Cdm

Clinical Data Management

Overview

Mission Responsibility Process

1. Discrepancies Management2. Medical Coding and CTCAE

CRF Filling Instructions Reminders

Mission of CDM Consistency Accuracy Validity Archiving

High Quality Data is needed to perform statistical analysis

CRF Entry Cleaning

DM process

Stat. Analysis

Challenge Error rate 0%

Responsibilities of CDM Responsibilities

Protocol Review CRF Design / Review Clinical DB Application Development Computer System Validation CRF tracking Data Entry / Verification Transformation to SAS data Medical Coding : AE, Medication, Medical

condition

Responsibilities of CDM

Responsibilities Audit trails - Transparency DB QA DB Security and Archiving Regular DB backup

CDM Process

Database designDatabase design

Protocol Review & CRF Design/ReviewProtocol Review & CRF Design/Review

Development StageDevelopment Stage

Data validation programData validation program

Data entry applicationData entry application

Pre-entry reviewPre-entry review

Double data entry Double data entry

Data Processing StageData Processing Stage

Unmatched checkUnmatched check

Logical checkLogical check

Discrepancies mgt.Discrepancies mgt.

Closing StageClosing Stage

Medical codingMedical coding

DB lockDB lock

Validation of SAS data set Validation of SAS data set

Transformation to SAS dataTransformation to SAS data

CRFs managementCRFs management

CDM Flowchart

Data Entry

Approved Blank CRF and Protocol

Quality Control of Database and Database go live

Batch Validation

Medical CodingQA/QC of data

CRF Annotation, Edit Specification Document Preparation

Database Lock & Statistical report

generation

Database Design Setup

Test Data Entry

CRF’s completed

at site.

CRF Receipt and Tracking in Data Center

Maintaining Missing & pending pages log Discrepancy Mgt.

Pre-Data Entry Review

Discrepancy Management

Why discrepancy

Types of discrepancy

Methods to resolve discrepancy

Why discrepancy?

Data complete?

Data consistent?

Discrepancy

Data correct?Data logical?

Data legible?

Discrepancy Type

Missing Illegible Range Date Logical

Discrepancy Resolve Methods

Self Evident- discrepancies which are resolved by Data Coordinator. Ex: Details of concomitant medication are given but Yes/No

field are not marked. CRA/Medical Monitor- discrepancies

which are resolved by CRA or Medical Monitor.

Discrepancy Resolve Methods

Query- Discrepancies which are resolved by Investigator.

Ex: Start date of Adverse event not supply.

Query has been send to investigator by Data Clarification Form (DCF)

Medical Coding

Why Medical coding Different sites, Different culture, different time-zones, different

physicians and various other factors leads to variation in the data entered in particular fields which cannot be effectively controlled. This varying fields require coding.

Methods 1. Auto-Coding2. Manually3. Combination of Both

MedDRA

Med = Medical D = Dictionary for

R = Regulatory A = Activities

FDA and EU mandated for AE data coding

Objectives for MedDRA Development An international multi-lingual terminology

Standardized communication between industry and regulators

Support of electronic submissions

Application through all phases of the development cycle

Objectives for MedDRA Development Classification for a wide range of clinical

information

Support for multiple medical product areas

A terminology that saves time, resources, and money

MedDRA Is Designed For Coding: Signs (i.e. Redness) Symptoms (i.e. Dizzy) Diseases (i.e. AIDS) Diagnoses (i.e. Hepatic failure) Therapeutic indications (i.e. Congestive heart

failure) Names and qualitative results of investigations (i.e.

Increased SGOT) Surgical and medical procedures (i.e.

Cholecystectomy) Medical, social, and family history (i.e. Alcoholism)

Not Code able Term A single event description contains multiple conditions. Ex:

Leg red, swollen, and painful An event term contains a diagnosis and a symptom. Ex: Fever

and Cold The event term can be interpreted more than one way. EX:

Unable to focus The event term does not make sense. Ex: Left leg The event term is foreign Event term contains a question mark Improvement of a condition is implied, but the term does not

state it is a benefit. Ex: Sleep improved

CTCAE Common Terminology Criteria for Adverse

Events (CTCAE) They consist of the name of the area of interest

and a grading which refer to the severity of the reaction: grade 1 (mild AE) to grade 5 (fatal)

The actual medical condition may differ depending on the severity criteria

More than one medical condition may be covered by the same CTCAE grade

CTCAE Codes for Abnormal Lab Results

CTCAE v3.0 Term

Grade 1

Grade 2

Grade 3

Grade 4 Grade 5

Prolonged QTc interval

QTc 450 - 470 msec

QTc 481 - 500 msec

QTc >=501 msec on at least two separate EKGs

QTc >=501 or >60 msec change from baseline and Torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia

Death

CRF Filling Instructions Authorized individuals

Block Letters and avoid over writing and writing out side the provided space

Strike off all the blank pages with initial and date.

Do not write in shaded area

Sign and date CRF pages ,where requested

CRF Filling Instructions Subject Initials: Must be the same throughout

the study. If the subject does not have a middle initial, ‘-’ should be used instead of

‘X’. e.g. Brian Jones should be recorded as: |B|-|J|

CRF Filling Instructions Errors:

Error will be cross out with single horizontal line and write correction next to it. Initial and date the correction.

e.g. |1|5|/|0|4|/|2|0|0|4| 2005 CJW 15/04/2005

Wrong practice which is not acceptable |1|5|/|0|4|/|2|0|0|4|

Do not use correction fluid, pencil or red ink. Make Sure that the error, although crossed out, remains legible

CRF Filling Instructions

Dates: Record the actual date of the visit.

The order of entry in the date format is Day, Month, Year (07/01/2007). Day, month and year are to be expressed numerically.

Correct entry for complete date: |0|7|/|0|1|/|2|0|0|7| DD MM Y Y Y Y

In the absence of a precise date for events and therapies that precede the subject’s inclusion into the study, incomplete dates should be recorded as follows:

Correct entry for incomplete date: |N|K|/|N|K|/|2|0|0|2| (NK: Not Known)

Reminders Adverse Event Log: Parasitological Assessment Log: Body Temperature log: Vital Signs Log: Prior and concomitant medication Log: PK Sampling Log: Physical Examination Log: Assessment of clinical Signs and Symptoms Log: 12 Lead ECG Log:

Reminders If ECG is CS or QTc is > 500 msec,

Should be reported as AE.

Any increase in grading of signs and Symptoms from previous day should be reported as AE.

Please exclude the Subject, if axillary temperature is < 37.5 ºC or oral temperature is < 38° C.

Reminders In Clinical Signs and Symptoms, Please enter only One

CTCAE Grade.

Clinically significant (CS) abnormal laboratory tests must be followed up as described in the protocol.

Did the subject develop any sign or symptom of severe malaria?

If Yes, the subject withdrawn from trial.

If Pregnancy test is “positive” complete ‘Notification of Pregnancy’ report

Reminders Exclude the subject if QTc interval >450msec. Use Fridericia’s formula to calculate QTc Please Exclude the Subject if weight is less than 35 kg.