Clinical Data Management: Best Practices and Key Considerations

Clinical data management (CDM) is a critical component of clinical research, involving the collection, processing, and analysis of data generated during clinical trials. Implementing best practices and considering key considerations is essential for ensuring data quality, integrity, and regulatory compliance. Here are some important considerations and best practices in clinical data management:

Data Standardization: Standardizing data collection and documentation across study sites is crucial for ensuring consistency and facilitating data analysis. Develop standardized data collection forms, case report forms (CRFs), and electronic data capture (EDC) systems that capture relevant data elements in a consistent manner.

Data Validation and Quality Control: Implement robust data validation procedures to ensure the accuracy and completeness of collected data. Conduct thorough quality control checks, including data validation checks, range checks, and consistency checks, to identify and resolve data discrepancies or errors.

Data Security and Privacy: Ensure data security and protect participant privacy by implementing appropriate measures such as data encryption, secure data transfer protocols, access controls, and adherence to applicable data protection regulations like GDPR or HIPAA.

Data Monitoring and Cleaning: Regularly monitor data collection processes to identify and address data discrepancies, missing data, or outliers. Implement data cleaning procedures to identify and resolve data errors, inconsistencies, and outliers that may impact the integrity and reliability of the study data.

Data Traceability and Audit Trail: Maintain a comprehensive audit trail that captures all changes and activities related to data entry, data modifications, and data review. This ensures data traceability and facilitates data validation and regulatory inspections.

Standard Operating Procedures (SOPs): Develop and adhere to well-defined SOPs for data management activities. SOPs should cover all aspects of data collection, processing, validation, cleaning, and archiving, ensuring consistency and adherence to regulatory requirements.

1. Welcome CLINICAL DATA MANAGEMENT: BEST PRACTICES AND KEY CONSIDERATIONS Chetana Menda Pharm. D 084/052023 10/18/2022 www.clinosol.com | follow us on social media @clinosolresearch 1

2. Index What is Clinical Data Management (CDM)? Stages of Clinical Data Management. Clinical Data Management Process. Phases in Clinical Data Management. Objectives of CDM. Conclusion. References. 10/18/2022 www.clinosol.com | follow us on social media @clinosolresearch 2

3. What is Clinical Data Management (CDM)? Clinical Data Management (CDM) is the part of clinical trail management that deals specifically with information that comes out of the trails. CDM is a critical phase of clinical research, which leads to the generation of high quality, reliable and statistically sound data from clinical trials. Clinical Data Management includes the entry, verification, validation and quality control of data gathered during the conduct of a clinical trial. CDM is involved in all aspects of processing the clinical data. It involves working with a range of computer applications, database systems to support collection, cleaning and management of clinical trial data. Review and approval of new drugs by Regulatory Boards is dependent upon the integrity off clinical trial data which is the core purpose of CDM. 10/18/2022 www.clinosol.com | follow us on social media @clinosolresearch 3

4. Stages Of Clinical Data Management Data Management begins with the Development of the data management plan and Design of the data capture instrument (e.g. the case report form), continues with Data collection and regular quality control procedures, The database cleaning, Locking and ends with analysis, archiving and write-up. 10/18/2022 www.clinosol.com | follow us on social media @clinosolresearch 4

5. CLNICAL DATA MANAGEMENT PROCESS 10/18/2022 www.clinosol.com | follow us on social media @clinosolresearch 5

6. Phases in Clinical Data Management STARTUP PHASE : Startup phase consists of activities like Case Report Form (CRF) creation and designing , Database designing and testing , Edit checks preparation and User Acceptance Testing (UAT) along with document preparation such as data management plan, CRF completion guidelines, data entry guidelines and data validation plan. 10/18/2022 www.clinosol.com | follow us on social media @clinosolresearch 6 PHASES OF CDM CONDUCT CLOSEOUT STARTUP

7. 1. CRF Designing: CRF designing have two types , Paper CRF and eCRF . Paper CRF will be prepared by CRF designer and send to site for review. Upon confirmation, Paper CRF will be designed in electronic data capture (EDC) for data management (DM) team for data capture. eCRF will be designed directly in the EDC by EDC Tech lead and CRF designer and site will have EDC access to review it. 2. Database Designing: Database designing is done by Database Programmer and EDC designer. Key points like Field length, dynamic forms, acceptable range, access level management will be designed as per the study requirement. CRF annotation plays a vital role in assigning the variables for each field. After Database designing is successful, DB Programmer will implement the condition as per Data Validation Specification (DVS) for queries to fire for out of range conditions. 10/18/2022 www.clinosol.com | follow us on social media @clinosolresearch 7

