Data Management in CT

7/30/2019 Data Management in CT

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Drug Development Life Cycle

5,000 –10,000Screened

250Enter Preclinical

Testing

5Enter

ClinicalTesting

1Approvedby theFDA

Net Cost: $ 1 Billioninvested over 15 years

16

14

12

10

8

6

4

2

0Discovery(2-10 Years)

Preclinical TestingLaboratory and

Animal Testing

Years

Phase I20-80 Healthy VolunteersUsed to Determine Safety

And Dosage

Phase III1,000-5,000 Patient Volunteers Used to

Monitor Adverse Reactionsto Long-term Use

Phase II100-300 Patient VolunteersUsed to Look for Efficacyand Side Effects

FDA Review/Approval Additional

Post-marketingTesting

Compound Success Rates by Stage

Source: Tufts Center for the Study of Drug Development

Drug development is a r isky and expensive proposi t ion



The design and conduct of GCP compliant

clinical trial is a hugely complex undertaking, notto mention an expensive one. It requires many

professionals from diverse disciplines to perform

the variety of work processes entailed.

Prologue





Clinical Data Management

• Clinical Data Management is the techno logy and

processes that manage cl in ical data to produce a

hig h quali ty, clean and analyzable database.



Clinical Data Management is a key

business process in drug discovery lifecycle

and key to drastic reduction in time from

development to market for all phases of clinical research.



Why is CDM Important ?

To provide consistent, accurate & valid clinicaldata

To support the accuracy of the final conclusion &

report To ensure the integrity and quality of data being

transferred from trial subjects to a database

system

To support the statistical analysis, and its

subsequent presentation and interpretation of the

trial report



ICH (International Conference on Harmonization) GCP (Good Clinical Practices )

GLP (Good Laboratory Practices)

GMP (Good Manufacturing Practices)

FDA (Food & Drug Administration)

EMEA (European agency for Evaluation of Medicine)

IRB (Institutional Review Board)

EC (Ethics Committee)

DCGI (Drug Controller General of India)

Regulatory Bodies



Guidelines…..

All clinical research data should be recorded, handled,

and stored in a way that allows its accurate reporting,

interpretation and verification. (ICH GCP 2.10, 4.9, 5.5,

5.14 and ICH E9 3.6 and 5.8)

Systems with procedures that assure the quality of every

aspect of the research should be implemented. (GCP

2.13)



Quality assurance and quality control systems with written

standard operating procedures should be implemented

and maintained to ensure that research are conducted

and data are generated, documented and recorded, and

reported in compliance with the protocol, GCP and

applicable regulatory requirements. (GCP 5.1.1)



More ICH Rules..

Data definition and processing

If data are transformed during processing, it shouldalways be possible to compare the original data andobservations with the processed data (ICH GCP 5.5.4)

Protocol amendments that necessitate a change in thedesign of the CRF, subject diaries, study worksheets, theresearch database and other key aspects of the CDMprocesses need to be controlled. (ICH E9 2.1.2)

Common standards should be adopted for a number of features of the research such as dictionaries of medicalterms, definition and timing of the main measurements,handling of protocol deviations. (ICH E9 2.1.1)



How does data flow?

Data Entry

(double)

Batch Validations

(Oracle Clinical)

DiscrepancyManagement

MedicalCoding

Tracking DCF

Resolutions

Data

CDMS

query

(DCF)

Case ReportForm (CRF)

Databaseupdates

Verbatimterms Manual

Coding

Database Lockand Data Transfer

SAEReconciliation

Safety Database

Quality controlProcedure

CRF Receipt,Tracking & Logging

Clinical sites

SITES CLINICAL DATA MANAGEMENT CENTER



P

r o t o c o l

D

e v e l o p m e n t

C

R F

D

e v e l o p m e n t

D

a t a A n a l y s i s P l a n

D

a t a E n t r y &

H

a n d l i n g S p e c s

C

R F R e v i e w

b y

F

i e l d M o n i t o r

D

a t a E n t r y

I T E d i t C h e c k

Q

u e r y G e n e r a t i o n

Q

u e r y

R

e s o l u t i o n / S D V

D

a t a b a s e L o c k

S

t a t i s t i c a l

A

n a l y s i s

DM DM DM DM DM

DM

CR CR CR CR CR

CR

ST ST

ST

ST

Data Management

Clinical Research

Statistical AnalysisOn-Site

CRF Review

In House Data Review

V

i s u a l R e v i e w

o f

D

a t a

CR

Protocol design and set-up

Data touches all …

DM DM



“Key Players” with Data Management

Project Data Manager

Lead Data Entry Associate

Data Entry Associates Data Coordinators

Medical Coder

Statistical Programmer

Biostatistician

Quality Associate

IT Engineer



Elements of Data Management

Data Management Plan –

CRF Processing/Filing

Data Entry Validation (Query Generation)

Query Management

Coding

Quality Checks Audits



CDMS

Database

CDM Activities

Trial Sites

SourceDocuments

Processes & Compliance

DataTracking

QueryManagement

SubmissionSystem Integration



Case Report Form ~ CRF

Examination Area Normal AbnormalComments

(If abnormal, comment required)

General Appearance

Skin

Lymph Nodes

H.E.E.N.N.T.

Chest and Lungs

Heart and peripheral

vasculature

Abdomen

Musculoskeletal

Gastrointestinal

Neurological

ABC Pharmaceuticals, Inc.

Protocol CL-H001

Screening No.

Subject Initials

Visit Date (dd MMM yyyy)

S c r e e n i n g V i s i t



Data Coding

Medical Dictionaries

MedDRA

Medical Dictionary for Regulatory Activities

WHO: WHOART, drugs World Health Organization Adverse Reaction

Terminology

ICD-10

International Classification of Diseases

COSTART

Coding Symbols for a Thesaurus of AdverseReaction Terms



Quality Checks

Should be applied to each stage of data handling to

ensure that all data are reliable and have been

processed correctly.

The Quality of overall data is increased because thesooner a data capture problem is detected & corrected,

the higher the quality of the final data

Setting up processes & systems to ensure that the dataare generated, documented (recorded), and reported in

compliance with (GCP) and applicable regulatory

requirement(s).



Audits

Independent

Participant folders

Comparison with database, tracking forms

Database

Comparison of data with CRFs

Queries

Are they all accounted for?

Are new values included in database?



Standards

Validation standards

FDA CFR 21-Part 11

Guidance for Computer Systems used in Clinical

Research Full ICH Guidelines compliance

The Clinical Data Interchange Standards Consortium(CDISC)

Compliance White papers



Data Management Systems -Technologies

ORACLE – Oracle Clinical

PHASE FORWARD – ClinTrial, Inform

MEDIDATA – Rave

DATA FAX

GO CRF

eTRIALS

Clinical Trial Setup CTS





Specifications for organizing study datasetsand their associated files in folders.





The Future (or is it present??)

EDC

Fax technology

Image based processing

Hand –held devices

Electronic Diaries

Optical Character Recognition

Others ….



Questions

