Using clinical trial data as real-world evidence Use Cases at the intersection of Real-World Evidence/ OHDSI and Clinical Trials # Type Name Description Data 1 Using clinical trial data as real-world evidence To the degree the study data allows, use clinical trial data as another RWE data source, or epidemiological ‘lens’ into a problem for which RWD has been used to solve previously Answer health outcomes questions Our 1 2 Using insights from RWE data to help clinical trial design or evaluation If RWE includes genomics, using RWE to identify biomarkers to create biomarker-homogenous cohorts to use in ‘patient enrichment’ (especially seen in oncology) phases or types of trials, to understand how to define indications/contra-indications that drive up effectiveness, sometimes referred to as precision medicine Helps design a better trial Our #13 and 6 3 Utilizing RWE data to mimic clinical trial inclusion/exclusion criteria to enhance recruitment by understanding characteristics of the population at large 4 Using insights from clinical trial data to improve RWE studies, insights Characterize the conditions under which RWE should be considered as reliable and valid as evidence from completed/ published clinical trial data Helps define a more relevant network study or RWE analysis sourced from group outside of use-case-thon 5 RWE as validation data set for confirming, enhancing or forming human biological characteristics for a virtual patient cohort in in silico clinical trials, which could extend to predicting how types of patients may respond to a drug or intervention. Perform an in silico clinical trial on a purely RWE data set, using cohort definitions or other insights from the clinical trial and applying it to the RWE dataset with no data linking or joining necessary. Our #19 and 20, and also sourced from group outside of use-case-thon 6 Using RWE informatics to host & analyze clinical trial data to improve future action Use RWE common data model to store/ protect/ standardize cohort definitions at national or organizational level (or other meta- information) to apply to all clinical trials to better enable aggregate or population-level cross-trial analytics Identify insights from clinical trial data {or consider a better value desc] Our #18 Please contact shawn@shawndolley.com with questions.

Use of RWE data retrospectively Use Cases at the intersection of Real World Evidence/ OHDSI and Clinical Trials # Type Name Description Data 7 Using RWE informatics to host & analyze clinical trial data to improve future action Add many completed clinical trials and combine them into a single ‘synthetic’ trial in a common model to perform an in silico clinical trial Identify insights from clinical trial data Our #9 8 Add many completed clinical trials in a common model to perform faster, more efficient analysis on outcomes and operating characteristics, toward future trial design Helps design a better trial Maybe our #9, maybe original 9 Add many completed clinical trials in a common model to perform faster, more efficient analysis on outcomes and operating characteristics, toward comparing single trial to a pool of historical trials 10 Use of RWE data retrospectively Analyze RWE data to evaluate if clinical trial results were generalizable; mapped to patient behavior; the level of effectiveness to what a trial showed for efficacy, other post hoc analysis porting trial result to real world evidence Our #10 11 Using insights from RWE data to help clinical trial design or evaluation Identify alternate treatment arms to include in a trial by mining RWE to find off-label uses for a pathology of study Our # 11 12 Use what RWE data can tell us about burden of disease to predict recruitment during trial to estimate sample size needed, including as specific as select cohort definitions, geographies, other Our #3, #5 Please contact shawn@shawndolley.com with questions.

Use Cases at the intersection of Real World Evidence/ OHDSI and Clinical Trials # Type Name Description Data 13 Using insights from RWE data to help clinical trial design or evaluation Use RWE data and its patient behavior patterns to predict adherence during trial to estimate sample size needed Helps design a better trial (some portion of #2) 14 Understand dosage effects & patterns to educate on best trial dose ranges Our 21 (uses 1 data set to help the other), and 12 15 Search RWE data to validate or predict endpoints or defined outcome measurements (and predict how certain types of patient might respond to a drug) Our 22 part 2 (uses 1 data set to help the other) but not 20 as 20 is in silico, and 12 16 Search RWE data to establish the ‘standard of care’ for new clinical trial Our 22 (uses 1 data set to help the other) 17 Using insights from clinical trial data to improve RWE studies, insights Search a number of clinical trials to extract a universal cohort definition for a RWE study Helps define a more relevant network study or RWE analysis Our 23 (uses 1 data set to help the other) 18 Using matching or linking technology, identify clinical trial participants for whom there is a record in a RWE database, and add trial data about that participant to the fixed RWE dataset, or to join with RWE data during an analytic exercise Answers health outcomes question(s) Sourced from our group outside of use-case-a-thon Please contact shawn@shawndolley.com with questions.