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clinical data manager

 CLINICAL DATA MANAGEMENT


Clinical data management (CDM) is a set of practices that handle information generated during medical research. It aims to ensure data quality, integrity, and compliance with internal protocols and state regulations.

Also, the CDM process helps keep key clinical trial stakeholders on the same page :

1. Sponsors — pharmaceutical companies, institutions, and other organizations that initiate, monitor, and finance the trial.

2. CROs (control research organizations)an organization contracted by another company to take the lead in managing that company's trials and complex medical testing responsibilities.

CRF design-Data manager             Database design-Database designer

Data capture-Data entry associate              Data validation-medical coder

Database lock-Quality control associate

Protocol review:reviewed done by the company team including data manager along with other team members

Protocol amendments :Changes procedure in document

Data management plan:

DMP should be developed for each study and early during the setup of the study

A data management plan or DMP is a document detailing all procedures, tasks, milestones, and deliverables throughout the CDM lifecycle. It gives a roadmap on how to work with information and handle possible risks. Another important function is to clearly communicate what happens in the course of the trial to each stakeholder.

INTRODUCTION

1.1 Purpose of the Data Management Plan (DMP)

1.2 Scope

2. SOPs

3. Data management Tasks

4. CORE/Primary project team members

5. Communication

5.1 Meetings

5.2 Status Reports/Metrics

6. clinical database used for project

7. Training

8. Data entry

8.1 Audit Trail

9. CRF Completion Guidelines

10. Clinical Database Design and Testing

10.1 Clinical Database Specifications

10.2 Clinical Database Development

10.3 User Acceptance Testing (UAT)

11. edit checks

11.1 System Checks

11.2 Manual Review

1. INTRODUCTION

1.1 Purpose of the Data Management Plan (DMP)

1.2 Scope

2. SOPs

3. Data management Tasks

4. CORE/Primary project team members

5. Communication

5.1 Meetings

5.2 Status Reports/Metrics

6. clinical database used for project

7. Training

8. Data entry

8.1 Audit Trail

9. CRF Completion Guidelines

10. Clinical Database Design and Testing

10.1 Clinical Database Specifications

10.2 Clinical Database Development

10.3 User Acceptance Testing (UAT)

11. edit checks

11.1 System Checks

11.2 Manual Review

11.3 Query Prefaces

12. Data flow

13. Medical Coding

14. SAE RECONciliation

15. Data IMPORT

15.1 Vendor Reconciliation

16. Data Export

17. Local Labs

17.1 Local Lab Data Entry

17.2 Local Lab Normal Ranges

18. Data Cuts

19. Interim Analysis

19.1 Data Cleaning Requirements

19.2 Post Analysis Unfreezing/Unlocking of data

20. quality control and database lock

20.1 Database Unlock

21. PROJECT DISPOSITION AND ARCHIVAL




The DMP typically describes the following aspects:

  • data to be gathered from trial participants,

  • existing data that can be integrated(how to mix,link,parts of  data)

  • data formats,

  • metadata and its standards,

  • storage and backup methods,

  • security measures to protect confidential information,

  • data quality procedures,

  • responsibility assignments across team members,

  • access and sharing mechanisms and limitations,

  • long-time archiving and preservation procedures,

  • the cost of data preparation and archiving, and

  • compliance with relevant regulations and requirement

  • Description of the data to be collected

  • Data storage & backup.

  • Data sharing & dissemination

  • Data security & confidentiality

  • Data preservation & archiving 

The DMP must be ready at a trial design stage, before the first participant is enrolled. This will ensure that data will be collected in the correct format and properly organized. However, the plan is not something immutable: It has to be updated across the trial, capturing any changes that influence data management.

STUDY START UP/STUDY SET UP:

eCRF(case report form):

The case report form is a printed or electronic questionnaire for collecting data from study participants and reporting it to trial sponsors. The document is created specifically for each research project in accordance with

  • the trial protocol, and

  • recommendations of the Clinical Data Acquisitions Standards Harmonization (CDASH). They are developed by Clinical Data Interchange Standards Consortium to streamline industry-wide data exchange. Say, CDASH dictates dd/mm/yy format for collecting dates. (Read our article on CDISC standards to learn more.)

Well-designed case report forms collect only data necessary for the particular study avoiding any redundancy. The fields to be filled in may include

  • demographics (age, gender),

  • basic measurements (height, weight),

  • vital signs (blood pressure, temperature, etc.) captured at various time points,

  • lab exams,

  • medical history,

  • adverse events, and

  • more, based on the research requirements.

Data managers create data entry screens and eCRF layouts in collaboration with a database programmer. The design usually goes through several review cycles before finalization.

