Clinical Trail Data Management

CDM is defined as the process of collection, cleaning, and management of subject data in compliance with regulatory standards.
A database must be accurate, secure, reliable and ready for analysis.
CDMS is the tool for clinical data management.
RESPONSIBILITES OF CDM
STUDY SET UP (15%) - this includes all the activities that are done before at the starting of the study.
STUDY CONDUCT (60%)- this starts once a subject enrollment begins or with first patient‘s first visit.
STUDY CLOSEOUT (25%) -the data is final and ready for statistical analysis.
CASE REPORT FORM
Types of CRF
PAPER CRF
e-CRF
Data entry is a process of entering or transferring data from case report form ( paper or image ) to clinical data management system (electronic storage ).
optical mark reading (OMR)
Data entry may be entirely manual or partly computerized using optical character recognition (OCR).
The three basic types of data entry system:
(a) Local data entry system - data entry is done on site
(b) Central data entry system - data entry is done at data management centre from the received CRFs;
(c) Web based data entry system - data entry is done through web (secure link) using internet connection.
DATA CLEANING
MANAGING ADR DATA
ADR data are collected from clinical trials and marketed products.
All ADR are reported to clinical data management system or safety system.
During clinical trials-ADR information is also received through CRF or EDC.
These information are stored in clinical data management database.
DATABASE LOCK PROCESS
Data manager – data is accurate and complete
Clinical project manager – site activities are complete
Medical monitor - data is medically accurate
Biostatistician - data is ready for evaluation and analysis.
Data manager asks for the database to be locked .
Done through the company’s IT department.
Once locked, no data can be changed.
Signed process for locking the database is placed in Trial Master File (TMF)
Data base closure (database lock): The database closure for the study is done to ensure no manipulation of study data during final analysis.
DATABASE LOCK/FREEZE is a TWO step process:-
The first step is often referred as SOFTLOCK or DATABASE FREEZE- occurs after all data cleaning, validation, and QC activities have been finalized.
The second step is called HARDLOCK or DATABASE LOCK –At this stage the database is handed over to statistics for data analysis.
DATA TRANSFER
Traditional Data Transfer
CRFs developed by sponsor and supplied to the site along with completion/instruction manual .
Use a black or blue ball point pen for permanency – and PRESS HARD.
At the time of a monitoring visit, CRFs are reviewed for adherence to
guidelines and verified against source documents by the Monitor.
During the monitoring visit, site staff make required corrections to CRFs
Verified/corrected CRFs are submitted to the sponsor, leaving a legible
copy of the CRF at the site.

1. CLINICAL TRAIL DATA MANAGEMENT PREPARED BY:- R.MALINI M.PHARMACY  PHARMACY PRACTICE 1

2. OVERVIEW OF CLINICAL DATA MANAGEMENT 2

3. CLINICAL TRAIL DATA MANAGEMENT 3

4. WHAT IS CLINICAL TRAIL DATA MANAGEMENT? CDM is defined as the process of collection, cleaning, and management of subject data in compliance with regulatory standards . A database must be accurate, secure, reliable and ready for analysis . OBJECTIVES OF CDM:- to provide high-quality data keep the number of errors and missing data as low as possible. gather maximum data for analysis. CDMS is the tool for clinical data management. 4

5. CLINICAL TRAIL DATA MANAGEMENT RESPONSIBILITES OF CDM STUDY SET UP (15%) - this includes all the activities that are done before at the starting of the study. STUDY CONDUCT (60%)- this starts once a subject enrollment begins or with first patient‘s first visit. STUDY CLOSEOUT (25%) - the data is final and ready for statistical analysis. 5

6. CASE REPORT FORM 6 Data Manager Database Administrator Database Programmer Clinical Data Associate

7. Case Report Form (CRF): A paper or electronic data collection document used in human research. It is a tool used to collect data on each study participant . Study protocol provides the detailed methodology for running the trial, the CRF provides the main day-to-day information. CRF should be clear, and easy to follow and complete . Types of CRF PAPER CRF e-CRF 7 CASE REPORT FORM

8. 8 WELL DESIGNED AND POORLY DESIGNED CRF

9. 9 PAPER CRF AND e-CRF

10. CRF TRACKING AND CORRECTIONS CRFs tracking : All CRFs should be tracked . CRFs are tracked to detect missing pages too. Check the quality and completeness of the documents. If corrections are necessary, make the change as follows: Draw one horizontal line through the error Insert the correct data Initial and date the change DO NOT ERASE, SCRIBBLE OUT, OR USE CORRECTION FLUID OR ANY OTHER MEANS WHICH COULD OBSCURE THE ORIGINAL ENTRY 10

