examples of ade surveillance systems meddra ® processing of adverse event reports in ade...

Examples of ADE Surveillance Systems

MedDRA® Processing of Adverse Event Reports in ADE Surveillance SystemsAmarilys Vega, M.D, M.P.H., Sonja Brajovic, M.D., Jung Lee, RPh, Mark Vieder, RPh., Bane Bradic, M.D., PSI International, Inc., USA

Data Coding and Coding Quality ControlDevelop and implement coding and quality control guidelines

Safety Signal GenerationReconcile and compare clinical trials and postmarketing

safety dataSearch organization’s safety data and data from other

sources for potential signals (i.e., data mining)

Safety Signal Evaluation ActionsAssess clinical relevance of safety signalTake the necessary steps to improve drug safety

Descriptive EpidemiologyDescribe and summarize all available information pertaining to the adverse event of interest and the suspect product

Objective: To describe the application of the Medical Dictionary for Regulatory Activities terminology (MedDRA® ) in the drug safety surveillance process by providing an overview of the different phases of this process and examples of surveillance systems that employ MedDRA® .

Analytic EpidemiologyVerify identified safety signals by means of observational and/or experimental epidemiological studies

Data Collection, Entry, and Storage

Collect, enter, and store in database detailed safety data obtained from all possible venues

VHA PBM ADE Program ( Veterans Health Administration Pharmacy Benefits

Management Adverse Drug Event Database)

Passive surveillance system which collects spontaneous adverse event data from all VA medical centers and is managed by the PBM VHA office

Coding Guidelines and Coding Practices: Impact on the Accuracy, Consistency & Uniformity in MedDRA® Coding

Example of an Adverse Event NarrativeA patient started a new antibiotic for the treatment of a complicated urinary tract infection 3 days ago. He took a double dose last night by mistake. Today he reports markedly increased blood glucose with high urinary glucose. Prior to this, the patient has been stable on once daily oral anti-diabetics.

Coding* by Organization A1. LLT Incorrect dose administered

PT Incorrect dose administeredSOC Injury, Poisoning and Procedural

Complications2. LLT Loss of control of blood sugar

PT Diabetes mellitus inadequate controlSOC Endocrine Disorders/SOC Metabolism and Nutrition Disorders

1. LLT Incorrect dose administeredPT Incorrect dose administeredSOC Injury, Poisoning and Procedural Complications

2. LLT Blood glucose increasedPT Blood glucose increasedSOC Investigations

3. LLT Glucose urine highPT Glucose urine presentSOC Investigations

4. LLT Medication ErrorPT Medication ErrorSOC Injury, Poisoning and Procedural Complications

1. LLT Incorrect dose administeredPT Incorrect dose administeredSOC Injury, Poisoning and Procedural Complications

2. LLT Diabetes mellitus aggravatedPT Diabetes mellitusSOC Endocrine Disorders/SOC Metabolism and Nutrition

Disorders

Coded in Other

Terminologies

MedDRA®

Conversion

Clinical Trials Data

Clinical Trials Data

MedDRA®

Coded Data

Organization’s Postmarketing

Safety Data

Compare data from these sources and determine which combination of MedDRA®

terms suggest a potential safety signal for a particular product

Other Sources of Safety Data

+

NEISS-CADES(National Electronic Injury Surveillance System -Cooperative Adverse Drug Event Surveillance)*

Active surveillance system which collects adverse reaction data from patients’ records in a nationally representative sample of hospital emergency rooms.

Case 1 Case 2 Case 3 Case 4 Case n

Create a Case Series

Create a “Case Definition”Using MedDRA® Terms

Identify cases of interest in large external databases (other standard terminologies are

bridged to MedDRA® )

ObservationalStudies

ExperimentalStudies

Verify Safety Signal

At each participating hospital emergency room, Center for Disease Control and Prevention (CDC)/Consumer Product Safety Commission (CPSC) trained coders review all patient records in search for adverse drug events. Data on relevant cases, including codes for injuries and mechanisms of injury, are entered into a standardized database and subsequently processed by a contractor who codes this information using MedDRA® (MMWR, April 22, 2005 / 54(15);380-383; Ann Emerg Med. 2005;45:197-206).