  •  Crf pfd

  •  Compare crf pdf with protocol

  • eCRF specification-prepare

  • Explain ecrf spec to programmer

  • Draft ecrf Review,updates and changes

  • Final ecrf

  • Ecrf in EDC(electronic data management)

  • Compare ecrf spec with EDC

        EDIT CHECK DOCUMENT:  

                Edit check document

  • Edit check specification

  • Manual query and automated query

  • Dynamics 

  • Populate a query in edc

  • Provide edit check specification parallel with ecrf specification to programmer

  • Compare edit check specifications with edc

       UAT(user acceptance testing): 

  •  Role testing: testing role for team members like access

  • Screen testing

  • Structural functionality

  • Edit checks

  • Any of the data which falls out of range it should populate a query and for any thing which falls within a range that it express should not populate a query

  • LAB values-enter in UAT

  • Sponsor DM—CRO DM—LNR(lower normal range) template—Lead CRA(site)---Fill(template)---CRO CM—EDC —---manual,automated 

  • unticked

     eCRF completion guidelines

STUDY CONDUCT:

Patient —site—assessments–enter edc

Company project manager or clinical operation manager send SHIPPING MANIFEST to lab(vendor) – lab entry data in acquisition form

Lab—send test tubes—site

                                       |

                                       Pk samples–lab—analyze—send data to data manager

        Lab 2 types

  •  Central 

  •  Local 

CENTRAL:   Reference range values: lab maintain their own lab range values

Set  up:  acquisition form =site data in vendor database

LOCAL:  lab specific,site specific,sponsor specific

Set up:   they do not maintain acquisition form

         Data transfer specifications

  • unticked

     Version

  • unticked

    Table of contents

  • unticked

    Contact details

  • unticked

    Purpose

  • unticked

    Data file structure 

  • unticked

    Data file transfer

Frequency = weekly or monthly

Data transfers will be cumulative or incremental

Date of file

File naming conventions=blinded,unblinded


Data deliver method 

     email,sftp(secure file portal) like passwords or client web portal 

  • unticked

    Test transfer

  • unticked

    Data quality 

  • unticked

    Data receipt

  • unticked

    Data file contents

  • unticked

    Mapping tables =visit dates,codes

          Data transfers:

  • Mock data from vendors,IRT,SAE     

         Data transfer agreement:

       Purpose

       Type of data

         File naming conventions

         Data transfer mode 

         Data transfer type

         Frequency/Transfer frequency /schedule

  • Vendor agreements

  • Company agreements

Reconciliation :External data

  • Vendor reconciliation : reconcile lab data eg:Pk,ECG etc..

  • IRT reconciliation : reconcile header data eg:subjectid,site id etc…

  1. IRT=interactive response or randomization Technology

  2. IRT helps clinical trial sponsors & site for manage the patient & drug supply logistics—-->because =ability to offer control & flexibility while increasing efficiency

                                                                                                                                 

  1. IRT also helps to maintain blinding by making sure that specific roles in a study do not know the treatment that each patient is receiving

  2. CDM reconcile below list:                                                                                       

  • unticked

    Screening date

  • unticked

    Re-screening date

  • unticked

    Randomization number

  • SAE reconciliation:reconcile SAE data:

Adverse event : Any effect/disease

Adverse event maybe : MILD,MODERATE,SEVERE


Serious adverse event


  • unticked

    SAE →collected from→clinical trial & marketed products

  • unticked

    Reporting containing SAE —>case—->goes to safety department—>case of adverse effect

  • unticked

    During clinical trial=SAE information also received through CRF or EDC—>stored in ADVERSE EVENT—>DMS

  • unticked

    Stored in clinical & safety database

  • unticked

    Important to match = SAE with data management system—------->SAE reconciliation

              During information following information are checked:

  1. Cases found in the SAE system but not in the CDM system—->(case of adverse effect)safety system.  

  2. Cases found in the CDM system but not in the SAE system —>(adverse event)database system.

  • unticked

    Death —>any case—>found only one system–>.(cases of adverse effect) adverse event 

         Need of SAE reconciliation=compare SAE with CDM

   


SAE

CDM


Less organized/defined

more organized/defined

data: eg:

Subject & investigate ID

subject,investigate well defined in study data such as age, sex information


|

|


Collected information but collect only events

collected separately adverse event are collected event by event passociate each problem

                            Depends                                                                 for 

  • unticked

     Companies—---->reports & manual comparison—-->SAEreconclliation

                               On

  • unticked

    When the reporting system has access to the underlying database 

it might be possible to do

-------------------------------->

initial match on some information such as study ID,Sub ID etc…

    Underlying database present in SAE system and CDM system.




  • unticked

    SAE reconciliation-method              SAE            CDM

                |required                                        |                        |

                PLAN                               Data entered to create

                                                                      |

                                                   Two lists for direct comparison

                                                                      |then

                                  1)events in both lists are cross checks

                                  2)According to the plan,key data should  be 

                                     Compared in each database

                                  3)All discrepancy arise during reconciliation 

                                     Should be reviewed &resolved                                                          

 Reconciliation issues:

  • Ex: unschedule visit

               MRI assessments

               Accession ID

         Query management:

       Query management. In terms of clinical trials, a query is a request for clarification from trial sponsors to researchers. Such requests are made during data review, before database lock, and aimed at resolving errors and inconsistencies. The query management feature facilitates communication among data managers,sponsors, and other stakeholders. It helps faster resolve all questions.

