Post on 10-Apr-2018
CLINICAL TRIAL MANAGEMENT BOOT CAMP Taryn Losch-Beridon and Maureen Cleaver Sucampo Pharma Americas, LLC
The information presented and discussed represents the opinions of the author/presenter and, although descriptive of general activities, do not necessarily reflect the views of Sucampo Pharma Americas, LLC
Disclaimer
Importance of Site Selection and Project Success Investigative site payments and patient costs generally
comprise 20-25% of a given clinical project budget Cost of identifying, qualifying, contracting, obtaining IRB
approval for site, as well as issuance of upfront non-refundable payments and investigator meeting attendance, can exceed $20,000 dollars to achieve just one SIV-ready site This investment, on a study of 100 clinical sites where 30% of
sites do not perform, could amount to over $600K wasted
Investigative sites impact data quality, enrollment timelines, and overall study budget more so than any other study-related expense
Planning for Site Identification
Create a process and plan for Site ID Process commences with initial site search and outreach and
ends with establishment of final list of qualified sites
Consider utilizing in-house site ID team who will later become point of contact for sites and field monitors
Consider planned sources of clinical sites, e.g., CenterWatch, scientific meetings and congresses, ClinicalTrials.gov, literature searches, referrals from KOLs
Planning for Site Identification (cont’d)
Define the types of sites are you seeking Consider the patients seeking for treatment and the types of
treating physicians for condition, i.e., PCP or specialist…in some cases, multiple specialist types may be viable
Who are high prescribers in this therapeutic area, i.e., what does market research tell us?
Include assumptions for ratio of academic/VA hospitals to private practice or clinical research specialty clinics If these assumptions change during feasibility, may need to
adjust budget and/or timeline assumptions to account for more local vs central IRBs, longer contracting timeframes, and lower enrollment rates
Site ID Plan Content
Named team member roles and responsibilities Document process so all team members, as well as stakeholders reviewing plan,
can understand the process in detail. Pre-feasibility/feasibility questions CDAs and process for establishing
Consider at what point during site ID process protocol synopses will be shared Tracking tools for process activities Goal dates/timelines for each stage of process culminating with final Site
ID list Documentation of each stage of Site ID and review/decision-making for
site funnel Timeline for conduct of SQVs Target site locations, including countries
During site ID process, maintain map of potential sites to ensure wide distribution of site locations and avoid overlap in certain areas within a country/region
List of relevant SOPs
Advantages to Comprehensive Feasibility Validate protocol enrollment potential Refine forecasts of trial enrollment, costs, and timing Obtain practical, early feedback on trial design Establish rapport with site staff early to begin building
partnership Involve sites in protocol, eClinical System, site manual
development, etc. Sites are more engaged during study implementation when
their opinions are considered during study start-up Take the opportunity to listen to and respond to site needs
on an individual basis
Trial/Site Feasibility
Earliest possible opportunity to assess site quality before a large financial investment
It is not just a questionnaire and does not substitute for site qualification visit
Telephonic feasibility interviews vs. paper questionnaires Greater ability to gauge site enthusiasm, organization, staff
involvement … all drivers for site success in enrollment Allows for immediate clarification of unclear responses
unlike written responses to mailed questionnaires
Content of Feasibility Interviews
Investigator interest and capability Appropriateness of protocol requirements
Specifically ask PI and coordinator to comment on list of procedures and protocol visit schedule
Regulatory considerations and assessment of operational capacity of site (i.e., resources, processes)
Success (or failure) on similar studies previously and contributing factors
Determine how the site typically identifies potential patients and discuss the types of recruitment efforts may work best based on what has worked in the past If site asks a lot of questions regarding provision of budget for
recruitment/advertising, it may be a sign that site does not have adequate access to patient population for protocol
Site Qualification
Prior to an on-site qualification visit, ensure that the proposed investigators have been checked against applicable local debarment lists
Consider whether use of research naïve sites/PIs will be allowed and include a plan for additional training and oversight in the clinical monitoring plan
Maintain thorough documentation regarding site selection or reasons for non-selection
Waivers of qualification should only granted in unique circumstances such as current or recent participation in a Company-sponsored trial (e.g., within past 6 months)
If PI is replaced, must re-qualify
Other Recommendations for Success
Ensure clear lines of communication for site Always inform sites proactively regarding delays Consider one point of contact for contract negotiation and
another for budget negotiation For good sites who you want on your “team”, be
flexible For example, may not be able to offer payment more
frequently than quarterly, but can increase upfront subject payment that will be earned back as patients are screened/enrolled
Minimize site burden in setup of eClinical systems; ensure simplicity and organization of site tools and documents; streamline supply request and re-supply processes
…and a Few More
Maintain list of issues raised during feasibility for medical and clinical development team to consider before protocol finalization
Generate and maintain FAQ list amongst feasibility and clinical project mgmt teams, refining throughout site ID process
Don’t be afraid to label sites as back-up or decline for participation on a particular program….hitting target number of ID’ed sites means nothing if 30% or more of them underperform or don’t perform at all, wasting investment of precious time and resources to get them up and running
Outsourcing Drivers
Pharma/biotech increasing R&D budgets to “tap” into additional product pipeline, leading to increased reliance on CROs1
Increased regulatory, political, and scientific scrutiny on both investigational and marketed products
Generic product encroachment on market share and revenue Outsourcing solutions offering lower costs, better use of
internal/external resources, and high quality results are desired Smaller pharma/biotech do not have infrastructure to conduct a
full development program from nonclinical to marketing approval
1 Moody’s Global Corporate Finance, August 2008
Decision to Outsource
Why should a Sponsor outsource activities to a CRO Define strategy
Benefits of strong outsourcing partnership Supplement expertise of Sponsor, especially in new
therapeutic areas Resourcing flexibility / managing internal resources Utilize industry best practices
Assessing CRO Fit
Identify CRO(s) to partner with Conduct RFI (Request for Information) Provide general strategy Obtain general CRO capabilities and pricing
Conduct RFI meetings Identify which CRO(s) align best with company strategy
o Do therapeutic areas / strengths of CRO align o CRO strengths supplement Sponsor needs
CRO Evaluation
Request for Proposal (RFP) Provide template to prospective CROs, including as much
detail on study as possible Provide budget template if possible in order to assist in
comparing proposals Provide point of contact at Sponsor
o As questions are asked regarding RFP, provide responses to all CROs
Workshop Exercise Background
You are a Clinical Project Manager at, CBI Pharmaceuticals, a small sized pharmaceutical company. In October 2014 you are assigned a phase 2/3 study to manage. The protocol has been fully developed and is handed over to you in a final version. The company has set a goal of FPFV in March 2015. As a small sized company you do not have the internal resources to manage the study. You will need to fully outsource the study to a CRO. A list of potential CROs has been provided to you and the next thing you need to do is to send out RFPs.
