Subject Screening & Enrollment
Screening Log
Documents and tracks all potential subjects screened for the protocol.
Subject Enrollment Log
Documents and tracks the progress of subjects enrolled in the study.
EQuIP Hint
Visit the EQuIP website for templates and guidance for developing
and using study logs, such as the Subject Enrollment Log template and
guidance and the Screening Log template and guidance.
www.childrenshospital.org/research/equip
EQuIP Hint
During the course of the protocol, if you want or need to capture
additional information (i.e. contact info, completed follow-up visit) on
a study document, such as a screening or enrollment log - REVISE
IT! Likewise, if you find you no longer need certain info – REVISE
IT! Make your study documents work for you.
Simply amend the study document accordingly and file the older
version(s) behind the new one. NEVER DISCARD OLD VERSIONS
and never re-enter past information in new study document, unless the
corresponding version is attached. Remember to document when and
why study log/document was changed in an attached memo-to-file, or
in a note clearly stated on the updated version.
Study Regulatory Binder [V.2]
Manual of Operations (MOO) or
Standard Operating Procedures (SOPs)
Current Manual of Operations (MOO) or
Standard Operating Procedures (SOPs)
The most updated version of the MOO/SOPs.
It is recommended to file this version in front for easy reference.
Out of Date MOO/SOPs versions
All outdated versions of the MOO/SOPs.
It is recommended to file outdated versions behind the current MOO/SOPs.
All outdated versions should be clearly labeled.
EQuIP Hint
Visit the Clinical Research Program (CRP) website for guidance in
developing a study-specific MOO.
http://crp-apps/intranet/crp/ResearchPracticeGuidelines/tabid/116/Default.aspx
EQuIP Hint
Place a binder clip on the right side of all expired MOO/SOPs versions
to prevent research staff from accidentally referencing them.
EQuIP Hint
For each MOO/SOP version, include the version date and number in
the footer for easy identification.
) REMINDER
The FDA views MOOs/SOPs as required documents. If your protocol
is regulated by the FDA, MOO/SOPs should be developed.
Definitions
Manual of Operations (MOO): a reference document that outlines the details of how to
operationalize the scientific protocol and conduct all study-specific procedures.
[CRP: “Guidelines for Developing a Manual of Operations”]
Standard Operating Procedures (SOPs): detailed, written instructions to achieve
uniformity of the performance of a specific function.
[ICH E6: Good Clinical Practices, 5.1]
Study Regulatory Binder [V.2]
Study Protocol
Approved Study Protocol
The most updated, currently approved protocol version must be on file.
It is recommended to file this version in front for easy reference.
Out of Date Study Protocol(s)
All out of date version(s) of the protocol must be on file.
It is recommended to file out of date versions behind the current version.
All out of date versions should be clearly labeled.
EQuIP Hint
Place a binder clip on the right side of out of date protocol versions to
prevent research staff from accidentally referencing them.
EQuIP Hint
For each protocol version, include the version date and number in the
footer for easy identification.
) REMINDER
The CCI requires that the study protocol (Part B of CCI application) is
updated to include all proposed amendments at the time of submission.
Once the CCI/IRB has approved requested amendments, file the
updated protocol in front of section for easy reference; label the
previous protocol version to clearly indicate it is out of date; and notify
all research staff immediately of the updated changes and of the new
protocol version on file.
Study Regulatory Binder [V.2]
Informed Consent and Assent Forms
Approved Informed Consent and Assent Forms
The most updated, currently approved consent/assent forms must be on file.
It is recommended to file the current version in front for easy reference.
Expired/Out of Date Informed Consent and Assent Forms
All expired/out of date version(s) of the consent/assent forms must be on file.
It is recommended to file expired versions behind the current approved
version. All expired versions should be clearly labeled.
Consent Revision Log (optional)
Tracks the changes/amendments between consent/assent form versions, the
date amendments were submitted for CCI review and the final approval date.
