essential good clinical practice documents -...

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Essential Essential DocumentsDocuments

DMID/ICSSCDMID/ICSSC

10/7/08

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What are Essential What are Essential Documents?Documents?

Documents that permit evaluation of the conduct of a trial and the quality of the data

Auditable

Successful management of a clinical study

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List of Essential DocumentsList of Essential Documents

Before

During

After

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Before the Clinical StudyBefore the Clinical Study

Majority of the essential documents required by ICH/GCP need to be on file before the study starts

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During the Clinical StudyDuring the Clinical Study

Updates

Communication and reports

Adverse event reporting

Participant-related

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After the Clinical StudyAfter the Clinical Study

Final reportsClose-out monitoring reportReport by investigator to IRB/IECClinical study report, if required

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Document RetentionDocument Retention

CCP

Where?

How long?

Who is responsible?What if the investigator retires?

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Direct Access to DataDirect Access to Data

Sponsor including sponsor’s monitors and auditors

IRB/IEC

Regulatory authorities

September 30, 2004

Version Control Guidelines

Refer to the Version Control Flow Chart following the guidelines. 1. Document dates

a. The person primarily responsible for the document will ensure the date the document is created or revised is identified on the first page and, when possible, incorporated into the header or footer of the document and appears on every succeeding page. It will be possible for more than one version of the draft document to have the same date but unlikely for more than one version of a final document to have the same date.

2. Version numbers a. The person primarily responsible for the document will ensure the current version

number is identified on the first page and, when possible, incorporated into the header or footer of the document and appears on every succeeding page.

3. Draft documents version numbers a. The first draft of a document will be “0.1”. b. Subsequent drafts will have an increase of “0.1” in the version number, e.g.,

“0.2”, “0.3”…….“0.9”, “0.10”. 4. Final documents version numbers

a. The Protocol Champion will deem a protocol or other document (consent/assent form, case report form, manual of procedures) final after all reviewers have provided final comments and the comments have been addressed.

b. The first final version of a document will be “1.0”. c. Subsequent final documents will have an increase of “1.0” in the version number.

5. Final documents undergoing revisions a. Final documents undergoing revisions will be “X.1” for the first version of the

revisions. Subsequent revision versions will increase by “0.1”, e.g., the third draft of version “2.0” would be “2.3”. When the revised document is deemed final, the version will increase by “1.0” over the version being revised.

b. A list of changes from the previous document will be kept. The list will be cumulative and identify the changes from the immediately preceding version number. The list can be incorporated into the new document or kept in the project files.

Generally, the first final protocol version submitted to FDA is 1.0 if it is an IND study. If it is not an IND study, the first final protocol version to be implemented is 1.0

September 30, 2004

Version Control Flow Chart

Version Control

Document Date Date the document is created or revised is identified on the first page and, when possible, incorporated into the header or footer

of the document and appears on every succeeding page

First Draft

1st draft is version “0.1” – subsequent drafts will increase by “0.1”

First Final

First final version will be version “1.0”

Revisions to a Final Version

Final documents undergoing revisions will be “X.1” for the 1st draft subsequent drafts will increase by “0.1”

All changes will be documented

Subsequent Finals

Version number will increase by “1.0” above the version being revised

Version Number Current version number is identified on the first page and, when possible, incorporated into the header or footer of the document

and appears on every succeeding page

Essential Documents Exercise Work in groups and find answers to the following questions. Use the DMID Regulatory Document Guidelines to assist you.

1. According to the DMID Regulatory File Document Guidelines, the Study Personnel Signature/Responsibility List must include the signature and initials of study staff that are currently authorized to make entries and corrections to the CRFs, as well as laboratory personnel, study staff that obtain informed consent, and study staff that are responsible for maintaining IRB/IEC documents.

True / False (circle one)

2. Blank copies of all final versions of case report forms must be included in the Regulatory Binder.


3. What is the purpose of the Regulatory Review History Log?

4. Every submission to the IRB/IEC must be maintained so that the submission

letter, copies of documents submitted, comments and questions received from the IRB/IEC, and the final IRB/IEC approval letter are kept together.


5. Only the original IRB/IEC version of the protocol needs to be included in the Regulatory Binder; any subsequent IRB/IEC amendments do not need to be maintained in the Regulatory Binder.


6. A final version of a protocol can have a version number 2.2 True / False (circle one) 8. Draft versions of protocols must be maintained in the Regulatory Binder True / False (circle one)

9. Copies of the blank original IRB/IEC approved consent form and subsequent IRB/IEC amendments to the consent forms need to be maintained in the Regulatory Binder


10. How should annual renewals (also called continuing review approvals) be maintained in the Regulatory Binder?

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Source DocumentationSource Documentation

DMID/ICSSCDMID/ICSSC

4/16/09

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What is a Source Document?What is a Source Document?

Original

DocumentDataRecord

David Borasky/FHI

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Examples of Source DocumentsExamples of Source Documents

Hospital records

Clinic and office charts

Subject diaries

Pharmacy dispensing records

Recorded data from automated instruments

Subject files

X-rays

Case Report Forms *

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Why Have Source Documents?Why Have Source Documents?

Confirm participant existence

Verify study data

Starting point for an audit trail

Tita Oronoz/FHI

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CRFs as Source Documents CRFs as Source Documents

Clinical observations are recorded directly on CRFIdentified in protocolNot meant to replace ALL source documentationMaintain list of CRFs to be used at siteOriginal CRF must be signed and datedExamples:

PE CRF

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The Golden Rule of The Golden Rule of Clinical ResearchClinical Research

Data recorded on Case Report Forms (CRFs) must be consistent with Source DocumentsAny discrepancies should be explained

Source Documents = CRFs

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Corrections to Source Corrections to Source DocumentsDocuments

The original value must remain visibleThe new value addedDate change was madeInitials of person making the changeExplain, if necessary Unacceptable correction methods:

Correction fluidObliterationErasure

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Certified CopiesCertified Copies

Certified copy = originalCertified as being an exact copy by authorized person e.g. medical records specialistCertified copy must be dated and signed