Tiffany Woodworth

Design considerations, architecture, and use of the Mini-Sentinel distributed data system

We describe the design, implementation, and use of a large, multiorganizational distributed database developed to support the Mini‐Sentinel Pilot Program of the US Food and Drug Administration (FDA). As envisioned by the US FDA, this implementation will inform and facilitate the development of an active surveillance system for monitoring the safety of medical products (drugs, biologics, and devices) in the USA.

Electronic clinical laboratory test results data tables: lessons from Mini-Sentinel

Developing electronic clinical data into a common data model posed substantial challenges unique from those encountered with administrative data. We present here the design, implementation, and use of the Mini‐Sentinel Distributed Database laboratory results table (LRT).

Successful Comparison of US Food and Drug Administration Sentinel Analysis Tools to Traditional Approaches in Quantifying a Known Drug‐Adverse Event Association

The US Food and Drug Administrations Sentinel system has developed the capability to conduct active safety surveillance of marketed medical products in a large network of electronic healthcare databases. We assessed the extent to which the newly developed, semiautomated Sentinel Propensity Score Matching (PSM) tool could produce the same results as a customized protocol‐driven assessment, which found an adjusted hazard ratio (HR) of 3.04 (95% confidence interval [CI], 2.81–3.27) comparing angioedema in patients initiating angiotensin‐converting enzyme (ACE) inhibitors vs. beta‐blockers. Using data from 13 Data Partners between 1 January 2008, and 30 September 2013, the PSM tool identified 2,211,215 eligible ACE inhibitor and 1,673,682 eligible beta‐blocker initiators. The tool produced an HR of 3.14 (95% CI, 2.86–3.44). This comparison provides initial evidence that Sentinel analytic tools can produce findings similar to those produced by a highly customized protocol‐driven assessment.

Sentinel Modular Program for Propensity Score–Matched Cohort Analyses: Application to Glyburide, Glipizide, and Serious Hypoglycemia

Sentinel is a program sponsored by the US Food and Drug Administration to monitor the safety of medical products. We conducted a cohort assessment to evaluate the ability of the Sentinel Propensity Score Matching Tool to reproduce in an expedited fashion the known association between glyburide (vs. glipizide) and serious hypoglycemia. Thirteen data partners who contribute to the Sentinel Distributed Database participated in this analysis. A pretested and customizable analytic program was run at each individual site. De-identified summary results from each data partner were returned and aggregated at the Sentinel Operations Center. We identified a total of 198,550 and 379,507 new users of glyburide and glipizide, respectively. The incidence of emergency department visits and hospital admissions for serious hypoglycemia was 19 per 1000 person-years (95% confidence interval = 17.9, 19.7) for glyburide users and 22 (21.6, 22.7) for glipizide users. In cohorts matched by propensity score based on predefined variables, the hazard ratio (HR) for glyburide was 1.36 (1.24, 1.49) versus glipizide. In cohorts matched on a high-dimensional propensity score based on empirically selected variables, for which the program ran to completion in five data partners, the HR was 1.49 (1.31, 1.70). In cohorts matched on propensity scores based on both predefined and empirically selected variables via the high-dimensional propensity score algorithm (the same five data partners), the HR was 1.51 (1.32, 1.71). These findings are consistent with the literature, and demonstrate the ability of the Sentinel Propensity Score Matching Tool to reproduce this known association in an expedited fashion. See video abstract at, http://links.lww.com/EDE/B275.

Complementary use of passive surveillance and Mini-Sentinel to better characterize hemolysis after immune globulin.

Hemolysis after intravenous immune globulins (IGIVs) is a known complication, but expanding indications and recent manufacturing changes warrant ongoing postmarketing surveillance. Characterization of post‐IGIV hemolysis to date has been limited to small case series.

Prospective surveillance pilot of rivaroxaban safety within the US Food and Drug Administration Sentinel System

The US Food and Drug Administrations Sentinel system developed tools for sequential surveillance.

Early impact of the ICD-10-CM transition on selected health outcomes in 13 electronic health care databases in the United States

To describe the consistency in the frequency of 5 health outcomes across the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) and Tenth Revision, Clinical Modification (ICD‐10‐CM) eras in the US.

Assessing the impact of the new ICD-10-CM coding system on pharmacoepidemiologic studies-An application to the known association between angiotensin-converting enzyme inhibitors and angioedema

To replicate the well‐established association between angiotensin‐converting enzyme inhibitors versus beta blockers and angioedema in the International Classification of Diseases, 10th Revision, Clinical Modification (ICD‐10‐CM) era.

Evaluation of the US Food and Drug Administration sentinel analysis tools in confirming previously observed drug-outcome associations: The case of clindamycin and Clostridium difficile infection

The Food and Drug Administrations Sentinel System developed parameterized, reusable analytic programs for evaluation of medical product safety. Research on outpatient antibiotic exposures, and Clostridium difficile infection (CDI) with non‐user reference groups led us to expect a higher rate of CDI among outpatient clindamycin users vs penicillin users. We evaluated the ability of the Cohort Identification and Descriptive Analysis and Propensity Score Matching tools to identify a higher rate of CDI among clindamycin users.

PS2-14: Organizing and Tracking Multi-site Data Network Project Activities

Background/Aims Multi-site, multi-purpose networks such as the HMO Research Network consortia projects and the FDA Mini-Sentinel need an efficient mechanism to track project activities and specific queries, organize local resources, and create a searchable index to enable communication of lessons learned and re-use of resources. To this end, the Mini-Sentinel Operations Center (MSOC) has created the Mini-Sentinel Data Catalog (MSDC) to track all Mini-Sentinel projects. Methods The MSDC is a system designed to capture and organize the key meta-data of all MSOC querying activities, to provide a catalog of all data partner (DP) activity, to allow rapid reporting of key metrics, and to enable Mini-Sentinel users to quickly identify the location and relevant information for all data queries. The system is integrated into the Mini-Sentinel secure file transfer system, so when new results for data queries are uploaded to the secure transfer site the MSDC processes an automatically generated email with the relevant information that is then incorporated into the tracker. The system allows MSOC to view the query responses and mark them as accepted or rejected. The MSDC allows users to create notes associated with all projects and subtasks, and enables easy filtering to track the status of results by query ID, DP or status, and the creation of reports on the history of each. The system incorporates role based access control with a variety of editing and reporting privileges that can be set by user. Results The MSOC has completed beta-testing of the MSDC, and is using the system to track 25 individual projects facilitating rapid access to useful meta-data, providing MSOC with a simple tool to manage and track >250 individual DP responses. Discussion MSOC plans to use the MSDC to track future projects submitted to DPs. It will be expanded to accommodate a more diverse set of project types and to more seamlessly handle uploads to the Mini-Sentinel secure file transfer system. The system will also be integrated into the Mini-Sentinel distributed query tool that is based on the PopMedNet software platform, creating an integrated distributed querying and management platform.