8. 3. Edit Checks Preparation : Edit checks are created by a database designer and embedded into eCRFs to automatically compare inputs against numerical and logical criteria. This prevents unlikely values from appearing in the document. 4. User Acceptance Testing(UAT) : User Acceptance Testing (UAT) is the process where edit checks with specific conditions as per protocol is created by the Clinical Data Analyst (CDA) and Clinical Database Programmer (CDP) creates those condition in the database to fire query for the conditions. Data validation Specification (DVS) is the document where CDA writes all the edit checks and CDP modifies the EDC as per DVS. Ex : As per protocol, Age Inclusion is 18 to 55 years : When the captured as below 18 or above 55, Query fires with Query text as “ As per protocol, Age Inclusion is 18 to 55 years, please confirm”. 10/18/2022 www.clinosol.com | follow us on social media @clinosolresearch 8

9. CONDUCT PHASE: Conduct phase is the longest and most critical phase where Data capture , Data Cleaning , Data reconciliation , Medical Coding and Data Validation takes place with regular evaluation of data known as Interim Analysis along with documentations such as Query Management Form, Revision Request Form, Post Production Changes. 1. Data Collection: In e-CRF, the clinical site will directly capture the data in EDC and confirm Source Data Verification which is the latest most welcoming method by sponsors to avoid discrepancies. 2. Discrepancy Management: Query Management is the major process in Discrepancy Management which helps to clean the data by system generated queries or manual queries. The four types of queries are: Open query, Answered query, Closed query, and Cancelled query. 10/18/2022 www.clinosol.com | follow us on social media @clinosolresearch 9

10. Open Query are queries which is open to DM or site which is not answered yet. Answered Query are queries which is either answered by DM or site but not closed yet. Closed Query are queries which are closed as per the confirmation from either DM team or clinical site. Cancelled Query are queries which is cancelled by the DM team which has many reasons such as misfiring query, query not required, or query raised manually by mistake. 3. Medical Coding: The medical coding for the study is done as per the project specific protocol requirement. The dictionaries used for a study are: Adverse Events: MedDRA (Medical Dictionary for Regulatory Authorities) Medications: WHODD (World Health Organization- Drug Dictionary) 10/18/2022 www.clinosol.com | follow us on social media @clinosolresearch 10

11. 4. Data Reconciliation: CDM data reconciliation is a data review process that compares unique identifiers in the EDC data such as subject number, visit, nominal time point, collection dates and collection times with the same data points in the electronic external data source datasets . CLOSE OUT PHASE: Close out phase is the success phases for Data Managers where all the clean data are frozen and locked. After the confirmation of locking all the data, it will be only in Read only mode. Finally, the Database will be locked, and all the documents are archived. 10/18/2022 www.clinosol.com | follow us on social media @clinosolresearch 11

12. Database Lock: Database lock is the final process in Clinical Data Management . After all the queries are actioned and all outstanding issues are resolved, the Final Clean Data is frozen either manually or by script to ensure the data is not edited further which means post freezing, data will be in Read only mode. Once all the data are frozen, The Database lock approval is sent to stakeholder and sponsors. The database will be successfully locked. Post Database lock, the data will be extracted by Statistical programmers for analysis and Data management team completes all further documentation and proceed for archival. 10/18/2022 www.clinosol.com | follow us on social media @clinosolresearch 12

13. Objectives Of CDM: CDM is a vital vehicle in Clinical trials to ensure: The integrity and quality of data being transferred from trial subjects to a database system. That the collected data is complete and accurate so the results are correct. That the trial database is complete and accurate, and a true representation of what took place in trial. That the trial database is sufficiently clean to support statistical analysis, and its subsequent presentation and interpretation. 10/18/2022 www.clinosol.com | follow us on social media @clinosolresearch 13

14. Conclusion Clinical Data Management helps the pharmaceutical companies to speed up the drug development process by providing clean, high quality and reliable data which helps to submit relevant documents with strong support for the drug to regulatory authorities. “The mission of CDM is Consistency, Accuracy, Validity and Archiving the Data”. 10/18/2022 www.clinosol.com | follow us on social media @clinosolresearch 14

15. References https://www.slideshare.net/KatalystHLS/clinical-data-management-process-overviewkatalyst-hls https://www.slideshare.net/finenessinstitute/understanding-clinical-data-management https://www.smartsheet.com/content/clinical-trial-data-management-guide https://ijshr.com/IJSHR_Vol.4_Issue.4_Oct2019/IJSHR0013.pdf 10/18/2022 www.clinosol.com | follow us on social media @clinosolresearch 15

16. Thank You! www.clinosol.com (India | Canada) 9121151622/623/624 [email protected] 10/18/2022 www.clinosol.com | follow us on social media @clinosolresearch 16