Clinical Data Management-An Introduction : Clinical Data Management-An Introduction What is Clinical Data Management : What is Clinical Data Management Clinical Data Management is involved in all aspects of processing the clinical data, working with a range of computer applications, database systems to support collection, cleaning and management of subject or trial data. Slide 3: 3 Clinical Data Management is the collection,
integration and validation of clinical trial data
During the clinical trial, the investigators collect data on the patients' health for a defined time period. This data is sent to the trial sponsor, who then analyzes the pooled data using statistical analysis. Clinical Trial Data Why CDM : Why CDM Review & approval of new drugs by Regulatory Agencies is dependent upon a trust that clinical trials data presented are of sufficient integrity to ensure confidence in results & conclusions presented by pharma company
Important to obtaining that trust is adherence to quality standards & practices
Hence companies must assure that all staff involved in the clinical research are trained & qualified to perform data management tasks Key members : Key members The Key members involved in Data Management:
Clinical Data Manager
Clinical Data Coordinator
Clinical Data Associate Slide 6: Bigger Picture Slide 7: Clinical Trail Overview Slide 8: 8 Clinical Investigator
Clinical Research Manager/Associate
Monitor Regulatory affairs
Clinical Data Management
Clinical Safety Surveillance Associate (SSA)
Auditor/Compliance Multidisciplinary Teams in Clinical Trials Responsibilities of CDM : Responsibilities of CDM Study Setup
CRF design and development (paper/e-CRF)
Database built and testing
Edit Checks preparation and testing Study Conduct
Data Coding (using MEDRA and WHODD dictionaries)
Data review (Ongoing QC)
Data Transfer Study Closeout
Database Transfer Slide 10: 10 Slide 11: 11 CRF Design/Review : CRF Design/Review A representation of the study as outlined in the protocol is made (including CRF completion guidelines if necessary). Therefore a final protocol needs to be available before this activity can be initiated.. CRF design usually takes about three rounds: First draft (rough without detail but correct content), second draft (as good as we can get it) and final version. We need input from our sponsor to correct draft versions and to approve the final version.
Traditional Paper Based Case Report Forms
e-CRF (Electronic Case Report Form)- Study information directly entered into computer.
e-CRF is prepared by using:
CLINTRIAL Slide 13: Paper CRF e-CRF How many CRFs do you need? : How many CRFs do you need? Eligibility or Screening form
Physical Exam form
Medical History form
AE form/ SAE form
Concomitant therapy form
Blood test form
Laboratory test form
Follow-up Visit form Data Base Design : Data Base Design Data from a clinical trial will be collected and stored in some kind of computer system.
A database is simply a structured set of data.
A collection of rows and columns.
--Oracle application DBMS:MS Access XP, MS Excel XPOracle ClinicalClintrialPhaseforward InFormmedidata Rave : DBMS:MS Access XP, MS Excel XPOracle ClinicalClintrialPhaseforward InFormmedidata Rave CRF Annotation : CRF Annotation An annotated CRF is generally defined as a blank CRF with markings, or annotations, that coordinate each data point in the form with its corresponding dataset name.
Essentially, an annotated CRF communicates where the data collected for each question is stored in the database.
CRF Annotation is the first step in translating the CRFs into a database application.
CDM annotates the CRFs by establishing variable names for each item to be entered.
Reviewed by CDM and Statistician Validation Checklist: : Validation Checklist: Validation Checklist describes in detail which data shall be checked and queried if necessary. The programming of the checks occurs according to this checklist. Before the programming starts, the sponsor will be asked to give approval of this Validation Checklist.
Test subjects are entered in the database to test the entry screens and the programming. The exact number of test subjects is not standard, but every check has to pass and fail (negative and positive proof) at least once. Database set up and testing : Database set up and testing Database setup and testing are always performed in a secure, non study data environment. Only when a database has been reviewed and fully tested, will it be set in ‘production’, a separate environment where only study data will be entered. Changes in structure or programming will always first be performed and tested in the non study data environment before they are made effective in the ‘production’ database. Slide 22: 22 CRF Tracking : CRF Tracking Logistic way if it is paper based study.
