Projections• Initially opened 20 sites with enrollment target for 3 years• Approx. 1 patient per site per month

• After 1 year only 13% of enrollment reached• Approx 0.3 patient per site per month

• DSMB recommended Protocol Amendment further limiting patient population• Slow enrollment continued until Year 3 with only 50% of enrollment

completed

Case Study- Recruitment Specialist• Created and trained a Patient Recruitment Specialist role• Visited all sites and evaluated challenges to recruitment• Resources• Logistics• Patient Population• Trial Fatigue / Motivation• Competing studies• Lack of study awareness• Team disconnect• And many more….

Case Study- Recruitment Specialist• Sponsor created several programs to tackle these common challenges

to recruitment• Patient Recruitment Specialist continued to re-visit sites to:• Customize screening and recruitment plans• Motivate and engage study teams• Host awareness-presentations• Bring interdisciplinary teams together Logistics• Liaise with sponsor for further support (consent translations, screening

stipends, protocol and team training etc…)

• Continued weekly telephone and email correspondence

Case Study- Investigator Meetings• Held 4 regional Investigator Meeting in Spring/ Summer 2015. • Half day workshops for investigators and site staff• Small group settings facilitated knowledge sharing• Sponsor and sites shared screening and recruitment tips• Provided IP updates and discussed emerging research Motivation• Hosted anonymous focus groups for site staff to discuss challenges,

motivators, and how we could improve

Case Study- Incentive Program• Projected enrollment at current rates to reach target in 15 months• Target completion date was set for 5 months• Our “Big Hairy Audacious Goal”

• Calculated total trial costs to complete enrollment in 15 months vs 5 months• Ex. $1,000,000 in 15 months vs. $700,000 in 5 months*

• The remainder of the two was slated to boost enrollment and site performance in order to reach our 5 month goal

* Scaled example

Case Study- Incentive Program• These funds were repurposed to create a contingent financial

incentive program for our sites. • Funds would be awarded to sites as increasing Unrestricted Research

Grants if the site:• Enrolled > 4 subjects• Enrolled > 8 subjects• Was a top 3 enroller

• The grants were only payable to sites if the trial was completed by the 5 month deadline

Case Study- Incentive Program• A portion of the funds were also used to provide screening stipends

for sites providing additional resources to increase screening• Evening and weekend screening• Additional SC hours

• Ethical and legal implications to the program were cleared with US / Canadian legal teams and local IRBs

Case Study- Outcomes• Recruitment Specialist role boosted recruitment for all sites by 300%

over 2 years• 0.3 pspm to 0.9 pspm

• Recruitment Specialist role revitalized over 80% of dormant sites• Contingent incentive program led to the study being completed by

the 5 month deadline. 10 Months ahead of projections. • Net $0 financial expenditure on the program

Questions?fraser@advantage-clinical.com

www.Advantage-Clinical.com