Considerations when Outsourcing Site Selection Caution against blanket acceptance of CRO-suggested sites and
against waiving qualification for sites used by CROs recently Often CROs have sites they’ve used on different studies and have
established working relationships but NOT with the population you are studying.
What a CRO considers a good site (high speed enrollment) may be negligible in terms of quality.
CROs may recommend countries that are not feasible from a regulatory or patient population perspective simply because they have operational presence there
Budget negotiation by CROs on Sponsor behalf can result in higher investigative costs (~10% on average)
Sponsor is ultimately responsible for ensuring use of quality sites…you cannot outsource oversight of selection of qualified sites/investigators!
Site Contracting
Consider negotiation of master clinical service agreements for multiple studies at a single center
Document/understand relationships between study staff and clinical research unit Beware in contracting private research entities…ensure that
proposed PI is full-fledged site employee and the site can be held accountable for his/her performance on trial
Make certain to have strong language regarding PI replacement, notification thereof, and transfer of obligations/training
Include provisions regarding maintenance of documentation
Site Payment Details
Type Criteria for Payment Payment Details
Start Up Contract execution Start-up fees
Monthly Payments Per completed subject visits and screen failures, based upon site's entry of data on all required eCRF screens for each completed visit at the time of month close
Total visit costs for enrolled patients and/or fees for each screen failure less 10% holdback
Final Payment Issued upon database lock, return of unused study materials, and receipt of copies of site's notification to IRB regarding study completion/termination
Payment for remaining subject visits and screen failures 10% holdback payment Archiving fee Close Out
Ad-Hoc & Other Contracted Fees
Invoice from site required Payment for IND safety reports, SAE processing, Reconsenting
Site Budget and Payment Summary
Accept increased subject/visit fees over other contracted fees such as start up
Where possible include “per subject fees” within grid
Keep sites within the standard budget template If paying by procedure avoid site specific line items
within visit schedule Avoid accepting changes to payment terms Require invoicing for items outside of standard
template and terms
Selecting CRO for Study / Evaluating RFPs
Review all proposals and budgets Address any discrepancies / clarify differences Conduct face to face bid defense meetings
Provide agenda and list of attendees Provide CRO opportunity to discuss their approach to
conduct study Provides study team members to meet proposed
counterparts and ensure team cohesion
CRO Selection
Determine rating system What is most important? Therapeutic expertise, global
expertise, resourcing
Decision made on considering all factors (i.e. not choosing CRO based solely on price)
Master Services Agreement
Establish framework for relationship – preferred provider / general MSA
Govern legal and business terms Negotiate all legal terms Includes operational expectations
Scope of Work Define study specific details Delegation of responsibilities Transfer of Obligations Payment terms Timeline expectations
Study Oversight
Establish expectations upfront Conduct kick off meeting with CRO and Sponsor teams Review study details, changes since RFP Define communication plan, including escalation Define roles and responsibilities – utilize detailed RACI
Ongoing Study Management
Set standard meeting schedule Weekly? Telecons? Face to Face?
Periodic milestone reviews Identify when timelines are in jeopardy
Proactively address issues
Factors for a Successful Partnership
Trust is the foundation! Pairing of sponsors and vendors who are in
alignment on objectives and have a strong commitment to a successful outcome
Build effective lines of communication Put governance committees and executive oversight
mechanisms in place Ensure sufficient resources on both sides to
effectively collaborate and manage the relationship
Factors for a Successful Partnership (cont’d)
Early discussion of shared vision for relationship, goals, etc.
Open dialogue to ensure assumptions are valid and agreed upon amongst stakeholders
Common understanding of communication channels and expectations for reporting/monitoring of progress to upper management in both organizations
Factors for a Successful Partnership (cont’d) Ensure that teams mesh well; if foundation is not
sound, relationship will likely falter and goals will not be achieved Match experience levels; step in if major turnover
occurs on either side of relationship Develop issue escalation and contingency plans Conduct regular business performance evaluations
(two-way) Ensure roles and responsibilities are clearly defined
(e.g., detailed RACI charts)
Contact us
Maureen Cleaver
Director, Clinical Operations
Sucampo Pharma Americas
4520 East-West Hwy, Ste 300
Bethesda, MD 20814
mcleaver@sucampo.com
240-223-3618
Taryn Losch-Beridon
VP, Clinical Development
Sucampo Pharma Americas
4520 East-West Hwy, Ste 300
Bethesda, MD 20814
tberidon@sucampo.com
240-223-3604