Transcript Project Management SOP Presentation

CMRSC
Division of Hematology/Oncology
Training
Standard Operating Procedures for
Good Clinical Practice at the
Investigative Site
Section:
PROJECT MANAGEMENT
CMRSC 3.0 – Site-Sponsor/CRO
Communications
Purpose:
To describe the various ways of communicating
with the sponsor/CRO as all regulatory,
medical, and ethical requirements are fulfilled.
These include telephone and written
interactions.
These communications serve to protect the
safety and well-being of subjects by keeping
sponsors/CROs aware of study activities and
to ensure that studies are conducted
appropriately.
CMRSC 3.0 – Site-Sponsor/CRO
Communications
Communications overall:
1. Communicate regularly and appropriately
with the sponsor/CRO about all studyrelated activities
2. Document important conversations
Job aid! Telephone Contact Log
3. Keep originals or photocopies of all relevant
documentation, including facsimile
confirmations, e-mails. File these in the
study binder with appropriate documents.
CMRSC 3.0 – Site-Sponsor/CRO
Communications
Pre-study communications:
1. Send sponsor/CRO signed confidentiality
agreement (if needed).
2. Notify sponsor/CRO of decision to participate
in the study by telephone, fax, letter, e-mail,
etc.
3. Send sponsor/CRO signed protocol signature
page (if appropriate).
4. Submit all pre-study regulatory documents.
5. Send updated/revised documents as
necessary
CMRSC 3.0 – Site-Sponsor/CRO
Communications
Communications while the study is on-going:
1. Send the following by whatever means
the sponsor/CRO has requested (fax,
remote data entry, hardcopy, e-mail):
• Screening/enrollment forms
• Case Report Forms
2. Respond promptly to data queries as
requested
CMRSC 3.0 – Site-Sponsor/CRO
Communications
Communications while the study is on-going (cont.):
Copy sponsor/CRO on IRB communications
such as :
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Serious Adverse Event (SAE) reports
Investigational New Drug (IND) safety reports
amendment approvals
revised informed consent form
continuing IRB approval for the study
CMRSC 3.0 – Site-Sponsor/CRO
Communications
Communications when the study is complete:
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Inform the sponsor/CRO promptly if notified by
FDA of impending inspection.
Provide the sponsor/CRO with copies of all FDA
documentation (Form FDA 483, letters, etc)
generated as a result of the inspection
CMRSC 3.1 – Interactions with the IRB
Background:
The Institutional Review Board (IRB) is a group
appointed by CCHMC to protect the rights and
welfare of research subjects. Federal regulations
require that the IRB ensure that certain criteria for
approval of research are met prior to approving a
study.
By signing the Form FDA 1572, the PI ensures that the
IRB reviewing the research complies with the
regulations. The PI agrees to inform the IRB of any
changes to the protocol and any materials used to
recruit subjects, as well as any additional risks to
subjects associated with the investigational article.
CMRSC 3.1 – Interactions with the IRB
Purpose:
To describe how the Hem/Onc Division
communicates with the IRB throughout the
research process in order to ensure
compliance with the regulations and to protect
the safety and well-being of study subjects.
This SOP applies to those members of the
CMRSC involved in communicating with the
IRB to ensure appropriate management of all
clinical trial activity.
CMRSC 3.1 – Interactions with the IRB
Documenting IRB Compliance:
As requested by the sponsor/CRO, request a
copy of the IRB membership list and the
general assurance number.
CMRSC 3.1 – Interactions with the IRB
Communicating with the IRB at study start-up:
• Complete the initial IRB submission of the protocol. IRBapproved forms and checklists can be found at
http://www.cincinnatichildrens.org/research/administratio
n/irb/guidelines/researchprep.htm
• Obtain documentation of full IRB approval for the
protocol and informed consent form prior to study start.
Copy sponsor/CRO on correspondence.
• Maintain all documents in the appropriate study
regulatory binder.
CMRSC 3.1 – Interactions with the IRB
Communicating with the IRB while the study is on-going:
• Notify the IRB of any changes to the protocol and/or
informed consent, and of any new information from the
sponsor regarding the investigational drug or article.
