1. Site & Patient Recruitment in (Early Phase)
Rare Disease Studies
Kevin J. Anderson, MBA
Associate Director, Clinical Operations

2. 2
Agenda
• Challenges in rare diseases
• Key site recruitment assumptions
• In-house approaches to site identification
• Outsourced approaches to site identification
• Incorporating evidence-based methods into site recruitment
• Lessons learned in rare disease site recruitment
• Approaches to patient recruitment
• Lessons learned in patient recruitment
• Conclusions

3. The Prevalence of Rare Disease
3
rare diseases
7000
of people with rare
diseases are children2/3
people are affected
with a rare disease
1in
affected globally
25
350m
The Global Genes Project. RARE Facts and Statistics. http://globalgenes.org/rare-diseases-facts-statistics/ Accessed June 2015.
National Institutes of Health, National Human Genome Research Institute. Rare Diseases Day 2012. http://www.genome.gov/27547266/. Accessed June 2015.

4. 4
Challenges in Rare Disease Studies
• Little is known about these diseases:
○ Data on the disease prevalence and incidence may be unavailable,
making it difficult to determine an appropriate study size1
• Extremely difficult to find patients:
○ May be in volatile regions with complex requirements
• Treating physicians often don’t fit into specialty ‘buckets’, and it can
be difficult to identify the specialties
• Principal Investigators may be far from a patient’s location:
○ Travel logistics can be complex and difficult for patients and their
families
• Rare disease patients are an inherently vulnerable population:
○ The majority of rare diseases affect children, who are considered a
vulnerable population – need to ensure naïve sites are well trained1
Patient
1. Registries and Rare Diseases, Applied Clinical Trials, Richard Gliklich, MD, Michelle Leavy, 1 March 2011

5. 5
Challenges in Rare Disease Studies (cont.)
• Majority of PIs are KOLs
○ Can be expensive and difficult to work with
• Many PIs are inexperienced:
○ In NorthAmerica and Europe, PIs often think they are experienced but are
not
○ In ROW, most sites are inexperienced and only nominally familiar with
ICH/GCPs
• Data integrity can be challenging:
○ Given the small patient populations, every data point counts
○ Every error/misinterpretation confounds the data
• Key Performance Indicators can be very different from industry KPIs:
○ Little rare disease benchmarking data available
• Diagnosis may be complex, particularly in cases where there is no
definitive test – therefore, having the right sites is critical

6. 6
Key Site Recruitment Assumptions
countries10–15
patient travel
Considerable
vendor staffing
for small studies
All study costs will be
patients20–30
Travel vendor
need to support
high

7. 7
Key Site Recruitment Assumptions
• Costs will be very high for every study:
○ 50–75% of sites will not enroll any patients
○ Despite site projections, most sites will enroll no more than one
patient
• A wide net must be cast, with many countries involved:
○ 10–15 countries may be involved in a study with 20–30 patients
• Will require considerable vendor staffing for small studies:
○ Multiple regulatory and EC submissions occurring simultaneously
• Travel vendor needed to support patient travel:
○ Some patients will require cross-country or international travel for
every treatment – need sites that can accommodate this

8. 8
In-house Approaches to Site Identification
• Reach out globally within the company across therapeutic
areas to all country managers, Commercial, MSLs, Med.
Affairs MDs, COLs for recommendations
• Secure funding for major global feasibility studies:
○ May need to contact 500+ sites to identify 20–30 for participation
• Ensure any sites involved in appropriate registries are
included in feasibility
• Search Engine Optimization and Paid Search are critical –
these can drive sites to you
• Social Media Outreach to find potential sites

9. 9
Outsourced Approaches to Site Identification
• Run global feasibility, reaching out to hundreds of sites worldwide
• Reach out to Patient Advocacy Groups if applicable
• Contact organizations such as Patients Like Me, who can assist you
in bringing disparate groups together – can locate sites that see the
patients
• Medical Informatics – some vendors can locate sites based on
treatment patterns and insurance information
• Consider hiring a ClinicalTrial Educator or equivalent, who can:
○ Dedicate time to searching authoritative text articles/journal articles for
study authors
○ Find investigators from similar trials posted on ClinicalTrials.gov and other
public sources
○ Search through key medical associations (e.g. ASH/ASN/ACR) for speakers
and authors on related disease topics

10. 10
Incorporating Evidence-Based Methods
into Site Recruitment
• Utilize medical informatics data on treatment/insurance claim
patterns in determining appropriate sites
• Use outcomes data from key academic papers
• Leverage market research data on key prescribers for drugs in a
similar therapeutic area
• Use publically available information to identify sites with
successful enrollment in similar disease areas
• Utilize CRO/internal recommended sites with prior history of
successful enrollment

11. 11
Incorporating Evidence-Based Methods
into Site Recruitment (cont.)
• Challenge estimates provided by sites in global feasibility
• Use de-identified pre-screen logs:
○ Checklist of key inclusion/exclusion criteria to be met
• Send logs to sites in advance of Site SelectionVisit (SSV)
• Review potential patient profiles at SSV
• Ensure patient profiles are a key driver for site selection decision

12. 12
Lessons Learned in
Rare Disease Site Recruitment
• From the outset:
○ Run global feasibility
○ Include a ClinicalTrial Educator or equivalent
○ Develop a search engine optimization and social media outreach
plan
○ Reach out to Patient Advocacy groups
• Recruit sites from a large number of countries and be willing to work in
volatile regions or countries with complex requirements
• Utilize medical informatics data for site identification
• Use outcomes research in site selection
• Ensure you have at least 2 sites for every patient
• Require sites to show evidence of patient population prior to selecting

13. 13
Approaches to Patient Recruitment
• Study landing page with a 1-800 number
• Outreach to patient advocacy groups to promote study
• Search engine optimization:
○ Link landing page to Patient Advocacy webpages
○ Paid search
○ Banner ads on Healthgrades
○ Targeted banner ads on LinkedIn
• Send ‘Dear Doctor’ letters to MDs local to study sites
○ Purchase physician mailing list from major medical organization
• Create HCP- and patient-focused posters and brochures

14. 14
Approaches to Patient Recruitment (cont.)
• Employ a ClinicalTrial Educator1 to:
○ Educate the principal investigator and site staff in successful enrollment
techniques
○ Network with healthcare facilities/providers that may refer potential
study patients
○ Reduce screening loss of otherwise excluded patients from trials through
identification prior to initiation of other therapies
○ Share best practices in focus groups of study coordinators or
investigators
○ Offer creative solutions to recruitment barriers and provide suggestions
to the trial team for development of recruitment tools
1. Quintiles Clinical Trial Educator Proposal, 22 August 2014

15. 15
Lessons Learned in Patient Recruitment
• Employ a ClinicalTrial Educator prior to study kickoff meeting
• Build a study landing page at the time of protocol synopsis
• Develop a comprehensive social media plan from the start
• Involve Patient Advocacy groups from the start
• Reach out to physicians via ‘Dear Doctor’ letters using targeted
MD lists purchased from major medical organizations
• Consider building a study app to track recruitment efforts

16. 16
In Conclusion
• There are many challenges
• There are many current solutions
• There are rapidly evolving solutions for the future
• Engage in as many approaches to site/patient
recruitment as you can from the start
• We are all constantly learning in this arena
• It is important to share our knowledge so others
can succeed – our patients depend on it!