Event-Level Narrative Efficient Safety Assessment in Clinical Trials Using the Computer-Generated AE Narratives of JMP Clinical Richard C. Zink & Drew Foglia JMP Life Sciences, SAS Institute Background Challenges Event-Level Narrative ICH Guideline E3 on the content of clinical study reports (CSRs) recommends that sponsors provide written narratives describing each death, serious adverse event (SAE), and other significant AE of special interest to the disease under investigation. Narratives may shed light on factors associated with severe events, or describe effective means for managing patients for appropriate recovery. We describe how AE narratives can be generated directly from study data sets using JMP Clinical Medical writer has to review disparate data sources Not composed until patients complete study. Rate-limiting factor in completing the CSR. Changes to database may cause incorrect reporting; narrative text updated manually. The volume of events for severe diseases consume a great deal of resources Example Details Nicardipine trial (Haley et al., 1993) has 683 SAEs for 310 patients Sample narrative, which includes laboratory findings, has 409 words At 70 words-per-minute, it would take 5.8 minutes to write To write all narratives: 3991 minutes 67 hours 1.675 full-time equivalent What factors led to the event? What medications, evaluations or tests were associated with the event? Did the patient recover? What factors led to recovery? Was treatment related to the event? Did the patient complete the trial, or did the SAE cause the patient to discontinue the trial or interrupt study therapies?

Returning to the Example Efficient Safety Assessment in Clinical Trials Using the Computer-Generated AE Narratives of JMP Clinical Richard C. Zink & Drew Foglia JMP Life Sciences, SAS Institute Time Estimate Ignores JMP Clinical Narrative Dialog Time estimate ignores Comparing data sources Performing mental calculations Quality control Thinking and reflection Trips for coffee Bathroom breaks Narratives are extremely resource intensive! Dialogs to select narrative options SAS code and Velocity™ (project of the Apache® Software Foundation) templates to build the narrative text Returning to the Example 683 SAE narratives were generated in less than one minute Huge time savings compared to 1.675 FTE! CDISC! Narrative Dialog Subject-level analysis data set (ADSL) Adverse events (AE) Concomitant medications (CM) Demographics (DM) Disposition (DS) Study medication exposure (EX) Healthcare encounters (HO) Medical history (MH) Up to three findings domains, for example ECG test results (EG) Laboratory test results (LB) Vital signs (VS) Conclusions JMP Clinical AE Narratives Accelerates the writing process Improves quality control Allows for additional nuanced detail to be added by the medical writer, including JMP figures Table of contents, watermarks, images Focus on the science Guide appropriate management of patients

Subject-Level Narrative Event-Level Narrative with Tables Efficient Safety Assessment in Clinical Trials Using the Computer-Generated AE Narratives of JMP Clinical Richard C. Zink & Drew Foglia JMP Life Sciences, SAS Institute Subject-Level Narrative Translated Narrative Event-Level Narrative with Tables