CRF Design & Utilization - UKM Medical Centre

CRF Design & Utilization 

GCP Course 

Pusat Perubatan UKM 

Kuala Lumpur 

T Mahendran 

Consultant, Medical Affairs 

SS Inter Pharma Consultants 

Kuala Lumpur, Malaysia 

T Mahendran/CRF Design & Utilization 

29/11/2011 1

ICH GCP 

• 8 Sections covering the 

• principal participants 

and responsibilities 

• ethics committees 

• investigator 

• sponsor incl. monitor 

• principal procedures 

• designing 

• conducting 

• recording 

• reporting 

of clinical 

studies 

• main paperwork 

• main terms 

• clinical study protocol 

• investigator’s brochure 

• clinical study report 

• essential documents 

glossary including 62 terms from 

adverse drug reaction to wellbeing 

of trial subjects 


29/11/2011 2

Case Report Forms (CRF) Design 


29/11/2011 3

What‟s A CRF? 

A Case Report Form (or CRF) is the tool 

used to collect data; it can be a paper- or 

electronic-based questionnaire specifically 

used in a clinical trial/research. 


29/11/2011 4

Purpose of the CRF 

• Collection of relevant data in a specific format 

• As per protocol 

• In compliance with all regulatory requirements 

• Allows for efficient and complete data processing, 

analysis and reporting 

• Facilitates the exchange of data across projects and 

organizations esp. through standardization 

T Mahendran/CRF Design & Utilization

Relationship of CRF to Protocol 

• Protocol determines what data should 

be collected in the CRF 

• All data specified in the protocol must 

be collected in the CRF 

• Data that will not be analyzed should 

not appear in the CRF 


CRF Design & Development Process 

Involvement of all Stakeholders 

• Project Clinician/Medical Director 

• Clinical Research Associate (CRA) 

• Statistician 

• Database Programmer 

• Data Manager 

• Others 

• Standards, Dictionary Coding, 


Poorly Designed CRFs 

• Garbage In = Garbage Out 

• Data not collected 

• Database may require modification 

• Need to edit data 

• Target dates are missed 

• Over-collection of (irrelevant) data – 

resources wasted in collecting & processing 


CRF Design Overview 

in Industry 

• Harmonization of recording patient data 

• Process of creating CRFs 

• CRF layout 

• General structure 

• Individual modules (building blocks of CRF) 


29/11/2011 9

Harmonized CRF Modules 

acc. to Sponsor Standards 

Standard Templates exist for the following CRF Modules: 

• Informed Consent (incl. Contraception/Pregnancy) 

• Demographic Data 

• Physical Examination 

• Vital Signs/ECG 

• Medical History 

• Laboratory/Urinalysis 

• Adverse Events 

• Concomitant Medication 

• Study Medication 

• Termination Section 


29/11/2011 10

CRF Design 

• Harmonization (bringing in agreement) of 

individual components of CRF 

= agreement on systematic way of asking 

for patient data 

• Use of standard templates and modules 

• Design-Tool: QuarkXPress (a professional 

layout all program) 


29/11/2011 11

Path from 

study 

information 

(protocol) to 

printed CRF 


29/11/2011 12

Protocol 

CRF-Design 

5 days 

CRF Design & Review 

Timelines 

CRF-Design + 

Data Management 

5 days 

Delivery 

1st Draft * 

Final 

Working 

Draft * 

Final 

Draft for 

Proof 

Printing 

Proof 

Print 

Final 

Print 

CRF Development 


29/11/2011 13

Overview 

Cover and Spine 

(Pantoprazole) 

cover and spine 

layout version of 

licenced product 

- phase IV study 

Confidentiality 

Barcode 

on all NCR pages for 

scanning of pages 


29/11/2011 14

Layout of CRF-Pages 


29/11/2011 15

Study Schedule/ 

Overview 

‣ Time-saving quick 

reference 

‣ Outlines all study 

specific procedures 

‣ Indicates what to be 

done at which visit 


29/11/2011 16

Order of Sections 

General Structure of CRFs 

Visits (e.g. B0 – T12, V0 – V4) 

Medical History 

Planned Surgeries 

Adverse Events 

Concomitant Medication 

Study Medication 

Termination Section 

Serious Adverse Event Reporting Form 


29/11/2011 17

CRF Contents 


29/11/2011 18

Informed Consent / In-/Exclusion Criteria 

First of all.... 

