Outsourcing Clinical Trials Canada 15 th November 2012 Vendor Selection: Identifying Effective Procedures & Strategies John S Andrews PhD President and CSO, NeurAxon Inc President, Ketogen Inc CSO, Talon Pharmaceutical Services 1
Understand the Problem of Managing Needs and Expectations Confidential 2
Changing World Pharma restructuring and outsourcing clinical trials management VC s increasingly want virtual companies Expertise is moving Confidential 3
Vendor Selection Clinical Trial Strategy Clinical Research Organisations Checklist There isn t one checklist There is often more than one CRO involved in any study Confidential 4
Pre-RFP Who am I? What s a CRO? Confidential 5
What Type of Trial for What Purpose Safety First in man, follow-on or special populations Efficacy New mechanism or new population Type of Efficacy Trial Dose range finding Signalling Proof of principle Registration Sale Confidential 6
Know What You re Asking in a Trial Understand Company Responsibilities Trial design Classical or adaptive Positive controls Mission creep End point confusion Plan for success but prepare for problems Not in the checklist It s your study Confidential 7
Trial Components and Checklists Trial location Time allocated PI selection Regulatory Protocol Investigators Brochure Recruitment Advertising Data collection paper/electronic Site Monitoring Biochemical analysis PK IRB/ethics committees (central or individual) Packaging Distribution Site selection Site Costs Haematology Auditing Safety review Statistical analysis Data storage/security Reporting Confidential 8
What Type of Company What do you bring other than money Small staffed R&D company Scientific, Regulatory and Clinical Officers Virtual company Business officers only Multiple consultants Ownership, oversight and stewardship Agreement and understanding of the whole trial process and your role in it Meaningful approach to metrics Confidential 9
RFP to CRO s Submit a Protocol which Demonstrates an Understanding of the Whole Trial Process not just the Price Internal Protocol Regulatory Project management Joint Protocol finalisation Regulatory Contracted Packaging and distribution Trial and monitoring Statistical Analysis Sample analysis Storage Confidential 10
Diligence is Expected Confidential 11
CRO Review Selection of CRO Full Service Split Service Full Service CRO One stop shop: everything handled by one company Subcontracted and project managed Interview multiple CRO s after submitting protocol Detailed review of their response to study protocol Approach, projected time and cost etc Open and upfront on expectations and limitations Confidential 12
Know The CRO(s) Large vs Small Large Higher turnover more difficult to build a relationship A team or B team Priority Smaller Less turnover, may be easier to work with More involvement, success of every trial is more important Confidential 13
Know The CRO(s) Active in your therapeutic area How many trials, what type, when? Active in your jurisdiction How many trials, what type, when? Talk to previous clients Quality of sites, monitors and PI s Talk to PI s Quality of patients Failed trials Inactive drug Failed study Poor design? Patient quality? Timeliness number of on-time studies Confidential 14
Recruitment 70% of efficacy trials fail to recruit on time Projected recruitment rates vs actual Past trials in same therapeutic area Past trials in same jurisdiction Past trials in different TA/J Correction factors accounted for in bid and or budget Additional back-up sites prepared Use of adjunct patient gathering organisations Projected costs and final costs Pass-through costs Out of scope costs Confidential 15
Diligence in Depth Review of accreditation Personnel qualifications, job descriptions, organisation, training plans, staff turnover etc. Results of all previous regulatory inspections Data transfer processes and security Security of physical locations where services are provided (server rooms, file rooms, etc.) The number of sponsors or studies currently supported by the available staff Stability Financial well-being Confidential 16
Clarity of Communication Multiple face-to-face meetings should be undertaken before signing such that agreement is clear on all major issues namely:- That processes for both companies are described in detail (SOPs, training etc) The roles and responsibilities for sponsor and CRO(s) are defined Expectations of both teams with respect to deliverables, timelines and resources Communication and decision-making strategy Issue resolution process Budget planning and management What s in the price, what isn t Expectations and performance metrics Confidential 17
Personal contacts Develop the Partnership Human Touch All CRO s in the study Between CRO s in the study Regular meetings after initiation Updates, open discussion Managing expectations Future relationship planning Ideally it s a campaign not a trial Let them know they are important Sharing responsibilities and success Confidential 18
Summary How much do you need full turnkey operation, monitoring, IVRS, lab services etc., or just site management and monitoring The CRO should fit the therapeutic purpose- it helps if the CRO specialises in the area, or in specialty study designs, e.g., adaptive study designs The starting point for a CRO selection process must be the most complete protocol you can provide to them every assumption they provide will be driven by this including recruitment rates, budgets etc Be aware to what extent the CRO is virtual, geographic limitations and sub-contractors that you may need to be aware of and oversee Confidential 19
Summary Planning multiple cross-group issues e.g. An existing in-house database must be synchronised with the CRO databases and systems; If the database resident at another CRO, then the interface between must be managed If multiple small CRO s are involved it must be clear how you will manage the relationships and interactions of all the groups There is no substitute for bringing in several CRO s and making them present their bids to you, including their vision and plan for executing the study The checklists are an essential guide to diligence, negotiation and deal structure Communication and personal interaction are the key to developing a partnership for problem solving and success Confidential 20
Preparation & Teamwork = Successful Project Launch! Confidential 21
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Nitric Oxide (NO): A Brief History 17-18 th Century 19 th Century 20 th Century 21 st Century Identified and synthesised as a gas NO as a toxic gas Nitroglycerin explosive and causes headaches Nitroglycerin relieves angina Characterised as a major pollutant in smog EDRF guanylate cyclase and cgmp dependent NO can regulate cgmp via guanylate cyclase Cells make NO, NO=EDRF 1992 Molecule of the Year Science Magazine NO reliably induces migraine 1998 Nobel Prize for Physiology & Medicine Inhibiting NO reduces migraine Most studied endogenous transmitter of the decade Multiple NOS inhibitors enter clinical trials 23 Confidential 23