EQuIP Hint
) REMINDER
Place a paper clip on the right side of all expired consent/assent
versions to prevent research staff from accidentally referencing them.
Always use the Informed Consent Library to ensure you are using
the most recently approved consent version.
File one copy of the currently approved informed consent form in the
study regulatory binder, but use the Informed Consent Library to
obtain a copy of the consent form for each new potential subject, and
for submission for subsequent CCI applications and reviews.
http://chbcfapps/research/consents
Study Regulatory Binder [V.2]
Memo-to-Files
Memo-to-Files
A note or memo that documents and explains any study discrepancies and
deviations, or clarifies any questionable data or study procedures.
A memo-to-file generally includes the following information:
1. Topic of memo/event (e.g. informed consent, subject visit, IRB/CCI
communication)
2. Date of event
3. Detailed Description of event and any follow-up as necessary
4. Reason event occurred
5. If applicable and possible, actions taken to prevent future action
Document Log
The Document Log provides a system to track where study documents, that are
not stored in the regulatory binder, are located.
See EQuIP Website for sample of document log www.childrenshospital.org/research/equip
) REMINDER
Consider if it is relevant to store a copy of the memo-to-file in another
location (i.e. w/consent form, in subject folder, etc.) to ensure all
pertinent documentation is easily accessible.
Study Regulatory Binder [V.2]
Adverse Events & Unanticipated Problems
Documentation of Adverse Events/Unanticipated Problems
For each reportable adverse event and unanticipated problem, a copy of the
following must be maintained in study files:
1. Complete copy of CCI/IRB form Unanticipated Problem Involving Risks to Subjects
or Others Including Adverse Events as submitted, including all attached supporting
documentation (e.g. event summary, consent forms).
If event does not have to be submitted to CCI/IRB for review, PI must still keep
complete and adequate documentation of event.
2. Pertinent correspondence regarding event
3. Final CCI/IRB Acknowledgement Letter
It is recommended to file documents by specific adverse event and
unanticipated problem, then in reverse chronological order by
acknowledgement date.
Adverse Event and Unanticipated Problem Log (optional)
Tracks adverse events and unanticipated problems occurrence and submission
to and acknowledgement by CCI/IRB (if applicable).
EQuIP Hint
Visit the EQuIP website for templates and guidance for developing
and using study logs, such as the Adverse Event/Unanticipated
Problem Log. www.childrenshospital.org/research/equip
) REMINDER
A copy of the AE report should be placed in the subject file as well.
) REMINDER
Review the DSMP and submit to the DSMP/Monitor as appropriate.
Additionally, if study has Sponsor and/or outside monitor or
coordinating center, contact them to ensure all events are reported in
compliance with the sponsor’s/coordinating center’s policy.
) REMINDER
Read CCI Policy and Guideline: Unanticipated Problems Involving
Risks to Research Subjects and Others Including Adverse Events to
determine which events must be reported to the CCI/IRB and how.
Regardless if it is reported to the CCI/IRB, the event still must be
documented in the PI study files.
Study Regulatory Binder [V.2]
Protocol Deviations and Exceptions
Documentation of SIGNIFICANT Protocol Deviations/Exceptions
For each Significant Protocol Deviation/Exception, a copy of the following
must be maintained in study files:
1. Complete copy of CCI/IRB Significant Deviation/Exception Report Form as
submitted, including all attached supporting documentation
2. Pertinent correspondence regarding event
3. Final CCI/IRB Acknowledgement Letter
It is recommended to file documents by specific deviation/exception event,
then in reverse chronological order by acknowledgement date.
Documentation of MINOR Protocol Deviations/Exceptions
All Minor Protocol Deviations and Exceptions must be documented according
to CH/CCI Policy in a memo-to-file or Deviation Log, and submitted at the
time of next CCI/IRB continuing review. A copy of all minor deviations and
exceptions must be maintained in study files, no matter how they are
documented.
