CRF designdsgcp.dk/inc/uploads/2016/04/GCP_create_CRF.pdf · - Query handling - Perform medical...

07-10-2015 BioStata, Bregnerødvej 132A, Birkerød

CRF design


Clinical Protocol:

- Primary endpoints

- Secondary endpoints

- Safety

- Monitoring fields

- Other

Its all data!

Creating a CRF - protocol


Locate what to be reported in CRF

....... sometimes hard to find.

Creating a CRF - protocol


Creating a CRF

eCRF

SOPs

CRF Standards- Internal- CDISC stnd.

Data Base requirements

Input from Study team

Authorities/GCP/FDA

SAP (Statistical Analysis

Report)


CDISC standards (CDASH)

The Clinical Data Acquisition Standards Harmonization (CDASH) Standard defines basic standards for the collection of clinical trial data.

- Best Practice Recommendations for CRF design

- Alligned with SDTM (data submitted to e.g. FDA)

CDASH CRF SDTM

e.g. a date: 19-Jun-2012 16:00 2012-06-19T16:00

Creating a CRF – international CRF stnd.


Creating a CRF – input from study team

Data Management CRF design

statistician

Medical Coder

Trial Manager

/CRA

SiteSDTM

programmer

Sponsor

Medical writer


Statistician: - SAP

- Focus on endpoints

- Data to be reported

Medical Writer: - Data to be reported

Trial Manager/: - Protocol covered

CRA - Site ”point of view”. E.g. Sequence, help text

Programmer: - CDISC formats and standards

Site staff: ?

Medical coder: - Possible to code in MedDRA/WHOdrug

- E.g. conc. medication: route and preferable dose should be present

Creating a CRF - input


Example: field for Date and time of handing out Diaries to subject

Statistician: Not to be analyzed and reported. Don’t collect!

Trial Manager/CRA: Nice to have. Possible to check date against e.g. visit date?

Programmer: Enter CDISC-ISO 8601 format: 2012-06-19T16:00

Site staff: Free text field so we can enter what patient says e.g.: “Last Sunday around 5ish”

Data Manager: - Need or nice to have? - Fit to database?- Easy to “use” -> avoiding queries

Creating a CRF - input


- Avoid redundant data

- Avoid ”nice to have data”

- Avoid free-text fields

- Focus on data needed- data needed to answer the protocol questions - provide adequate safety and efficacy data

Keep CRF simple and logical

Creating a CRF – data to collect


- From a users view?

- From a Data Managers view?

- From statisticans view?

What is eCRF data ?


Example of an eCRF form (AE)- from a user view


Example of an eCRF form (AE)- from a DM view


Example of eCRF data (AE)- from a programmer or statistican view


- Edit checks (automatic generating of queries)

eCRF - queries


Field appears depended on answer

eCRF – Dynamics- fields appears during entry


SAE ‘actions’ depended on answer

eCRF – Dynamics- adding sections and e-mail alerts


SAE= ”yes”



SAE= ”yes”

E-mail Alert



If subject is a Screening failure, the remaining sections/visits in CRF should ne be filled in -< removed.

eCRF – Dynamics- removing CRF pages or sections


- Data Validation plan

- eCRF Completion guide

- Quality Check of eCRF, database, features

- CRF Annotation

- Training of users

eCRF- supporting documentation and processes


- Data Validation plan

- programming of and UAT of checksExample of a Validation Plan

CRF - Data Validation plan


Instruction to site staff on how to operate the eCRF and system

- Login

- Change psw

- Create subject

- Enter data

- Change data

- Handle queries

- Help needed

- etc.

CRF - eCRF Completion Guide


We need to prove that CRF setup, queries, dynamics, reports etc. works as intended !

- Check all entry fields

- Check all queries hits as intended and do not hit if not intended

- Check data extractions from CRF

- Etc..

- Document!

eCRF –Quality Check of CRF and database setup


Example of an User Acceptance test script

- step-by-step though the CRF

CRF –Quality Check of CRF and database setup


Document describing mapping between CRF and data in database

CRF- Annotation


Training of users:

- Different roles – different training

DM trains CRA/Trial Managers

CRA/Trial Managers trains Site staff

CRF – Training of users


eCRF go live !

