Charles Rathmann, Director, Recruitment Enhancement Core ICTS Regulatory Support Center

1. "The Recruitment Enhancement Core"Innovative Recruitment Strategies for Washington University School of Medicine Charles Rathmann, Director, Recruitment Enhancement Core ICTS Regulatory Support Center Washington University School of Medicine October 26th, 2010

3. Participant Enrollment A Global Problem… • 20% of sites are responsible for >50% of the subjects • 50% of sites enroll over 90% of all subjects (*Quintiles data) • Only 57% of investigators are from the US, and only 46% of industry sponsored study patient visits are in the US • 27% of US investigators fail to enroll any subjects - industry • 75% of US investigators fail to enroll target # of subjects - industry • Only 7% of sites actually deliver what they proposed in the feasibility assessment • 90% of all studies extend their enrollment period WHY? K. Getz, CIS, Tufts CSDD and R. Krall, KMR 2006 Data (15 Large Pharma Companies)

4. Participant Enrollment A Global Problem… • Recruitment is a multi-variable problem! • Recruitment is difficult! • As inc/exc criteria get more restrictive – more patients are needed to screen. • Protocol Feasibility is lacking! • Strategic Recruitment Planning isn’t done! • CRC’s are normally tasked with recruitment and are taxed with numerous other responsibilities! • Recognizing the “Recruitment Specialist” Role as a critical part of study execution (Recruitment is an after thought).

5. Participant Recruitment A Global Problem… • FDA conducted a survey with ACRP members. • 1024 completed the 28 question survey. • Majority of respondents were CRC’s (75%) and project managers (9%). • Majority of respondents worked at a Clinical Study site or in Academia (85% in an urban center). • Respondents were asked to select all applicable answers. E. Pinnow et al., “Identifying Obstacles and Opportunities to R & R in Clinical Research,” The Monitor, Aug 2010: 59-64.

6. Factors that Ease Recruitment A Recent Survey… • Study mentioned by doctor before recruiter speaks to the patient: 772 (76%) • Perceived benefit of the treatment for self: 770 (76%) • Monetary incentive to participate: 540 (53%) • Recruiter able to answer questions: 460 (45%) • Perceived benefit of the research for others: 425 (42%) E. Pinnow et al., “Identifying Obstacles and Opportunities to R & R in Clinical Research,” The Monitor, Aug 2010: 59-64.

7. Barriers to Recruitment A Recent Survey… • Finding eligible patients: 780 (77%) • Patient refusal due to time commitment: 547 (54%) • Patient refusal due to risk of intervention or new treatment: 475 (47%) • Patient refusal due to geographical or transportation constraints: 344 (34%) • Patient refusal due to preference for SOC: 343 (34%) • Competing protocols for same patient pop.: 294 (29%) E. Pinnow et al., “Identifying Obstacles and Opportunities to R & R in Clinical Research,” The Monitor, Aug 2010: 59-64.

8. Enrollment Enhancement Project (EEP) • Began in early 2006. • Identify root causes of WUSM enrollment problems and develop potential strategies for improvement. • A streamline & efficient enrollment process to: • Include thousands more participants into leading-edge trials by using a systematic & data-driven approach; • Support the answering of revolutionary research questions • Offset the labor costs involved in getting trials up and running; • Accelerate the clinical research process to bring useful treatments to patients.

9. Enrollment Enhancement Project (EEP) • In 2005, clinical trials at Washington University were enrolling at 60% goal on average (9/15) – numerous issues identified for this.*** • The EEP showed: By creating a more efficient enrollment process, this increased subject enrollment will help off-set the tremendous amount of labor & start-up costs incurred by the sites (and the sponsors) before the trials are up and running and during trial execution. • The Recruitment Enhancement Core (REC) was developed in late 2006 as a direct result of this EEP as well as the need for a Participant Recruitment Core (CTSA)

10. Enrollment Enhancement Project (EEP) • The REC focus was a systematic, data-driven and strategic approach in the clinical research environment – very metrics driven and customer oriented (corporate mindset in an academic setting). • Strategic Recruitment Plan Development and implementation. • REC Pilot was developed and implemented – 25 trials over 3 therapeutic areas - enrollment was at 125% for studies in the pilot after 12 months.

11. Participant Enrollment PILOT PROJECT METRICS (Enrollment and Randomization Update – Final Pilot Numbers)

12. The Recruitment Enhancement Core (REC) The Vision • The REC takes responsibility for enhancing recruitment by passing a steady stream of pre-screened participants to PIs and study coordinators for more predictable and timely enrollment. • The REC also provides assistance with creating targeted, comprehensive strategic plans for participant recruitment, which maximizes recruitment efforts for targeted clinical trials (which includes creative solutions to rejuvenate the execution of difficult-to-enroll trials)

13. The Recruitment Enhancement Core (REC) The Vision (cont.) The goal of the REC as a centralized resource, is to free up the time of study coordinators and PIs, so they can focus on consenting and enrolling participants, while we spend the time trying to get interested, pre-screened participants to the studies that they desire to be included in.