  • Open queries : when site coordinator open query( seen the query)

  • Closed queries: when site coordinator opened ,answered query and closed query

  • Answered queries: when site coordinator opened and answered query

  • Canceled queries:when DM/biostatician/medical monitor/clinical coder enter  query in EDC and it can be canceled by these people

  • Queries  prepare  in excel sheet which discrepancy is present in data(EDC)

  • Query posting

        DM of CRO will provide weekly metrics

         Sponsor DM will review meetrics

         Metrics: can be open query by–DM,CRA,medical reviewer

         Queries like eg:subject part,unconfirmed missed date etc..,

  • Automated query—query populate in EDC when discrepancy is entered by site coordinate–edit checks

        Manual data listing

  •  SAS programme:

  • \


  • CRO will provide data listing-sponsor will review programme listing

  •  If not possible sponsor will prepare programme listing from EDC

  • EDC listing:

  • EDC–installed modules–reporter–Data listing  STUDY -

prod–submit==production clinical review —-from:ad,cm,medical—run–DATA–download file

  • Patient identifier

  • J-review

  • Spot fire

  • illuminate

        Manual data review

  • Manual checks

  •  Ex : Compare adverse events with cocomident medication 

Apply concatenate and vlookup

  1. Create Unique ID : SUB ID 

  2. Concatenate: 

Formula: Unique ID + the variable we want to compare (Record number)

  1. Create 2 concatenate records in both the listings

  2. Vlook up: 

Formula:vlookup(first concatenate cell no 1,second concatenate cell no 2 in different listing:$ columns name of the variable we want to compare $ total no of rows/records,1,0).

  1. Review coding dictionary MEDRA and WHO drug.

     

STUDY CLOSEOUT:

On the study completion, the database is locked so that no changes can be done to the information. After that, clean data is submitted to stakeholders for statistical analysis, reporting and, finally, publication of the results. However, all these steps are beyond the clinical data management workflow.

  •  LPLV

  • Database lock checklist:

  1. Ensure data is complete (both ecrf&non-ecrf)

  2. Perform final data listing review

  • Data entry

  • Data completion

  • Last Data transfer

  • Data review

  • Last reconciliation

  • Closing all discrepancies/issue trackers

  • Open queries-all close out

  • PI Signatures

  • SDV status-100% SDV

  1. SDV is completed for all CRDs by the CRA 

               After last patient last visit —-->data entry in ECRF —-->data completion—->Last data transfer—->closing all discrepancies/issue trackers in EDC—>Close out all open queries—->SDV(Source data verification) done by the CRA in site—100%SDV

  • Database lock checklist:

  •  Electronic archival:

  1. Preparing archival(a collection of historical documents or records providing information)

  2. It is done for secure retention maintaince & retrieval of data which goes to the trial master file


TERMS

 Go-live: 

After study start up--Database ready in EDC--site --subject enroll---Site PI(Doctor) enters patient details time from FPFV and LPLV. 

Split deployment:

In start up step skipping edit check document step and done with remaining ecrf specification,UAT

Blinding: 

Not aware of anything about  drug

Open/Unblinding:

Aware of every thing about drug

Double blinding:

Nor subject/Doctor/the company aware of drug

SDV:

source data verification=CRA-->site-->verify site data with EDC

Randomization:IRT-->IRT ENTER DATA IN

Randomly assigning something to subjects

Example:oncology 

study-->age:18-50-->100 subjects-->information-->computer-->computer gives each participant a code-->code number are randomly assigned

1 2 3 4 5 subjects

computer assigned

3 5 1 2 4 subjects-->Treatment starts


Place-bo:

It looks like a drug but there is no therapeutic active due to minimize patient bias

Screening:

example:Pass --10 subjects) enrollment different-->not possible of above criteria-->changes

               fail--40 subjects) 

screening based on mainly only inclusion and exclusion certeria.

FPFV:

When approval got from IRB, the site started clinical trials. Beginning of the clinical trial, the patient comes first to FPFV(first patient first visit) and starts data entry in the database(EDC).

LPLV:

End of clinical trial which patient comes last  for study

Disposition date:

When adverse event starts—> Treatment start—-->end of the treatment (date){last day

outsource

Outsourcing means that you hire outside resources to help you complete tasks or projects. These might include freelancers or agencies that specialize in performing a particular type of task or project. For example, hiring a digital marketing agency is a way to outsource your social media management.

Inhouse

In-house resources, on the other hand, are your existing employees — including yourself. When you handle a task or project in-house, you assign one or more of your team members to work on it.

Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply






                                        

                                           









    




    

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