# Presentation: 750232

- Update on the New FDA Office of Postmarketing Drug Risk Assessment (OPDRA)1999 DIA Annual Meeting
- Beyond Spontaneous Reports
- Evelyn M. Rodriguez, MD, MPH
- Director, Division of Drug Risk Evaluation II

## Office of

**Extramural Data Sources - Beyond Spontaneous Reporting**

**Office of**
**Post-marketing**
**Drug Risk**
**Assessment**

## Beyond Spontaneous Reports

**Extramural Drug Data Sources**
**IMS Health**
***Prescribing Practices***
***Drug Exposure Data***
***Reporting Rate Estimates***

**Notes:**
The Cooperative Agreements are used to conduct studies to provide data on incidence rates and conduct case control stuides to identify risk factors, and we can conduct cohort studies to look prospectively at outcomes.

IMS America is our source for drug use information. Various Audits:
	1. National Disease and Therapeutic Index (NDTI): 		which provides drug use information linked with 		demographic data

	2. National Prescription Audit (NPA) which provides 	drug sales data

## Beyond Spontaneous Reports

**Extramural Drug Data Sources**
**Cooperative Agreements **
***Incidence Studies***
***Risk Factor Identification***
***Labeling Compliance Studies***
***Off Label Use***

**Notes:**
Drug usage and exposure data help us estimate the drug exposed population and its size.  When use  with spontaneous reports we can use these data to refine the signals of adverse drug reactions.  

Record-linked Databases, Comparators, Interactions 
Examples
1. Record-linked databases: We currently have 5 cooperative agreements with access to administrative and clinical data. In these databases we can look at outpatient prescriptions, ICD-9 codes and review medical records for other health outcomes.  

2. Comparators: Comparing drugs within a class or with similar prescribing indications

3. Interactions: We can look at drug-drug-interactions and drug-disease interactions

## Beyond Spontaneous Reports: Compliance Study 

***Troglitazone and Liver Failure***
***Last labeling change: monthly liver function testing for 8 months***
**1,411 patients exposed**
**45% baseline test**
**Percent Compliance: **
**	****Month 1 - 9.3, Month 2 -  4.2,**
**	****Month 3 - 2.7, Month 4 - 0.5**

## Beyond Spontaneous Reports: Incidence Study

***Troglitazone and Liver Failure***
**Phase 1: Claims Data**
** ****3 of 9,369 total exposed persons**
** ****3 of 616 x 10****6 ****person-years**
**Phase 2: Medical Record Abstraction for Liver Failure Case Validation**** **

## Data Mining

**Building on ongoing work in CDER**
**Creating a multidisciplinary team **
**Beginning formalization of data-mining techniques for signal detection into the AERS**** **

## Data Mining

**Evaluate its utility to target and refine signal detection and evaluation **
**Evaluate its utility in the assessment of risk factors****	**
**age and sex adverse events and **
**identification of drug-drug interactions***** ***

## Beyond Spontaneous Reports: Active Surveillance

***Acute, Severe, Hepatotoxicity Active Surveillance Program (ASH)***
**United Network for Organ Sharing Program funded by HRSA**
**Determine drug exposure history among liver transplant candidates**

## Beyond Spontaneous Reports: Active Surveillance

***Death Certificate Active Surveillance Project***
**NCHS Death Certificates**
**Obtain an annual data tape to determine death rates and demographic data of deaths due to drugs**

## Beyond Spontaneous Reports: Active Surveillance

***National Electronic Adverse Event Surveillance System***
**National Electronic Injury   Surveillance System funded by the Consumer Product Safety Commission **
**Determine incidence of  ADRs among emergency room patients**

## Beyond Spontaneous Reports: Active Surveillance

***Drug Use and Pregnancy Outcomes in Record-Linked Databases***
**Drug Use and Pregnancy Outcomes**
**Develop linkage of maternal and infant records in existing databases **
**Validate the linkage through medical records and vital records**
**Pilot the use of the database as a tool for drug use in pregnancy and infant outcomes**

## Beyond Spontaneous Reports: Active Surveillance

***Centralized Registry of Drug Exposure During Pregnancy***
**Establish the creation of a single registry of prospective drug exposures during pregnancy with collection of infant outcomes**
**Collaboration with CDC**

## Beyond Spontaneous Reports: Active Surveillance

***Active Postmarketing Surveillance Methods in Hospitals***
**Development of work to establish a system for identification of device and drug ADRs**
**Collaboration with CDRH**

## Beyond Spontaneous Reports: Active Surveillance

***Pilot a Sentinel Adverse Drug Reaction Surveillance System***
**Phase 1 - Determine feasibility**
**Hospital Surveillance Study Pilot with CDRH**
**Phase 2 - Pilot population based approach**
**Phase 3 - Establish Sentinel Surveillance System**

## Beyond Spontaneous Reports: Active Surveillance

***Ongoing effort to identify databases and mechanisms tailored for ADRs ***
**Soliciting ideas**
**Identifying funding sources**
**Identifying collaborators**