RBM: Getting Beyond the Promise and Getting To Value SCOPE Conference, February 2019 Gary Thompson, VP Strategic Consulting, Medidata Solutions

RBM: Lots of Promise… Where’s the Value? May 2013: Current model for RBM laid out in TransCelerate whitepaper Nov 2016: Reinforced and formalized in regulations with release of ICH E6:R2 July 2018: 32% of industry respondents have yet to develop an approach to KRIs* Nov 2018: FDA concerns with slow industry adoption of risk-based approaches and realizing speed and cost benefits** * “Risk-based Monitoring: Widespread Implementation is Underway, but Still Messy”, CenterWatch Weekly, July 9, 2018 ** “Harnessing Real World Evidence for Safety and Innovation”, Scott Gottlieb, M.D., Commissioner of Food and Drugs, Remarks to Reagan-Udall Foundation, November 19, 2018

Why Haven’t Companies Seen Enough Value to Pursue RBM More Aggressively? Companies miss value in RBM for one of three reasons Confusion about what RBM is and how they should be implementing it Uncertainty over what their RBM value proposition is Challenges with the discipline, time and resources required to implement and execute RBM at scale

Clarifying RBM: What It Is Iteration Risk Assessment KRIs QTLs Ongoing Monitoring Quality Report Statistical/Analytical Approaches Planning Execution Outcomes Remote Monitoring Where Central Monitoring How Risk-based Monitoring Why ICH E6:R2 Trial-Level Quality/Integrity Trial-Level Quality/Integrity Strategic KRIs Risk Assessment AI/ML Data Point-Level Quality/Integrity Tactical Data-Point -Level Quality/Integrity Traditional Approaches Analytics-Powered Approaches

Clarifying RBM: How It Works Trial-Level Quality/Integrity Trial-Level Quality/Integrity Strategic View Risk Assessment KRIs AI/ML Data Point-Level Quality/Integrity Tactical View Data Point-Level Quality/Integrity Risk-Based and Analytics-Powered Approaches Traditional Approaches Trial-Level Quality/Integrity Trial-Level Quality/Integrity Trial-Level Quality/Integrity Trial-Level Quality/Integrity Trial-Level Quality/Integrity Trial-Level Quality/Integrity Trial-Level Quality/Integrity Trial-Level Quality/Integrity Strategic Trial-Level Quality/Integrity Trial-Level Quality/Integrity Strategic Trial-Level Quality/Integrity Strategic Trial-Level Quality/Integrity Strategic Strategic KRIs Risk Assessment Strategic KRIs Risk Assessment KRIs Risk Assessment KRIs Risk Assessment KRIs Risk Assessment KRIs Risk Assessment AI/ML AI/ML AI/ML AI/ML AI/ML AI/ML Data Point-Level Quality/Integrity Data Point-Level Quality/Integrity Data Point-Level Quality/Integrity Tactical Data Point-Level Quality/Integrity Tactical Data Point-Level Quality/Integrity Tactical Data-Point -Level Quality/Integrity Data Point-Level Quality/Integrity Tactical Data-Point -Level Quality/Integrity Tactical Data-Point -Level Quality/Integrity Tactical Data-Point -Level Quality/Integrity Data-Point -Level Quality/Integrity Data-Point -Level Quality/Integrity Traditional Approaches Analytics-Powered Approaches Traditional Approaches Analytics-Powered Approaches Traditional Approaches Analytics-Powered Approaches Traditional Approaches Analytics-Powered Approaches Traditional Approaches Analytics-Powered Approaches Traditional Approaches Analytics-Powered Approaches

How RBM Generates Value “Perfect” Wasted Effort Target (KRI) QTL Valuable Effort Quality (eg., protocol compliance, data quality, etc) Cost ∞ (eg., financial, human resources, time, delays to patients)

How RBM Generates Value Cost Quality (eg., protocol compliance, data quality, etc) (eg., financial, human resources, time, delays to patients) ∞ “Perfect” Target QTL Wasted Effort Valuable Company A (overinvestment in quality activities) Consistently meeting safety, quality, and compliance demands, but with excessive burden and time Opportunity to decrease costs while maintaining high quality Investment exceeds risk = Wasted efforts Risk exceeds investment = Quality gap Optimal risk-based quality investment Company B (underinvestment in quality activities) Concerned about / unsure of consistent quality and compliance delivery, but challenged to make sharply higher investments Opportunity to increase quality with minimum, targeted additional investment Relative Risk (Criticality and Frequency) Various Clinical Trial Processes / Data

Statistical/Analytical A Complete RBM Capability is Worth it… and also Complex, Expensive, Demanding Entry Point – Targeted SDV: Reduce site monitoring costs Iteration Targeted SDV Issues Management Integrated Workflow Risk Assessment KRIs QTLs Ongoing Monitoring Quality Report Statistical/Analytical Approaches RACT Industry: TBD Central Monitoring AI / ML Planning Execution Outcomes Entry Point - Risk Planning and Issues Management: Improve Control of the Quality Process Entry Point – Central Monitoring: Augment quality assurance through analytics ICH E6:R2 Solutions

RBM Value: Achievable with the Right Approach Getting to RBM Value requires clear, smart decisions Get clear on the components of RBM and what’s needed for your goals Be smart about which of the RBM value propositions is right for your company Be decisive on your best path: All-in or start with a specific entry point

Thank you. gthompson@medidata.com