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Essential Documents for Clinical Essential Documents for Clinical Trial ResearchTrial Research

Erin Erin CherbanCherban, , MScMSc., CCRP., CCRP Centre for Health Evaluation and Outcome SciencesCentre for Health Evaluation and Outcome Sciences Manager, Clinical Research Development Office Manager, Clinical Research Development Office

Document ExamplesDocument Examples

See the following examples at the end of See the following examples at the end of this presentation:this presentation:•• GCP Guidance, Section 8GCP Guidance, Section 8•• Trial Master File DocumentsTrial Master File Documents•• NoteNote--toto--File templateFile template

DocumentationDocumentation

Documentation is critical in clinical Documentation is critical in clinical research. Protect yourself and your research. Protect yourself and your staff by following this rule:staff by following this rule:

““If itIf it’’s not written down, it did not s not written down, it did not happenhappen””

What are essential documents?What are essential documents?Essential Documents are those Essential Documents are those

documents that individually and documents that individually and collectively permit evaluation of the collectively permit evaluation of the

conduct of a trial and the quality of the conduct of a trial and the quality of the data produced. These documents serve data produced. These documents serve

to demonstrate the compliance of the to demonstrate the compliance of the investigator, sponsor, and monitor with investigator, sponsor, and monitor with

the standard of GCP and with all the standard of GCP and with all applicable regulatory requirements.applicable regulatory requirements.

Source: Source: The International Conference on Harmonization, Topic E6: The International Conference on Harmonization, Topic E6: Good Clinical Practice: Consolidated Guideline, Section 8. Good Clinical Practice: Consolidated Guideline, Section 8.

Where to seek guidance?Where to seek guidance?

The International Conference on The International Conference on Harmonization, Topic E6: Harmonization, Topic E6: Good Good Clinical Practice: Consolidated Clinical Practice: Consolidated GuidelineGuideline

Website:Website:http://www.hchttp://www.hc--sc.ca/dhpsc.ca/dhp--mps/prodpharma/applicmps/prodpharma/applic--demande/guidedemande/guide-- ld/ich/efficac/e6_e.htmlld/ich/efficac/e6_e.html

GCP Consolidated GuidelineGCP Consolidated Guideline

= = Minimum list of documentsMinimum list of documents

Essential documentsEssential documents

GCP Guidelines are suitably vague, your GCP Guidelines are suitably vague, your sitesite’’s trial master file must include the s trial master file must include the documents unique to your site:documents unique to your site:•• National: Health Canada National: Health Canada No Objection Letter.No Objection Letter.

•• Local: Fraser Health approval documents Local: Fraser Health approval documents including Letter of Authorization to Conduct including Letter of Authorization to Conduct Research.Research.

•• Sponsor: Data queries, monitorSponsor: Data queries, monitor’’s reports, and s reports, and adverse event reports.adverse event reports.

Documentation Documentation

Controlling paper workControlling paper work

vs.vs.

A satisfied site, sponsor and regulatory A satisfied site, sponsor and regulatory authoritiesauthorities

= Trial Master File= Trial Master File

Trial Master FileTrial Master FileAt the beginning of the trial determine the At the beginning of the trial determine the space and filing logistics for your site.space and filing logistics for your site.•• Space: Where can you retain the documents in Space: Where can you retain the documents in

a secure fashion? Where can you store a secure fashion? Where can you store documents that are not needed daydocuments that are not needed day--toto--day?day?

•• Filing: What is your preferred method, what is Filing: What is your preferred method, what is your sponsoryour sponsor’’s preferred method? Discuss at s preferred method? Discuss at outset of the trial.outset of the trial.

Establish a system at the beginning of theEstablish a system at the beginning of thetrial, your files will remain organized.trial, your files will remain organized.

Trial Master FileTrial Master FileFiling:Filing:• Keep files in chronological order.Keep files in chronological order.•• Neat and complete files.Neat and complete files.•• A A ““paper trailpaper trail”” explanation of all aspects explanation of all aspects of the trial.of the trial.•• Update files continuously.Update files continuously.•• Do not discard older documents, store Do not discard older documents, store them.them.

The paper trailThe paper trail……..Consider documenting:Consider documenting:

1)1) Evidence of supervision of trial Evidence of supervision of trial responsibilitiesresponsibilities

For example: For example:

•• agendas and minutes from research team agendas and minutes from research team meetings.meetings.

