Site & Patient Recruitment in (Early Phase) Rare Disease Studies

Kevin J. Anderson, MBA

Associate Director, Clinical Operations

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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

The Prevalence of Rare Disease

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rare diseases 7000

of people with rare diseases are children 2/3

people are affected with a rare disease

1 in

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.

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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

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Challenges in Rare Disease Studies (cont.)

• Majority of PIs are KOLs

○ Can be expensive and difficult to work with

• Many PIs are inexperienced:

○ In North America 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

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Key Site Recruitment Assumptions

countries 10–15

patient travel

Considerable vendor staffing

for small studies

All study costs will be

patients 20–30 Travel vendor need to support

high

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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

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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

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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 Clinical Trial 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

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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

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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 Selection Visit (SSV)

• Review potential patient profiles at SSV

• Ensure patient profiles are a key driver for site selection decision

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Lessons Learned in Rare Disease Site Recruitment

• From the outset:

○ Run global feasibility

○ Include a Clinical Trial 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

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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

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Approaches to Patient Recruitment (cont.)

• Employ a Clinical Trial 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

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Lessons Learned in Patient Recruitment

• Employ a Clinical Trial 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

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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!