EQuIP Hint
Visit the EQuIP website for templates and guidance for developing
and using study logs, such as the Minor Deviation Log.
www.childrenshospital.org/research/equip
EQuIP Hint
File the Deviation Log in the front of this section is the document is
used/referenced frequently.
) REMINDER
Read CCI Policy and Guideline: Modifications: Exceptions and
Deviations to determine which events are significant vs. minor and
how they should be reported to the CCI/IRB.
) REMINDER
If study has Sponsor or coordinating center, contact them to ensure all
events are reported in compliance with the sponsor’s/coordinating
center’s policy.
Study Regulatory Binder [V.2]
Data and Safety Monitoring
All Data Safety Monitoring Reports
Copies of all reports and summaries from the Data Safety Monitoring Board.
Each report should be filed with the CCI/IRB acknowledgement of receipt and
review (letter or email).
Documentation of compliance with Data Safety Monitoring Plan
Documentation that the data and safety monitoring plan was carried out in
compliance with what the CCI/IRB approved. For example:
ƒ
ƒ
Emails documenting reporting of AEs as outlined in protocol
Memo-to-files documenting routine review of protocol data as documented in the
protocol’s DSMP
List of Data Safety Monitoring Board Members and affiliations
EQuIP Hint
Visit the CCI website for information on when DSMP/Bs are required.
www.childrenshospital.org/research/irb
EQuIP Hint
Visit the CRP’s website for guidelines on developing a Data and
Safety Monitoring Plan (DSMP) and for formation of Data and Safety
Monitoring Boards (DSMB).
http://crp-apps/Intranet/Default.aspx?alias=crp-apps/intranet/crp
) REMINDER
Per CCI policy, copies of all Data Safety Monitoring reports and other
similar reports should be submitted to the CCI for their files.
Definitions
Data Safety Monitoring Plan (DSMP): a plan to monitor subject safety in trials which
carry risk or are performed in vulnerable populations
Data Safety Monitoring Board (DSMB): an independent board which carries out the
data and safety monitoring plan
Study Regulatory Binder [V.2]
Recruitment Materials
Recruitment Materials
Copies of all CCI/IRB-approved recruitment materials used throughout the
study’s history must be on file.
Recruitment materials that are no longer used or are outdated (revised version
now in use) must be retained for reference. All outdated versions should be
clearly labeled (e.g. “EXPIRED”, “No Longer in Use”).
It is recommended to file the currently approved and most used recruitment
materials in front for easy reference.
Recruitment Log (optional)
Tracks all recruitment activity, and may be used to measure success of
recruitment activities based on enrollment.
EQuIP Hint
Visit the EQuIP website for templates and guidance for developing
and using study logs, such as the Recruitment Log.
www.childrenshospital.org/research/equip
Definitions
“Complete” means the entire submission (the application, including all consent and
assent forms, surveys/questionnaires, recruitment materials, appendices and all other
study documents).
Study Regulatory Binder [V.2]
Case Report Forms (CRFs) &
Study & Subject Documents
Current Case Report Forms (CRFs), Surveys & Questionnaires
A current and complete set of blank case report forms (CRFs), surveys and
questionnaires.
Out of Date Case Report Forms (CRFs), Surveys &
Questionnaires
All out of date version(s) of the case report forms, surveys and questionnaires
should be on file.
It is recommended to file out of date versions behind the current version.
All out of date versions should be clearly labeled.
Source Document List
A list of the source documents (original records that capture study data) that
will be used to verify study data captured on the CRFs.
Study and Subject Documents
A blank copy of all other study and subject documents used to capture and
document events and data, including (but not limited to):
ƒ Surveys and questionnaires (to be completed by subjects)
ƒ Subject Inclusion/Exclusion Checklist
Checklist used to verify and document that each subject has met all eligibility requirements
ƒ Study Visit Checklist
Checklist used to verify and document that each subject completed all required procedures for
each study visit, and if not, the reason why.