14. The Recruitment Enhancement Core (REC) • Recruitment Enhancement • Systematic, Data-driven and Proactive Approach • Strategic Planning and Implementation • Recruitment Services Menu – Levels of Service • Volunteer for Health (VFH) Office and Program • Space in South BJH Lobby • VFH Program is still focused on customer service • Research Participant Registry (RPR) powered by VFH • Database with Potential Participants • Queriable to specific inclusion and exclusion criteria

15. The Recruitment Enhancement Core (REC) Levels of Service – Support is cumulative • Level 1 • RPR Db query and referrals, Web registration and posting, Flyer creation for office, RPR Face Book Fan Page, Centerwatch.com listing, BJC Today Ad (recommended for all studies) • Level 2 • Media Development and Placement Support (print – free or paid, radio, TV, e-mail blasts, etc.), Medical Public Affairs involvement

16. The Recruitment Enhancement Core (REC) Levels of Service – Support is cumulative • Level 3 • Recruitment Consultation - Strategic Plan Development - Accountability (3 minimum avenues of recruitment per phase), Protocol Feasibility • Level 4 • Strategic Plan Implementation - Level of support , enrollment

17. Participant Recruitment Strategic Recruitment Planning Meeting • Development of Strategic Recruitment Plan. • Team consists of PI,CRC, and study staff as well as a REC Director and Recruitment Specialist. • 1 Hour session to identify study patient population, past recruitment methods, potential barriers and creative idea sharing (ad creation and placement ideas). • Discuss primary and secondary recruitment avenues to be utilized.

18. Participant Recruitment Strategic Recruitment Planning Meeting (cont.) • Identify KEY inclusion and exclusion criteria to query the Research Participant Registry(Over 12,000 queriable) • Discuss and develop pre-screening tools for Recruitment Specialists. • Submit and secure necessary IRB approvals for techniques and materials.* • Ideally, to occur before enrollment period officially begins.

19. The Recruitment Enhancement Core (REC) (For ICTS Reporting Purposes – REC impact)

20. Case Study 1 • MEAC – Metabolic Effects of Antipsychotics in Children (Dr. J. Newcomer) • Sponsor – National Institute of Mental Health (NIMH) • Enrollment Target – 240 (4 years of enrollment – Started June 2006 – linear need of 5 per month/15 a quarter) • Current Enrollment as of June 2010 – 233 • Enrollment percent to goal prior to REC involvement (June 2006 through January 2007) • 10 enrolled - Target of 40 = 25% enrollment percent to goal (not meeting enrollment %) • Enrollment percent to goal with REC involvement – (February 2007 through June 2010) • 223 enrolled – Target of 205 = 109% enrollment percent to goal (Level 3 then Level 4) • Overall - 233/240 = 97% of enrollment target • This grant is 6 million over 5 years – (500k criteria – 85% enrollment per quarter)

21. Case Study 1 • Key Recruitment Strategies: • REC support started as consultative and quickly went to the Level 4 – implementation of Plan, eventually securing a 20% FTE for recruitment on this trial. • Physician and Medical Provider network creation via call cycle and presentations (Pediatric Psychiatrists, Pediatric Neurologists, social workers, school district nurses and counselors, presentations to pediatrician groups individually and respective societies and strategic follow up with attendees and key targets.

22. Case Study 2 • TOGA – A Randomized, Sham-Controlled Trial to assess the safety and effectiveness of TransoralGastroplasty in the Treatment of Morbid Obesity (Dr. S. Jonnalagadda and Dr. C. Eagon) • Sponsor – Satiety, INC. • Enrollment Target – Contracted for 20, starting in July 2008 (competitive) • Final Enrollment and Randomization • 106 enrolled, 46 randomized

23. Case Study 2 • Key Recruitment Strategies: • VFH/RPR Database Queries and Human Nutrition Department Database Queries • Information Sessions for Pre-Screened potential Participants (had a hold list of over 100 for the majority of the trial). • Medical Public Affairs collaboration to secure numerous forms of FREE Media (TV news spots) – First procedure in the U.S. story helped to jump start. • Did not need Sponsor Advertising funds which allowed us to convert those funds to Recruitment Support Funds (Total REC Support - $10,000) • The TOGA trial, when complete, will generate over 1.2 million dollars of clinical trial revenue.