EDC-electronic data capture if it is e-CRF.
Data entry is a process of entering/transferring data from case report form to Clinical Data Management System (CDMS).
Data Entry: 1) Single data Entry
2) Double Data Entry Discrepancy Management : Discrepancy Management Discrepancy management is a process of cleaning subject data in the Clinical Data Management System (CDMS), it includes manual checks and programmed checks. Trivial discrepancies are closed as per self evident correction method or Universal ruling and discrepancies which require response from the site are queried by raising Data Clarification Forms (DCF). Medical Coding : Medical Coding The medical coding for a study is done as per the project specific protocol requirement. The dictionaries used for a study are:
Adverse Events: MedDRA (Medical Dictionary for Regulatory Activities)
Medications: WHODD (World Health Organization – Drug Dictionary)
Manual coding is performed using Thesaurus Management System (TMS) which is integrated with our Clinical Data Management System (CDMS). SAE Reconciliation : SAE Reconciliation Serious Adverse Event (SAE) data reconciliation is the comparison of key safety data variables between Clinical Data Management System (CDMS) and Master Drug Safety Database (MDSD). Reconciliation is performed to ensure that events residing in both systems are consistent. Slide 27: 27 Quality Control : Quality Control Quality Should be maintained for overall study by performing Quality checks at intervals for all data points (Critical & Non-Critical) prior to database lock.
QC helps to ensure that all the data processed is accurate, clean and Correct. Database Lock : Database Lock The database lock for a study is done to ensure no manipulation of study data during the final analysis.
Database lock for a study is done once all data management activities are completed. This includes the database lock checklist which ensures the same. Some of the activities included in database lock checklist are All discrepancies closed, DCFs received and updated, coding complete, SAE Reconciliation process complete etc. Slide 30: 30 Slide 31: 31 CDM is a vital vehicle in Clinical Trials to ensure:
The Integrity & quality of data being transferred from trial subjects to a database system
That the collected data is complete and accurate so that results are correct
That trial database is complete and accurate, and a true representation of what took place in trial
That trial database is sufficiently clean to support statistical analysis, and its subsequent presentation and interpretation Objectives of CDM Slide 32: 32 CDM has evolved from a mere data entry process to a much diverse process today
It provides data and database in a usable format in a timely manner
It ensures clean data and a ‘ready to lock’ database Importance of CDM Slide 33: 33 CDM Professionals:
Graduates/Post graduates in Life Sciences, IT, Statistics
Graduates with post graduation diploma in Clinical Research
Licensed Medical Practitioners
ICH.E188.8.131.52: Utilize qualified individuals to:
Supervise overall conduct of trial (Project Manager)
To handle and verify the data (Data Manager)
To conduct the statistical analysis (Biostatistician)
To prepare study reports (Medical Writer) CDM Professionals Slide 34: 34 Data Management Role in Clinical Research: DM Role in Clinical Research The data management function provides all data collection and data validation for a clinical trial program
Data management is essential to the overall clinical research function, as its key deliverable is the data to support the submission
Assuring the overall accuracy and integrity of the clinical trial data is the core business of the data management function Continued… Slide 35: 35 Data management starts with the creation of the study protocol
At the study level, data management ends when the database is locked and the Clinical Study Report is final
At the compound level (of the drug), data management ends when the submission package is assembled and complete DM Role in Clinical Research Mission of CDM : Mission of CDM Consistency
Archiving Slide 37: DATA MANAGEMENT WORKFLOW Receipt of CRFs
(CRF Tracking/Filing) First Pass Entry Second Pass Entry Clinical Data Management Batch Validation Thesaurus Manual Coding Discrepancy Management DCF Resolutions SAE Reconciliation Quality Control Plan Database Lock Auto Coding Electronic Archival Data ClarificationForm