CBI - Clinical Trials Budgeting and Forecasting Central Lab Budgets CBI - Clinical Trials Budgeting and Forecasting February 9, 2016 Kelli Isaacs

Agenda Central Lab Budgets – What’s Required Moving from Proposal to Contract Hitting Kits on Site Date - Key Milestones Budget versus actuals and forecasting Best practices for including a central lab in your study Let attendees know that we are here to help. We do not intend for this to be a selling piece. This is meant to make all aware of process and expertise. With this additional understanding across the board, we can maximize efficiencies and therefore deliver results in the best way possible.

“ In the past 15 years, data produced by central laboratories has represented more than 60 per cent of all data submitted in a New Drug Application (NDA). This percentage is expected to approach 80 per cent within the next several years(1). “ ACM understands the impact that central lab has on your submission. The data collected during a clinical trial forms the basis of subsequent safety and efficacy analysis which in turn drive decision making on product development in the pharmaceutical industry. 1. Anyszek T, Hayashi E and Morrow F, Decentralising Central Laboratories, International Clinical Trials, August 2010

REAL QUOTES “The protocol is almost final; can we get kits on site this month?” “First Patient In is in 4 weeks” “Not much testing in here so we’re thinking you should be able to set up the study quickly” “It’s exactly like the last study” “Can you provide a proposal for a study with 50 sites and 100 patients” “I have everything in place, sites are set; I just need a central lab”

I. Building the Central Lab Budget – What’s Required Scope of Work parameters Timelines Regions involved Patient numbers Operating Assumptions Safety Testing only Analytical lab involved but need kits from central lab Cost Drivers Logistics TAT Time

Building the Central Lab Budget Proposal Checklist Patient Breakdown Specimen Storage Requirements Investigator Meeting Attendance Data Transfer Frequency Shipping Requirements Analytical Lab Information SIV (Kits on Site – per region) FPI (per region) LPLV Study Duration Database Lock Countries/Sites Breakdown The proposal checklist is a tool utilized by ACM. It contains the key information from the RFP which helps build an accurate proposal and budget. Key items include test requirements and key project timeline dates As much information that can be provided for each of the above areas will help build the most accurate, cost effective budget.

Proposal Checklist Specific Content Laboratory Testing Fees Specimen Storage Fees Kit Fees Project Setup Fees Investigator Meeting Fees Project Management Fees Data Transfer and Reporting Fees Estimated Transportation Fees ACM uses a standard budget template with the included parameters The more information, the better.

Building the Central Lab Budget Key Cost Drivers Transportation Real-time shipping Using speciality couriers Shipping estimates are blended rates based on courier/weight/stability as we typically do not have exact locations at the proposal stage Esoteric Testing Sensitivity of analytical methods (Qualitative vs. Quantitative) Viability of Samples TAT on results STAT vs real-time Others: Exclusion criteria Batch analysis vs real-time analysis??? But if endpoint for your study, and need .002 Qualitative –do you have diabetes or not to quantitative- level of glucose, micrograms per millimeter of glucose One of the things we try to get our clients to start at end. What are the outcomes you want, and we work back – what is the data you need. Start with the endpoint in mind.

II. Building the Central Lab Budget Moving from Proposal to Contract Final Budget Final Proposed Budget is the “best estimate” based on specifications provided. The amount billed for is based on Actuals: Test performed Specimens received for storage Kits sent Data Transfers Data Cleaning per requisition Shipments We recommend a study true-up at 20-30% of enrollment (speed of enrollment, dropout, logistics, timelines) Proposal is a “best estimate”. A study true-up should be reviewed at an agreed upon enrollment goal.

Work Order Work Order Process Typically a Master Services Agreement (MSA) is signed Company specific – either LOI or full work order Final protocol required, proposal update recommended Work Order Template – typically part of MSA

III. Hitting Kits on Site Date: Key Milestones Lab setup times range from 4 – 8 weeks depending on complexity of study Final Protocol Sponsor/CRO availability/input Input on specification document, lab manual Final signatures before kits can go into production, requisitions completed or database developed Site lists a week before kits on site Setup – Process, Timelines, Deliverables and Key Documents Earlier we arrive at finalized specifications, the sooner we start and move study into production.

Setup Process Sponsor/CRO Driven 4-8 Weeks Kits Sent to Sites Study Award Spec Doc Finalization Study in Production Sponsor/CRO Driven 4-8 Weeks Kits Sent to Sites Determine Protocol Requirements Key Deliverables to Ensure Setup Timeline Set Up Procedures: Test set up Database Development Validation Kit Design Lab Manual Site Entry Variability in timeline: Status of protocol Finalizing central lab requirements Final site list Contact details: CRAs Contact details: broker and importer Highlight that client deliverables of final protocol and final central labs requirements are key. Additionally, final site list, CRA contact info, broker and importer contact info. Kits are sent to sites based upon final site list… Commencement of the Data Management Agreement (DMA)

IV. Budget Versus Actuals Proposal/Work order best estimate based on sites/countries/patients provided. Billed on actuals If study parameters change on something that affects the budget (e.g. database lock extended, country change, test added, patients added, etc.), the budget should be amended to reflect the changes. Logistics assumptions – logistics can be up to 40% of your central lab budget Forecasting – Central lab requires study data to forecast. Central lab cannot predict what is happening in your study but can help and provide input to this process. Interim analysis points are key to checking reality versus proposed.

V. Best Practices for Including Central Laboratory in Study Timing – involve Central Lab as soon as possible even if only a synopsis is available Ask for help early in protocol development to determine the proper testing requirements that meet your study endpoints Sponsor/CRO review on proposal / central lab specification document to ensure understanding of what central lab is proposing versus requirements of the study Communication throughout the process: from proposal, through contract through life of study Actuals versus proposed: Joint review/forecast of financials or a “true-up” during the study

V. Summary Main feeding of central lab – INFORMATION - Timely, Early Good information required to give you best possible proposal and most efficient work processes. Engage us early, leverage our expertise Ask us questions; let us make recommendations HELP US HELP YOU – only as good as information you give us Start at the End – what are the outcomes you want