11. DATA ENTRY Data entry is a process of entering or transferring data from case report form ( paper or image ) to clinical data management system ( electronic storage ). Data entry may take a form of direct computer entry by a person transferring data from paper-based CRFs into a computer database , using optical mark reading (OMR) Data entry may be entirely manual or partly computerized using optical character recognition (OCR). The three basic types of data entry system: (a) Local data entry system - data entry is done on site (b) Central data entry system - data entry is done at data management centre from the received CRFs; (c) Web based data entry system - data entry is done through web (secure link) using internet connection. 11

12. DATA CLEANING 12 Data cleaning : Process of detecting, diagnosing, and editing faulty data . Scrub for Duplicate data is coming from different sources or users, for any reason, submit their entry more than once . Scrub for Irrelevant Data Irrelevant data is the type of information that doesn’t have any formal errors but is just not useful for your project .  Scrub for Incorrect Data Incorrect data is often easy to spot , as it’s just illogical. Handle Missing Data Missing data is just unavoidable .

13. MANAGING LABORATORY 13 TYPES OF LABORATORY :- CENTRAL LABS:- Samples are collected from different sites (hospitals) and they are sent to one special laboratory which is called central lab ( sponsor assigned) for testing purpose . LOCAL LABS:- Local labs are the regular lab facilities that are available in the hospital or nearby location . Each site (hospital) will have their lab. Sample of the patients on a particular site will be analysed in lab in that particular hospital.

14. MANAGING ADR DATA 14 ADR data are collected from clinical trials and marketed products . All ADR are reported to clinical data management system or safety system . During clinical trials- ADR information is also received through CRF or EDC . These information are stored in clinical data management database .

15. DATA TRANSFER Traditional Data Transfer CRFs developed by sponsor and supplied to the site along with completion/instruction manual . Use a black or blue ball point pen for permanency – and PRESS HARD. At the time of a monitoring visit, CRFs are reviewed for adherence to guidelines and verified against source documents by the Monitor. During the monitoring visit, site staff make required corrections to CRFs Verified/corrected CRFs are submitted to the sponsor , leaving a legible copy of the CRF at the site. If data is not retrieved at the time of the monitoring visit, sponsor may Want the CRFs submitted via mail. 15 DATA TRANSFER eCRF PAPER CRF

16. DATA TRANSFER Sponsor enters the CRF data into a centralized database ( generally done by 2 separate individuals, called double data entry) and reviews the data for errors. If inconsistencies are found, the sponsor generates data queries (forms may vary slightly from sponsor to sponsor) and sends to the site. Site staff investigates these queries and responds to them either directly on the data query form or on the CRF . The data correction is then re-submitted t o the sponsor for entry into their database . 16

17. Electronic CRF (eCRF) Site records data to the electronic database. Data periodically electronically transmitted to Sponsor/CRO or in Sponsor database Review of data performed by in house CRAs Less frequent CRA visits Electronic queries generated and sent to site Database lock 17 Missing Data at Time of Transfer Missing data elements Source Document (SD) not supporting CRF CRF not supporting SD Referred to as: Discrepancies Queries Clarifications Identified by: Sponsor Database

18. DATABASE LOCK Data base closure (database lock): The database closure for the study is done to ensure no manipulation of study data during final analysis. DATABASE LOCK/FREEZE is a TWO step process:- The first step is often referred as SOFTLOCK or DATABASE FREEZE - occurs after all data cleaning, validation, and QC activities have been finalized. The second step is called HARDLOCK or DATABASE LOCK – At this stage the database is handed over to statistics for data analysis . 18

19. DATABASE LOCK PROCESS Before the lock , the following individuals sign indicating the database can be locked : Data manager – data is accurate and complete Clinical project manager – site activities are complete Medical monitor - data is medically accurate Biostatistician - data is ready for evaluation and analysis. Data manager asks for the database to be locked . Done through the company’s IT department. Once locked , no data can be changed. Signed process for locking the database is placed in Trial Master File (TMF) User access is turned off. 19

20. References 20 Textbook of clinical reaserch – by GURU PRASAD https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1198040/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326906/#!po=38.1579 Clinical Data Management - Sponsored by Center for Cancer Research National Cancer Institute https://youtu.be/WhGksOUyMP4 https://www.slideshare.net/MaheshKoppula2/clinical-data-management-58285393 https://www.slideshare.net/DivyaDabbeta/clinical-data-management-190218435 https://www.slideshare.net/DivyaDabbeta/clinical-data-management-190218435 https://lifepronow.com/2020/05/28/difference-between-the-central-lab-and-local-lab-in-clinical-research/ https://www.iteratorshq.com/blog/data-cleaning-in-5-easy-steps/ https://www.slideshare.net/KatalystHLS/data-management-plankatalyst-hls