Conducting protocol-based assessments in the Mini-Sentinel pilot Process & Lessons learned Darren Toh, ScD Department of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute On behalf of the Mini-Sentinel angioedema workgroup January 31, 2013 1
Mini-Sentinel angioedema workgroup Name Affiliation Role Marsha Reichman OSE/CDER/FDA Co-Lead Monika Houstoun OSE/CDER/FDA Co-Lead Sean Hennessy University of Pennsylvania Co-Lead Darren Toh Harvard Pilgrim Health Care Institute Co-Lead Xiao Ding OTS/CDER/FDA Member Adrian Hernandez Duke University School of Medicine Member Mark Levenson OTS/CDER/FDA Member Lingling Li Harvard Pilgrim Health Care Institute Member Carolyn McCloskey OSE/CDER/FDA Member Azadeh Shoaibi OMP/CDERFDA Member Mary Ross Southworth OND/CDER/FDA Member Eileen Wu OSE/CDER/FDA Member Gwen Zornberg OSE/CDER/FDA Member 2
Overarching goals of the project To assess selected drug-event associations Drugs targeting renin-angiotensin-aldosterone system & angioedema To build general strategies for safety assessments of medical products on the market for >2 years NOT designed to provide definitive evidence of a causal relation 3
Mini-Sentinel partner organizations Institute for Health, Health Care Policy & Aging Research 4
Process to conducting a MS protocol-based assessment FDA identifies topic Operations Center issues a workgroup opportunity Workgroup develops a protocol, invites public comment via MS website. Final version posted. Workgroup implements the protocol Workgroup prepares final report & posts it on website 5
Mini-Sentinel distributed analysis 1 Mini-Sentinel Operations Center Mini-Sentinel Secure Network Portal 6 1 Workgroup creates and submits query (a computer program) Review & Run Query 2 3 Data Partner 1 Enrollment Demographics Utilization Pharmacy Etc Review & Return Results 4 5 2 Data partners retrieve the query 3 Data partners review and run query against their local data 4 Data partners review results Review & Run Query 3 Data Partner N Enrollment Demographics Utilization Pharmacy Etc Review & Return Results 4 5 Data partners return results via secure network 6 Results are aggregated and returned 6
Cohort creation Total population in Mini- Sentinel as July 2011 ~99,000,000 Applying eligibility criteria (age, medical history, etc) ACEIs 1,845,138 ARBs 467,313 Aliskiren 4,867 7
Cohort creation Total population in Mini- Sentinel as July 2011 ~99,000,000 Applying eligibility criteria (age, medical history, etc) ACEIs ARBs Aliskiren ß-blockers 1,845,138 467,313 4,867 1,592,278 8
Statistical analysis Propensity score approach Condensing information from a large number of variables into a non-identifiable measure Case-centered approach and meta-analysis Needing only aggregated data to complete the analysis 9
Timeline 1 st workplan sent Analysis complete Draft final report Kick-off meeting Protocol finalized Mar 11 Aug 11 Sep 11 Jan 12 Feb 12 Total time from start to completion: ~11 months 10
Results 8.0 Mini-Sentinel Literature Adjusted relative risk 4.0 2.0 1.0 ACEIs ARBs Aliskiren 0.5 * Beta-blockers as the common reference group Toh et al, Arch Intern Med 2012;172:1582-1589 11
Results 8.0 Mini-Sentinel Literature Adjusted relative risk 4.0 2.0 1.0 ACEIs ARBs Aliskiren 0.5 * Beta-blockers as the common reference group Toh et al, Arch Intern Med 2012;172:1582-1589 12
Results 8.0 Mini-Sentinel Literature Adjusted relative risk 4.0 2.0 1.0 ACEIs ARBs Aliskiren 0.5 * Beta-blockers as the common reference group Toh et al, Arch Intern Med 2012;172:1582-1589 13
More results can be found here Report: http://www.mini- sentinel.org/work_products/assessments/mini- Sentinel_Angioedema-and-RAAS_Final-Report.pdf Manuscript: http://archinte.jamanetwork.com/article.aspx?articleid=139 1058#qundefined Presentation: http://www.brookings.edu/events/2012/10/16-medicalproduct-assessment-webinar 14
Summary of overarching goal #1 Largest assessment on this topic to date Replicated known ACEIs angioedema association With much more precise risk estimates Provided new information on angioedema risk for Aliskiren (caveat: based on 7 exposed cases) ARBs 15
Summary of overarching goal #2 Developed a time and cost efficient process to perform medical product safety assessments within a large distributed data system Developed analytic strategies to perform robust statistical analysis without sharing identifiable information 16
Thank you 17