CRF


Data Management tasks


- Review protocol

- Design the CRF- Set-up the database- Design data entry screens- Test CRF and database

- Write a Data Handling Protocol (how will DM be handled)

- Write a data validation plan

- Program data checks according to validation plan and test

- Handle external data vendors (e.g. laboratories)

- Training

Data Management tasks


- Validate data during study

- Query handling

- Perform medical coding (MedDRA and WHODrug)

- Perform SAE reconciliation

- Prepare a Data Handling Report

- Release Data for analysis

- Data Base lock

- Host Data Base Release meeting

Data Management tasks, continued


Reports in Data Management

Data Handling Protocol

Table of Contents:

1 Study team…………………………………………. 3

2 Timelines………………………… ………………….3

3 Scope of Laboratory data…………………………. 4

4 Handling and archiving of source documents……5

5 Data Entry………………………………………….. 6

5.1 Description of data entry (and comparison)…….. 6

5.2 Query handling…………………………………….. 6

6 Electronically transferred laboratory data……….. 7

7 Database…………………………………………….8

7.1 Transfer of database………………………………. 8

8 Reconciliation of Serious Adverse Events (SAE). 8

9 Data Validation……………………………………...8

Appendices:

Appendix A: Annotated CRF

Appendix B: Format description of laboratory data (elect. transferred)

Appendix C: Data entry Guideline

Appendix D: Validation Plan

Appendix E: Approval of Data Handling Protocol

Data Handling Report

Table of Contents:

1 Sign-off Form (test of data entry screens)………........................... …3

2 Data Entry………………………………………….. …………………….4

2.1 Decisions during data entry………………………. …………………….4

3 Queries……………………………………………… …………………….4

4 Database Release Documentation………………. …………………….4

4.1 Table of screened, randomized, completed and withdrawn subjects..4

4.2 Data Validation…………………………………….. ……………………..5

4.3 Protocol Violations…………………………………. ……………………..5

4.4 SAE Reconciliation………………………………… ……………………..5

5 Deviations from Data Handling Protocol………… ……………………..5

6 Changes to the Database after Database Release………..…………..5

7 Quality Control of the Database………………………………………….5

8 Data Load Logs ……………………………………………………………6

8.1 Lab data transfer from external partners to BioStata ………………….6

8.2 Data transfer from BioStata…………………….…………………………6

Appendices:

Appendix A: Sign-off Form (test of data entry screens)

Appendix B: Final Validation Output

Appendix C: Database Release Minutes

Appendix D: Database Release Approval Form

Appendix E: Approval Form of Data Handling Report


Non-CRF study data e.g.:

- Laboratory data

- ECG central reading

- PK

- Images central reading

Data from external partners


Example of a record (laboratory data):

||402804||SCREENING|0|19010101||BIOCHEMISTRY|BIOCHEMISTRY|BIOC|LAB_TEST|SAMPLE_ID|0|1|219||BATCH DATA LOAD|"XXX"

||402804||SCREENING|0|19010101||BIOCHEMISTRY|BIOCHEMISTRY|BIOC|LAB_TEST|LPARM_CODE|0|1|S-SODIUM||BATCH DATA LOAD|"XXX"

||402804||SCREENING|0|19010101||BIOCHEMISTRY|BIOCHEMISTRY|BIOC|LAB_TEST|LVALUE|0|1|138||BATCH DATA LOAD|"XXX"

||402804||SCREENING|0|19010101||BIOCHEMISTRY|BIOCHEMISTRY|BIOC|LAB_TEST|LPARM_UNIT|0|1|MMOL/L||BATCH DATA LOAD|"XXX"

||402804||SCREENING|0|19010101||BIOCHEMISTRY|BIOCHEMISTRY|BIOC|LAB_TEST|RETESTSN |0|1|1||BATCH DATA LOAD|"XXX"

||402804||SCREENING|0|19010101||BIOCHEMISTRY|BIOCHEMISTRY|BIOC|LAB_TEST|BIRTH_DATE|0|1|19530710||BATCH DATA LOAD|"XXX"