) REMINDER
The Clinical Research Program (CRP) can provide templates for
and/or assist in the development of case report forms and survey
instruments, to allow for efficient and consistent data collection.
For more information on CRP services, visit their website:
http://crp-apps/intranet/crp/CoreServices/ServiceDescriptions/tabid/176/Default.aspx
Definitions
Case Report Form (CRF): a printed or electronic document designed to record all of the
protocol required information and data for each study subject. CRFs are used to
standardize the collection of study data.
Source Documents: original records or certified copies that first capture required
study information/data and activity that is necessary for the reconstruction and
evaluation of the study trial.
Study Regulatory Binder [V.2]
Study Staff Logs and CVs
Roles & Responsibilities Log
Outlines which research staff member is responsible for each study procedure
and responsibility as approved in the study protocol.
Staff Signature Log
Document the signatures and initials of all research staff authorized to make
entries and/or corrections on Case Report Forms or other study documents
used for data analysis.
Research Staff CVs and Qualifications
If the protocol has an IND/IDE, copies of the CVs and staff qualifications
should be on file and up to date for the Investigator and all research staff. It is
recommended that the CVs have been updated within the past 2 years.
Training Documentation Log
Document that adequate training of the research staff has been conducted.
EQuIP Hint
It is recommended that CVs be updated and, signed and dated every 2
years to verify that information is accurate and current.
EQuIP Hint
Visit the EQuIP website for templates and guidance for developing
and using study logs, such as the Study Staff Log and guidance and the
Roles and Responsibilities template and guidance.
www.childrenshospital.org/research/equip
Study Regulatory Binder [V.2]
CCI/IRB Documentation
Complete Applications and Documentation for Reviews of New
Protocol, Continuing Reviews, Amendments and 3YR Rewrites.
For each review, a copy of the following must be maintained in study files:
1. Complete Application as submitted to CCI/IRB, including consent forms, surveys,
appendices and other attachments submitted for review.
2. Original CCI/IRB Action Letters and PI Responses
3. Pertinent correspondence regarding review
4. Final Approval Letters
It is recommended to file documents by specific review submissions, then in
reverse chronological order by approval date.
Pertinent Correspondence
All pertinent study-specific correspondence must be maintained.
It is recommended file correspondence in reverse chronological order.
CCI Tracking Log (optional)
Tracks submissions, CCI/IRB actions, PI Responses and correspondence.
It is recommended to use the CCI Tracking Log as it can provide a concise
reference of the protocol’s review history, as well as serve as a good index or
checklist of all documents that should be available in study files.
EQuIP Hint
Visit the EQuIP website for templates and guidance for developing
and using study logs, such as the CCI Tracking Log.
www.childrenshospital.org/research/equip
Definitions
“Complete” means the entire submission (the application, including all consent
and assent forms, surveys/questionnaires, recruitment materials, appendices and
all other study documents).
Study Regulatory Binder [V.2]
Scientific Review
Documentation of Scientific Review
Documentation for scientific review must include the following:
1. Copies of Scientific Reviewer Worksheets – specific to department/division
conducting review
2. Copies of pertinent correspondence (e.g. reviewer concerns, PI responses)
3. Documentation of department/division approval of scientific review
) REMINDER
Each Department/Division has its’ own scientific review requirements
and worksheets. Check the specific requirements for your
Department/Division as well as read the CH/CCI policy for Scientific
Review on CCI/IRB website (link below) prior to protocol submission.
www.childrenshospital.org/cfapps/research/data_admin/Site2206/mainpageS2206P19sublevel2.html
) REMINDER
Departmental scientific review must occur prior to submitting the
protocol for CCI/IRB review. The CCI/IRB application must include
documentation of department/division approval of scientific review,
copies of scientific reviewer forms and pertinent correspondence,
including all reviewers’ issues raised and the PI’s responses. Please
see the scientific review policy on the CCI website for more details.