•• investigator decisions about trial related investigator decisions about trial related procedures and subjects (consider email or procedures and subjects (consider email or a more formal meeting with notes)a more formal meeting with notes)

The paper trailThe paper trail……..

2)2) Your siteYour site’’s standard operating procedures s standard operating procedures (SOPs)(SOPs)

•• A Health Canada auditor will look for A Health Canada auditor will look for documented proof of your sitedocumented proof of your site’’s s procedure for the informed consent procedure for the informed consent process.process.

•• They will also look for documented proof They will also look for documented proof that each subject is eligible for the trial.that each subject is eligible for the trial.


3) Subject visit tools/checklists and notes3) Subject visit tools/checklists and notes

•• Use or create subject visit tools to include Use or create subject visit tools to include in the subjectin the subject’’s study file (for example, lab s study file (for example, lab test and procedures required at the visit).test and procedures required at the visit).

•• Keep written, detailed Keep written, detailed ““progress notesprogress notes”” of of each study visit.each study visit.


3) 25 Year Document Retention Requirement3) 25 Year Document Retention Requirement

•• For trials authorized by Health Canada For trials authorized by Health Canada you need proof that the trial documents you need proof that the trial documents will be retained for 25 years.will be retained for 25 years.

•• Ask the sponsor for this documentation (at Ask the sponsor for this documentation (at the beginning of the study this will remind the beginning of the study this will remind you to discuss longyou to discuss long--term archiving term archiving responsibilities and costs).responsibilities and costs).


4) Protocol Deviations4) Protocol Deviations

•• Remember to report protocol deviations Remember to report protocol deviations to your ethics committee and sponsor.to your ethics committee and sponsor.


5) Use Note5) Use Note’’ss--toto--FileFile

•• A helpful tool to record everything from A helpful tool to record everything from discrepancies to the physical location of discrepancies to the physical location of files. files.

Remember: It is okay if you make a mistake, Remember: It is okay if you make a mistake, but document it and include corrective but document it and include corrective action. Do not hide it.action. Do not hide it.


5) Regularly print your emails and file them 5) Regularly print your emails and file them rather than trying to remember what was rather than trying to remember what was important at a later date.important at a later date.

6) Use any method/format that works for 6) Use any method/format that works for your site/investigator but remind everyone your site/investigator but remind everyone that without a paper trail, there is no audit that without a paper trail, there is no audit trail.trail.

Keep your Files CurrentKeep your Files CurrentDesignate a staff member to update files:Designate a staff member to update files:

•• Delegation of responsibility/signature log Delegation of responsibility/signature log signed and dated as neededsigned and dated as needed

•• Current CVs and medical licensesCurrent CVs and medical licenses

•• Continuing education for all personnelContinuing education for all personnel

•• Lab Lab normalsnormals and accreditationand accreditation

Keep your Files CurrentKeep your Files Current•• Calibration of study equipmentCalibration of study equipment

•• SAE log or regulatory submission logSAE log or regulatory submission log

•• Subject screening, enrolment and Subject screening, enrolment and identification logs.identification logs.

•• Move older versions of the investigatorMove older versions of the investigator’’s s brochure, protocol and informed consents brochure, protocol and informed consents into on site storage.into on site storage.

Simplify your files . . .Simplify your files . . .

Create a central file for documents used in Create a central file for documents used in many studies, for example:many studies, for example:•• CVs and medical licensesCVs and medical licenses•• Staff continuing educationStaff continuing education

In your trial master file,In your trial master file, reference the locationreference the locationof these documents using a noteof these documents using a note--toto--file.file.

Storage/ArchivingStorage/Archiving•• Consider onConsider on--site site ““archivingarchiving”” of documents of documents that are outthat are out--dated, but that must be retained.dated, but that must be retained.

For example, move older versions of the For example, move older versions of the protocol and informed consent, this will protocol and informed consent, this will prevent confusion and create space for dayprevent confusion and create space for day-- toto--day documents.day documents.

•• Document the location with a noteDocument the location with a note--toto--file in file in your trial master file.your trial master file.

Key Subject DocumentsKey Subject Documents

•• Source documentsSource documents

•• Completed case report formsCompleted case report forms

•• AEsAEs and and SAEsSAEs

Thank youThank you

Questions?Questions?

Email:Email:

[email protected][email protected]

Tel: 604Tel: 604--806806--88718871