Conducting protocol-based assessments in the Mini-Sentinel pilot - - PowerPoint PPT Presentation

1

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

2

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

3

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

4

Institute for Health, Health Care Policy & Aging Research

Mini-Sentinel partner organizations

5

Process to conducting a MS protocol-based assessment

Workgroup prepares final report & posts it on website Workgroup implements the protocol Workgroup develops a protocol, invites public comment via MS website. Final version posted. Operations Center issues a workgroup opportunity FDA identifies topic

6

Mini-Sentinel distributed analysis

Review & Run Query Review & Return Results

Data Partner 1

Mini-Sentinel Secure Network Portal

1

Mini-Sentinel Operations Center

Enrollment Demographics Utilization Pharmacy Etc

1 Workgroup creates and submits query (a computer program) 2 Data partners retrieve the query 3 Data partners review and run query against their local data 4 Data partners review results 5 Data partners return results via secure network 6 Results are aggregated and returned

2 3 4 5 6

Review & Run Query Review & Return Results

Data Partner N

Enrollment Demographics Utilization Pharmacy Etc

3 4

7

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

8

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 ß-blockers 1,592,278

9

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

10

Timeline

Kick-off meeting 1st workplan sent Analysis complete Draft final report

Mar 11 Sep 11 Jan 12 Feb 12

Total time from start to completion: ~11 months

Aug 11

Protocol finalized

11

Results

0.5 1.0 2.0 4.0 8.0

Adjusted relative risk

ACEIs ARBs Aliskiren

Mini-Sentinel Literature

* Beta-blockers as the common reference group

Toh et al, Arch Intern Med 2012;172:1582-1589

12

Results

0.5 1.0 2.0 4.0 8.0

Adjusted relative risk

ACEIs ARBs Aliskiren

Mini-Sentinel Literature

* Beta-blockers as the common reference group

Toh et al, Arch Intern Med 2012;172:1582-1589

13

Results

0.5 1.0 2.0 4.0 8.0

Adjusted relative risk

ACEIs ARBs Aliskiren

Mini-Sentinel Literature

* Beta-blockers as the common reference group

Toh et al, Arch Intern Med 2012;172:1582-1589

14

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-medical- product-assessment-webinar

15

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

16

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

17

Thank you