Study Regulatory Binder [V.2]
FDA Form 1572: Statement of Investigator Form
FDA Form 1571: Investigational New Drug Application
IDE: Statement of Investigator Commitment
FDA Form 1572: The Statement of Investigator Form
For IND studies, the Principal Investigator must maintain a copy of the Form
1572 for themselves and all sub-investigators listed on the protocol as submitted
to the sponsor (IND holder).
These documents must be updated with the study sponsor each time there is a
change to the information originally provided. The PI must maintain copies
of all versions.
FDA Form 1571: Investigational New Drug Application
For IND studies, if the Principal Investigator is also the sponsor (IND holder),
the PI must maintain a copy of FDA Form 1571 in addition to Form 1572, as
submitted to FDA.
Copies of all versions of the Form 1571 submitted with amendments to the
FDA must be filed.
IDE: Statement of Investigator’s Commitment
For IDE studies, PI should maintain a statement of the investigator’s
commitment as outlined in 21 CFR 812.43 (c)
Study Regulatory Binder [V.2]
Regulatory Documentation:
Sponsor-Investigator IND/IDE Holder
FDA Annual Reports
Copies of annual reports sent to the FDA. Copies must also be sent to CCI/IRB for their
records.
FDA Financial Disclosure Form and Information
A copy of the FDA Financial Disclosure Form from all investigators and any other related
information.
Correspondence with participating Investigators, IRBs, other Sponsors,
Monitors, and the FDA.
Copies of IRB approvals from all other sites.
CCI/IRB Composition
A copy of the current composition of IRB members and FWA number should be on file for
all sites.
Drug and Device Shipment and Disposal Records
Documentation of drug/device shipments to all sites and records of disposal of unused
product.
All Monitoring Reports
Copies of the monitoring reports for all investigators should be on file with
acknowledgement from their IRBs.
AE/Unanticipated Events Reports from Other Sites.
Complete documentation of AEs/Unanticipated Events from other sites. Documentation
that pertinent information was disseminated to all sites.
Other Required Documents
See IND/IDE Sponsor-Investigator Responsibilities Checklists for a list of other required
documents. www.childrenshospital.org/research/equip
) REMINDER
The current version of CCI/IRB Roster is on the CCI website:
www.childrenshospital.org/cfapps/research/data_admin/Site2206/mainpageS2206P7sublevel9.html
Older versions can be obtained by contacting your CCI administrator.
) REMINDER
Definitions
It is recommended that Financial Disclosure Forms are updated every
year, or at minimum when changes occur.
FDA Annual Reports: brief report on the study progress submitted to
the FDA by study sponsors. IND holders must submit a progress
report to the FDA within 60 days of the anniversary date that IND
went into effect (21 CFR 312.33). For IDE holders of a significant
risk device, a progress report must be submitted to the FDA at regular
intervals, but at least yearly (21 CFR 812.150).
Study Regulatory Binder [V.2]
Regulatory Documentation:
Investigator
FDA Financial Disclosure Form and Information
A copy of the FDA Financial Disclosure Form and any other related information as
submitted to the study sponsor should be maintained in study files.
Sample Label for Investigational Product
A copy of the labels placed on any investigational drug/device/product used in the study
must be maintained in study files to demonstrate compliance with applicable labeling
regulations, and to demonstrate appropriate instructions are provided to subjects.
CCI/IRB Composition
A copy of the current composition of IRB members must be on file to demonstrate that the
IRB is constituted in agreement with Federal Regulations and Good Clinical Practices.
Correspondence with Sponsor
Other Required Documents
) REMINDER
The current version of CCI/IRB Roster is on the CCI website:
www.childrenshospital.org/cfapps/research/data_admin/Site2206/mainpageS2206P7sublevel9.html
Older versions can be obtained by contacting your CCI administrator.
