IMEDS-Evaluation for Conducting Post-Market Safety Studies

Transcription

1 IMEDS-Evaluation for Conducting Post-Market Safety Studies Susan Gruber Troy McCall, Greg Daniel *, Nicole Spear Reagan-Udall Foundation for the FDA * Brookings Institution Big DiP USA, Boston, Massachusetts, September 24, 2015

2 Innovation in Medical Evidence Development and Surveillance (IMEDS) IMEDS is a program of the Reagan-Udall Foundation for the FDA, a non-profit public-private partnership IMEDS-Evaluation supports FDA s public health vision by providing non-fda study sponsors access to data and tools used by the FDA Sentinel System to proactively monitor and detect drug safety 1

3 Innovation in Medical Evidence Development and Surveillance (IMEDS) Outline I. Sentinel Overview II. IMEDS Evaluation III. IMEDS-Evaluation Pilot Study IV. Improving the Methodology V. Participating in IMEDS-Evaluation 2

4 Sentinel Overview Mini-Sen nel Distributed Database* q Popula ons with well-defined person- me for which most medically-a ended events are known q 178 million members** q 358 million person-years of observa on me q 48 million people currently accruing new data q 4 billion dispensings q 4.1 billion unique encounters 42 million acute inpa ent stays q 30 million people with >1 laboratory test result *As of July 2014 ** Double counting exists for individuals who change health plans info@mini-sen nel.org 10 slide courtesy of Richard Platt 3

5 Sentinel Overview Collaborating Institutions that also act as Data Partners Harvard Pilgrim Health Care Institute HealthPartners Institute for Education and Research Henry Ford Health System Marshfield Clinic Research Foundation Meters Primary Care Institute Kaiser Permanente Colorado Kaiser Permanente Hawaii Kaiser Permanente Mid-Atlantic Kaiser Permanente Northern California Kaiser Permanente Northwest source: 4

6 Sentinel Overview Mini-Sen nel Distributed Analysis 1- User creates and submits query (a computer program) 2- Data partners retrieve 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 info@mini-sen nel.org 19 slide courtesy of Richard Platt 5

7 IMEDS-Evaluation FDA s original vision for Sentinel includes leveraging the tools and system capabilities for broader public health and safety uses by stakeholders other than FDA IMEDS-Evaluation is working to realize this vision 6

8 Key Features of IMEDS-Evaluation Supporting the vision of Sentinel as a national resource Consistency in Active Surveillance Re-use of the Sentinel Distributed Data Network Transparency Privacy Collaboration 7

9 IMEDS-Evaluation Pilot Study Sponsored by Pfizer Phase I: Governance Policies and Procedures drafted in collaboration with Sentinel Data Partners and Sentinel Operations Center at Harvard Pilgrim Revision will be informed by experience, and incorporate industry-wide input 8

10 IMEDS-Evaluation Pilot Study Phase II: Carry out a study IMEDS Distributed Data Network IMEDS Operations Center IMEDS Data Coordinating Center at Harvard Pilgrim 9

11 IMEDS-Evaluation Pilot Study FDA Reusable Rapid Query Tools Level I CIDA modular programs Cohort Identification and Descriptive Analysis Tool Type 1: Descriptive statistics Type 2: Crude and minimally adjusted association measures Level II programs provide one-time assessment * Level III programs provide sequential analysis * Protocol-based assessments * *not part of the Pilot, but available when Evaluation is fully operational 10

12 IMEDS-Methods Program Improve safety surveillance using large databases Address challenges fragmented healthcare system, rare exposures/outcomes, generalizability, data capture Activities Methodologic investigations Development of novel tools and methods Informs IMEDS-Evaluation, Sentinel activities, other studies of administrative data 11

13 IMEDS-Methods Program Core focus areas (2015 Research Agenda) 1. Addressing bias in estimates from observational studies 2. Better understanding uses and limitations of the data 3. Expanding the surveillance question to continuous Risk/Benefit assessment 4. IMEDS Research Lab supports qualified investigators from industry, government, and academic institutions 12

14 IMEDS-Methods Program Sample project addressing bias in large scale observational studies Identifying Health Outcomes in Healthcare Databases Clinical, database, methodologic considerations Validation, transportability, best practice Cross-sector effort Stephan Lanes, Kevin Haynes, and Michael Pollack (HealthCore), Alec Walker (WHISCON, IMEDS), Jeff Brown (Harvard Pilgrim) 13

15 IMEDS-Methods Program Sample projects addressing uses and limitations of the data 1. Extract lessons from OMOP activities for Mini-Sentinel Common Data Model comparison Recreate Mini-sentinel protocol-based findings in the IMEDS Research Laboratory identify any discrepancies evaluate sources of heterogeneity 14

16 IMEDS-Methods Program Sample projects addressing uses and limitations of the data 2. Understanding characteristics that facilitate and challenge investigations using administrative data Characteristics of exposure, outcome, data capture Unmeasured confounding, misclassification, loss to follow-up, etc. Joint IMEDS / FDA / MS Workgroup 15

17 IMEDS-Methods Program Translate findings into practice For example, identifying influential characteristics makes it possible to Develop metrics Assess likelihood of success using available data Illuminate barriers Opportunity to refine study design and analysis plan to improve interpretability, reliability 16

18 IMEDS-Methods Program Translate findings into practice Sensitivity Analysis Investigate alternate risk windows, effects of model misspecification, unmeasured confounding Encourage use of more sophisticated approaches Assess impact of any observed variation on substantive conclusion Working to improve the state of the art 17

19 Participating in IMEDS-Evaluation Input on draft Policy and Procedures Draft document will be posted on the IMEDS website with request for public feedback after conclusion of the Pilot with subject line "Evaluation Program updates, requests for your input Troy McCall, IMEDS Chief Implementation Officer 18

20 Conclusion IMEDS-Evaluation is working to provide non-fda study sponsors access to same data and tools as Mini-Sentinel IMEDS-Methods is focusing on ways to improve the reliability and interpretability of large scale observational studies Stakeholder participation is vital to success Get involved by ing with subject line "Evaluation 19