Coding guidelines developed based on MedDRA® Term Selection: Points to Consider document and VA’s specific objectives. The goal is to capture in MedDRA® terms adverse event data as close to the reporter’s verbatim as possible.

MedDRA® coding is applied to the stated Indications for Treatment, Medical History, Adverse Events, and Laboratory results not represented by the Diagnosis and Medical History.

In process of developing standardized methods to process and evaluate aggregate safety data .

Currently undergoing further development and evaluation to determine extent of use as a tool in drug safety surveillance.



Organization's Specific Coding GuidelinesThis process should be guided by the ICH endorsed

MedDRA® Term Selection: Points to Consider document and the organization’s specific objectives

Coding* by Organization BCoding* by Organization C

Drug Safety Surveillance Process Overview

MedDRA® Application and Challenges

FDA AERS(Food and Drug Administration

Adverse Event Reporting System)

Passive surveillance system which collects spontaneous adverse event data submitted by manufacturers and directly by consumers and health professionals.

Coding guidelines developed based on ICH endorsed MedDRA® Term Selection: Points to Consider document and FDA’s coding principles. The goal is to capture medical concepts described in the narrative and translate them into suitable MedDRA® terms. Coding guidelines and practices are regularly reevaluated and modified according to FDA’s needs and requirements.MedDRA® coding accuracy is monitored by a continuous quality assurance process.

Safety data collected during clinical trials are incorporated into the product’s approved label. FDA reviewers monitor products’ safety profiles. They search for safety signals by reviewing AERS data, case reports found in medical literature, and data from other passive and active surveillance systems. Most of these data are coded in MedDRA®. One of the tools employed by the FDA to identify safety signals is data mining. In-depth knowledge of MedDRA® required for effective data mining.

Reviewers:• Create a case definition using MedDRA® terms that describe the clinical process of interest and create a search group containing all possible names given to the suspect product. • Create a case series by retrieving from AERS all cases fulfilling case and product definitions. Add literature cases to case series.• Evaluate raw data from individual case reports and extract all relevant case data stratifying information as necessary. • Provide a clinical assessment of the findings based on the nature of the disease under treatment and adverse event characteristics.

Collected data must be ascomplete and detailed as possible to facilitate clinical interpretation, MedDRA® coding, and data retrieval and analysis.

Duplicate reports and follow up data must be carefully handled.

Employ information technology tools that will support this phase as well as other phases of the Drug Safety Surveillance process.

Clinical Trials Data+ +

Organization’s Safety Data

Data Retrieval

Other Sources of Safety Data

(i.e., medical literature, WHO)

Clinical assessment Summarize

all case information

Obtain adverse event’s typical

characteristics

data

Enhance dataset

by abstracting additional information

Obtain disease

natural history data

When possible, code in MedDRA®

Descriptive Epidemiology Studies

In-depth analysis


•Regulatory actionsDevelop product-specific Risk Management plan Assess safety issue’s impact on patient support and disease management programs

•Assess impact on product marketing

•Make recommendations on how to improve MedDRA®Terminology

Scientists from within FDA and from other organizations conduct experimental and observational studies (large population-based databases). Use of MedDRA® depends on the characteristics of the study database and the existence of terminology bridges between MedDRA® and study database’s particular terminology (ICD, SNOMED, etc.).

FDA provides:• Continuous assessment of new safety data and it’s impact on patient safety.• Drug safety surveillance process guidelines. • MedDRA® terminology improvement recommendations.

In process of developing standardized methods to process and evaluate aggregate safety data .

Additional MedDRA® encoded data facilitates search for potential safety signals and their interpretation.

In process of developing standardized methods to evaluate aggregate safety data .

In process of developing standardized methods to evaluate aggregate safety data .

* MedDRA version 8.0** A Center for Disease Control and Prevention (CDC), Consumer Product Safety Commission (CPSC), and Food and Drug Administration (FDA) joint project

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