6/30/2015 Global Trials- Industry Perspective Thomas P. Haverty, MD Group VP Global Clinical Research SPRI

26/30/2015Presentation Name Globalization The world has globalized and so has the pharmaceutical industry Since we have to defend our data to all Health Authorities, it is in our interest to get highest quality data Patient availability and recruitment rates impact our development programs Cost/patient and infrastructure costs are similar across geographies We conduct trials globally to achieve quality and efficiency, not cost advantage

36/30/2015Presentation Name Country Selection-Guiding Principles Data Quality Ethical Conduct Patient availability Infrastructure Cost

46/30/2015Presentation Name Data Quality Assessed by country/region Correlates with quality of PI and site, not be geography per se Recent centralized best spirometry by central reviews in Phase III Respiratory program showed 97 % acceptable maneuvers in Colombia, Serbia and Thailand, 83 % in India and 79 % in US In Allergy and CNS studies in Europe have consistently shown larger effect sizes than in US Industry has genuine interest in generating good quality data, which are associated with lower variability and higher effect sizes

56/30/2015Presentation Name Managing Ethical Concerns On occasion Health Authorities (HAs) have different objectives than Ethics Committees (ECs) For a Respiratory program using inhaled steroid and beta- agonist, FDA mandated placebo and beta-agonist only arm Many EU ECs did not allow placebo arm Sponsor added sites in Eastern Europe and Latin America to get required N of subjects

66/30/2015Presentation Name Patient Availability Assessed in feasibility studies and chart reviews Recruitment in recent Respiratory study 0.5 pts/site/mo in US vs 1.8 in Russia To conduct trial solely in US would have taken 3 times as long

76/30/2015Presentation Name Infrastructure If there are pts in a region you must have manpower to run study there For Respiratory program little infrastructure in Eastern Europe Utilized global CRO with same standards as US Conducted audits with equivalent results to US Must defend all data to all HA audits/inspections

86/30/2015Presentation Name Cost In recent respiratory program faster recruitment rates outside US had the biggest impact on containing overall costs Investigator grants were % of US rates Other costs (monitoring, labs) were 125 to 160 % of US costs No cost advantage per pt going outside US Program became feasible by meeting recruitment goals, driven by faster rates outside US

96/30/2015Presentation Name Summary The world has globalized and so has the pharmaceutical industry Since we have to defend our data to all Health Authorities, it is in our interest to get highest quality data Patient availability and recruitment rates impact our development programs Cost/patient and infrastructure costs are similar across geographies We conduct trials globally to achieve quality and efficiency, not cost advantage