26. Case Study 3 • Phase 2, Randomized, Multicenter, Placebo-Controlled, Double-Blind Parallel-Group study to evaluate the efficacy, safety and pharmacokinetics of QD Oral E5501 tablets used up to 7 days in subjects with Chronic Liver Diseases and Thrombocytopenia prior to elective surgical or diagnostic procedures. • Sponsor – Eisai, Inc. • Enrollment Target – Contracted for 3, starting in December 2009 (10 weeks late) • Current Enrollment and Randomization as of 3/1/10 – 5 enrolled, 3 randomized - #4 of 25 sites in just over 2 months recruiting (12 sites had yet to enroll 1 patient!)

27. Case Study 3 • Key Recruitment Strategies: • Liver Transplant Lunch and Learn with coordinators and clinicians – weekly reminder e-mails about trial, which include Hepatology and GI. • Hepatology clinic medical record screening daily – back 1 year and future scheduled patients – PI and Sub I’s. • Hepatology new patient and procedure lists being reviewed, screened and followed for inclusion status in the trial daily (opportunity for enrollment can change). • Medical Informatics query of hospital db’s for patients with documented thrombocytopenia nightly (attached to an approved list of agreeable clinicians – patient contact is already approved) • BARRIER – geography – would have twice as many enrolled if potential participants were local.

28. Successful Strategies • Utilize the REC – if only for a consult – as well as the Research Participant Registry to see if we can help jump start recruitment – it is all we do! • Before agreeing to execute a trial, perform a Front-End Feasibility Analysis to see if the trial is feasible and funded appropriately. • Budget adequate? Potential population of participants available? Competing trials? Will you need outside support? Have a form that you can fill out as a guide – Have the REC involved with the Pre-Site visits to ask recruitment questions. • A focused, targeted recruitment specialist and strategic plan that is implemented and adjusted for return on investment can have a HUGE impact on clinical trial recruitment – a couple trials or a portfolio of trials. • Develop the plan early – be willing to review and update it for effectiveness – REC can help.

29. Successful Strategies • Clinic and/or Hospital Database queries to identify potential participants. • Could be from PI’s (specialty) clinic or target population clinic – HIPPA considerations • Takes time and resources (All Scripts screening). • ***Funding - Always ask for advertising and recruitment support funds in your budget process – for grants, this can be partial or full FTE support – for Industry, ask for a flat dollar amount as a line item (direct sources of revenue). • 20 -40% FTE on individual trial grants. • $5000/$5000 Recruitment and Advertising Support from Industry – this number will be increasing. • JIT Support from the ICTS – funded by CTSA - $5000/year/trial for REC support.

30. Successful Strategies • Have numerous avenues of recruitment going at once – waiting for the PI to identify patients may not always be the most efficient way to recruit. • Not all cost money – group info sessions, campus media and print, e-mail blasts to different groups, employee shuttles, clinic post cards, Medical Public Affairs collaboration, etc. • Collaboration with PI’s who do similar research – At Washington University or at other Academic Medical Centers on the protocol. • Seek out high enrolling sites for feedback • Be willing to set up monthly calls to collaborate, focused on recruitment • Experienced PI’s with targeted patient populations (media suggestions)

31. Institutional Opportunities • Utilize available institutional resources – • CTSA – should have a website – find the navigator! • You may have to do a little investigating! • Recruitment Cores – can have information about local resources that could be maximized. • Medical Informatics • Let you know what is possible – technology that can be utilized. • Medical Public Affairs (MPA) – get the word out! • Marketing the institution to the community. • Marketing Communications, Creative Services.

32. The Recruitment Enhancement Core (REC) • Where are we going: • Young investigator focus – “JIT” funds from ICTS • Supplement recruitment efforts not budgeted for • Strategic partnerships with Industry Sponsors and CRO’s • Trial Placement from Sponsors (Quintiles and INC Research) • Clinic and Hospital Db reviews – • Medical Informatics and All Scripts (feasibility) • FTE support from PI’s and study teams • Billable Rates for selected services

33. The Recruitment Enhancement Core (REC) • Where are we going (cont.): • Physician Referral networks – study by study • In the community or on campus • Research Match.org utilization • Challenging due to additional IRB requirements and the RPR. • NIH Low Enrolling Trial Support • RPR Database Upgrade • Retention Strategies and Surveys

34. The Recruitment Enhancement Core (REC) • Facilitates more predictable and timely recruitment and enrollment • Allows for hypotheses to be tested most completely and most efficiently • Provides for attractive site selection to external sponsors knowing that recruitment is a priority in the competitive landscape of trial placement or grant awarding

35. AcknowledgementSupported by theClinical and Translational Science Award (CTSA)program of theNational Center for Research Resources (NCRR)at the National Institutes of Health (NIH)Grant Numbers UL1 RR024992, KL2 RR024994, TL1 RR024995

36. The Recruitment Enhancement Core (REC) Any Questions? Contact Information: Charles Rathmann 362-0897 rathmannc@wusm.wustl.edu 362-1000 (VFH Office)