Patient IC 

Inclusion 

criteria 

Exclusion 

criteria 


29/11/2011 19

Demographic Data 

• Date of birth 

• Gender 

• Height 

• Weight 

• Race Asian 

Black 

White 

Other 

• Smoking 


29/11/2011 20

Physical Examination 

(Initial Visit / Termination Visit) 


29/11/2011 21

Changes in Medication / AE 

T4 

CM 

AE 

SM 

AE 


29/11/2011 22

Medical History 

• Study indication (e.g. asthma) 

preprinted, if applicable 

• Definition of "relevant previous" 

is study specific 

• Please check with section 

"Planned surgeries" because the 

underlying disease/diagnosis has 

to be entered here. 

• In case a diagnosis is deleted, 

please don't renumber. 

Reason: link to CM 


29/11/2011 23

Planned Surgeries / Invasive Procedures 

Enter name 

of planned 

surgery / 

procedure 

Enter actual 

date of event 

(or tick if not 

performed) 


29/11/2011 24

Adverse Events 

• Do not change the number of the AE 

• Please enter one diagnosis. If no 

diagnosis is available but only 

symptoms, for each symptom a 

separate AE form has to be filled in 

(e.g. nausea and vomiting) 

Reason: only one symptom can be 

coded. 

• Final outcome "unknown", please 

check, when collecting the CRFs 


• Don't forget the mandatory comment 

on causality assessment. 

29/11/2011 25

Relevant Previous and Concomitant Medication 

MH 

AE 


29/11/2011 26

Study Medication 

• Study specific form 

• Mandatory: 

- Study medication (preprinted) 

- Start date 

- Stop date 

• Optional: 

- Study Period 

- Recording of returned medication 

- Dosage (frequency, strength) 


29/11/2011 27

Section T 

Extended by central 

safety tests (Laboratory 

test, ECG etc.) 

Premature discontinuation: 

Mandatory and optional reasons 


29/11/2011 28

Case Report Form (CRF) Utilization 


29/11/2011 29

ICH GCP 

• 8 Sections covering the 

• principal participants 

and responsibilities 

• ethics committees 

• investigator 

• sponsor incl. monitor 

• principal procedures 

• designing 

• conducting 

• recording 

• reporting 

of clinical 

studies 

• main paperwork 

• main terms 

• clinical study protocol 

• investigator’s brochure 

• clinical study report 

• essential documents 

glossary including 62 terms from 

adverse drug reaction to wellbeing 

of trial subjects 


29/11/2011 30

General Completion Instructions 


29/11/2011 31

Baseline visit B0 

• Informed 

consent 

has to be 

available 

• Inclusion/ 

exclusion 

criteria 

check 


29/11/2011 32


No initials will be 

recorded in the 

CRF ! 


29/11/2011 33


No entry 

necessary if 

„Others‟ is 

without findings 

No ECG entry! 


29/11/2011 34


Enter “Not Known” 

(NK) if data not 

available 


29/11/2011 35

Baseline visit B0 (B1 – B4) 

Within 1.5 h vs. 

anticipated time of T0 

Multiply predicted value acc. 

to Quanjer table with factor 

0.9 (if patient is non-european 

or non-caucasian) 


29/11/2011 36


verification of 

B0 lab results, 

if applicable 


29/11/2011 37

Baseline visit B1 (B2, B3, B4) 

x 

x 

Randomization 

criteria fulfilled 

=> go to T0 

x 


29/11/2011 38

Treatment visit T0 

Baseline period >2 weeks: 

Laboratory test 

Urinalysis 


29/11/2011 39

Medical history 

Diagnoses/ 

diseases in the 

last 6 months 

prior to B0 


29/11/2011 40

Adverse events 

„yes‟ or „no‟ 

to be ticked 

Final outcome 

to be entered 

also for FU 

Causality assessment 

should be given in any case! 


29/11/2011 41

Concomitant Medication 

Combination 

drugs – only trade 

names! 

Formulations as 

exact as possible 

Rescue 

medication 

(salbutamol) 

to be recorded 

only once 


Strength of smallest unit 

29/11/2011 42

Study termination/Discontinuation report 

includes: 

• Physical examination 

• Vital signs 

• ECG 

• Laboratory investigations (no urinalysis) 


29/11/2011 43

Study termination/Discontinuation report 

Please check protocol 

for discontinuation criteria 

(chapter 13.1) 

Sign & date after 

last study-related 

activity 


29/11/2011 44

Thank you for your attention! 

~~~ Questions ~~~ 


29/11/2011 45

CRF Design & Utilization - UKM Medical Centre

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