||402804||SCREENING|0|19010101||BIOCHEMISTRY|BIOCHEMISTRY|BIOC|LAB_TEST|SEX_CODE|0|1|Male||BATCH DATA LOAD|"XXX"

||402804||SCREENING|0|19010101||BIOCHEMISTRY|BIOCHEMISTRY|BIOC|LAB_TEST|COLLECTION_DATE|0|1|20051210||BATCH DATA LOAD|"XXX"

||402804||SCREENING|0|19010101||BIOCHEMISTRY|BIOCHEMISTRY|BIOC|LAB_TEST|COLLECTION_TIME|0|1|151047||BATCH DATA LOAD|"XXX"

||402804||SCREENING|0|19010101||BIOCHEMISTRY|BIOCHEMISTRY|BIOC|LAB_TEST|TEST_MEDIUM_CODE|0|1|SERUM||BATCH DATA LOAD|"XXX"

||402804||SCREENING|0|19010101||BIOCHEMISTRY|BIOCHEMISTRY|BIOC|LAB_TEST|NOMINAL_TIME_CODE|0|1|12||BATCH DATA LOAD|"XXX"

||402804||SCREENING|0|19010101||BIOCHEMISTRY|BIOCHEMISTRY|BIOC|LAB_TEST|NOMINAL_TIME_UNIT|0|1|Hours||BATCH DATA LOAD|"XXX"

||402804||SCREENING|0|19010101||BIOCHEMISTRY|BIOCHEMISTRY|BIOC|LAB_TEST|COMMENT_TEXT|0|1|SAMPLE MISSING||BATCH DATA LOAD|"XXX"

||402804||SCREENING|0|19010101||BIOCHEMISTRY|BIOCHEMISTRY|BIOC|LAB_TEST|REF_RANGE_YN|0|1|Yes||BATCH DATA LOAD|"XXX"

||402804||SCREENING|0|19010101||BIOCHEMISTRY|BIOCHEMISTRY|BIOC|LAB_TEST|REF_FLAG_HL_CODE|0|1|High||BATCH DATA LOAD|"XXX"

||402804||SCREENING|0|19010101||BIOCHEMISTRY|BIOCHEMISTRY|BIOC|LAB_TEST|CLIN_SIG_YN|0|1|No||BATCH DATA LOAD|"XXX"

||402804||SCREENING|0|19010101||BIOCHEMISTRY|BIOCHEMISTRY|BIOC|LAB_TEST|REF_LOW_VALUE|0|1|80||BATCH DATA LOAD|"XXX"

||402804||SCREENING|0|19010101||BIOCHEMISTRY|BIOCHEMISTRY|BIOC|LAB_TEST|REF_HIGH_VALUE|0|1|134||BATCH DATA LOAD|"XXX"



Data from external partners- data flow

BioStataeCRF

SitesLab.

Samples

BioStataLab data

Lab. analyse result data

Reconcile

Queries

CRF data Querie

s

Lab 2

Lab 3


Data Transfer

Specification



- All data in database (incl. External data)

- All data cleaned (queries resolved)

- All medical terms coded (e.g. AE’s, Concom. Med)

- etc.

Data Base (soft) Lock (data cannot be changed)

Data Base Lock and release


- Data Reviewed by study team

- SAP approved

- Subject classification

- Etc.

Data Base Release

Data Base Lock and release, continued


- Data Base Released

- Unblinding

- Reports finalized

- All acceses to eCRF removed

Data Base (hard) Locked

eCRF and data are not available anymore



Data base unlock (if changes to data are needed)

- ‘DB unlock form’ to be issued

- Data to be changed

- Reason for unlocking

- Actual changes to data must be documented

- Data needs to be re-validated

- Documentation that no other data is changed

- New Data Base Release form to be approved

- Relevant persons must be informed



?

Thank you for your attention.

Kenneth Bø[email protected]: +45 2774

8207

mailto:[email protected]

CRF designdsgcp.dk/inc/uploads/2016/04/GCP_create_CRF.pdf · - Query handling - Perform medical...

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