Study Regulatory Binder [V.2]
Monitoring Log/Report
All Monitoring Reports (required for all FDA studies)
Copies of all final follow-up reports from outside monitor
Each report should be filed with the CCI/IRB acknowledgement of receipt and
review (letter or email).
Monitoring Log (required for all FDA studies)
Documents all monitoring visits and reviews (e.g. site visits, FDA audits).
It is recommended to include date reports were submitted to the CCI.
EQuIP Hint
Visit the EQuIP website for templates and guidance for developing
and using study logs, such as the Monitoring Log
www.childrenshospital.org/research/equip
) REMINDER
Per CCI policy, copies of all outside monitoring reports and other
similar reports should be submitted to the CCI for their files.
Definitions
Monitor: oversee an investigation. Sponsors or contract research organizations (CROs)
monitors and oversees the progress of an investigation.
Monitoring Report: the monitor or sponsor records the findings, conclusions, and
action taken to correct deficiencies for each on-site visit to an investigator.
Study Regulatory Binder [V.2]
Drug/Device Accountability Log
Drug/Device Accountability Logs
A record to document the shipment, receipt, use of and disposal of all investigational
drugs/devices used for a study must be maintained. Contact the Research Pharmacy.
EQuIP Hint
Visit the EQuIP website for templates and guidance for developing
and using study logs, such as the Drug/Device Accountability Log
www.childrenshospital.org/research/equip
Study Regulatory Binder [V.2]
Laboratory Documentation
Normal Value/Range(s) for all medical, laboratory, technical
procedures and/or tests included in the protocol.
The Study Regulatory Binder must document what are the normal values and
ranges for all procedures and tests performed as part of the protocol. All
values and ranges should be updated as necessary over the course of the
protocol.
Certification/Accreditation for all medical, laboratory, technical
procedures and/or tests included in the protocol.
Certification/accreditation, documentation of established quality control
and/or external quality assessment, or other validation must be documented to
demonstrate the competency of the facility to perform required tests and to
support reliability of results.
Lab Director’s Curriculum Vitae (CV)
CV should be current within 2 years.
CLIA Certification
Certification of Analysis
Document which lists the tests, methods, specifications, and results of the inprocess, bulk, and final lot release tests for each bulk and/or lot of drug,
chemical, or vaccine manufactured.
Study Regulatory Binder [V.2]
Investigator’s Brochure (IB)
Report of Prior Investigations (ROPI)
Device Manual/Package Insert
Current Investigator’s Brochure/Report of Prior Investigations
or Device Manual/Package Insert
The most up to date version must be on file.
It is recommended to file this version in front for easy reference.
Out of Date Investigator’s Brochure/Report of Prior
Investigations or Device Manual/Package Insert
All out of date version(s) must be on file.
It is recommended to file out-of-date versions behind the current version.
All out of date versions should be clearly labeled.
EQuIP Hint
Investigational Brochure Updates provide documentation that the
investigator has been informed of relevant information in a timely
manner as it becomes available.
Correspondence regarding receipt of or distribution of new
Investigator Brochures should also be maintained.
EQuIP Hint
) REMINDER
Definitions
Place a binder clip on the right side of all out of date investigational
brochures to prevent research staff from accidentally referencing them.
The CCI/IRB must have the most current copy of the Investigator’s
Brochure/Report of Prior Investigations or Device Manual/Package
Insert on file. For the initial protocol submission and review (New
Protocol Application), you must submit 3 copies with the application.
After initial approval, you must submit the Investigator’s
Brochure/Device Manual/Package Insert to the CCI/IRB only when it
has been updated.
Report of Prior Investigations: The report of prior investigations of
the device must include reports of all prior clinical, animal, and
laboratory testing of the investigational device. The report must be
suitably comprehensive and inclusive of adequate data and information
so as to justify that the proposed clinical investigation of the device
possesses an appropriate benefit-to-risk ratio.
Study Regulatory Binder [V.2]