• Submit periodic report form for renewal of the protocol at
a frequency specified by the IRB. The report form can
be found at:
http://www.cincinnatichildrens.org/research/administratio
n/irb/guidelines/default.htm
• Obtain documentation of IRB approval of amendments
and revisions to study-related documents, such as
advertisements or subject diaries, prior to
implementation, except to eliminate apparent hazard to
subject safety
CMRSC 3.1 – Interactions with the IRB
Communicating with the IRB while the study is ongoing (cont.):
• Notify the IRB promptly of all serious adverse
events occurring during the approval period for
the study. The SAE report form can be found at:
http://www.cincinnatichildrens.org/research/administratio
n/irb/guidelines/default.htm
• Promptly submit to the IRB all IND Safety reports
received from the sponsor.
• Report all routine AEs to the IRB as part of the periodic
or annual reporting requirements.
• Maintain all documents in the appropriate study
regulatory binder.
CMRSC 3.1 – Interactions with the IRB
Communicating with the IRB when the study is
over:
• Send a letter to the IRB stating that the study
has closed and the reason for closure (e.g., by
sponsor because study is complete, poor
recruitment, etc.) Include in the letter:
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Number of patients on study
Adverse events (if any)
Date study closed
When the monitor came for the close-out visit (if such
a visit was required).
CMRSC 3.2 – Regulatory Files and
Subject Records
Purpose:
To describe the steps for fulfilling all regulatory
and clinical requirements for collecting, filing
and storing study-related documents and
records.
The regulatory files and subject records, which
are periodically reviewed by the sponsor, and
upon request by the FDA, serve as the site’s
record of compliance with Good Clinical
Practice (GCP)
CMRSC 3.2 – Regulatory Files and
Subject Records
Definition:
Source Documents:
Original documents, data, and records (e.g., hospital
records, clinical and office charts, laboratory notes,
memoranda, subjects’ diaries or evaluation
checklists, pharmacy dispensing records, recorded
data from automated instruments, copies or
transcriptions certified after verification as being
accurate and complete, microfiches, photographic
negatives, microfilm or magnetic media, x-rays,
subject files, and records kept at the pharmacy, at
the laboratories, and at the medico-technical
departments involved in the clinical trial.
CMRSC 3.2 – Regulatory Files and
Subject Records
Collecting, filing, and storing study-related documents and
records:
• Regulatory Binder - For each study, create a
series of file folders or start a binder for
documents collected during the study.
Job aid! Regulatory Binder Checklist
• Maintain and update the regulator binders as
needed
• Retain copies of all original and revised
documents (protocol, investigator’s brochure,
informed consent form)
• Maintain a history of the conduct of the study.
CMRSC 3.2 – Regulatory Files and
Subject Records
Collecting, filing, and storing study-related
documents and records (cont.):
• Ensure that subject records and regulatory
binders are kept confidential and are
stored in a secure, limited-access location.
HIPAA! HIPAA! HORRAY!
• Prior to monitoring/auditor visits, review
content of regulatory binders and subject
records for completeness. Ensure files
are organized and complete after their
visit.
CMRSC 3.2 – Regulatory Files and
Subject Records
Collecting, filing, and storing study-related documents and
records (cont.):
• When the study is over, review the contents of
the regulatory binder and subject records by
comparing with the checklist (Regulatory Binder
Checklist)
• Archive regulatory binders/subject records
• Label storage boxes clearly
• Document inventory of storage boxes
• Store in a secure location for the required period
of time (as specified by sponsor).
CMRSC 3.3 – Sponsor/CRO
Monitoring Visits
Purpose:
To describe the steps followed by the CMRSC from the
time the monitor schedules a monitoring visit until all
follow-up activities associated with the visit have been
completed.
Monitoring visits are necessary to:
• Assess adherence to the protocol
• Review regulatory files for completeness
• Ensure appropriate study drug storage, dispensing, and
accountability
• Verify data in case report forms with source
documentation
• Meet with the Research Team and PI to discuss study
progress and any concerns raised as a result of the visit.
CMRSC 3.3 – Sponsor/CRO
Monitoring Visits
Scheduling the monitoring visit:
• Work with the study monitor to schedule a mutually
convenient date and time for the monitoring visit. Consider
the PI’s schedule as well.
Job aid! Regulatory Binder Checklist
Preparing for the monitoring visit:
• Schedule a suitable space for the monitor to work
• Ensure all regulatory documentation and case report forms
are complete and available
• Ensure all data queries are resolved to the extent possible
• Have needed patient HIM records available for the visit
• Inform the study pharmacist to prepare for drug storage and
accountability records review
CMRSC 3.3 – Sponsor/CRO
Monitoring Visits
Managing the monitoring visit:
• Ensure that the monitor signs the visit monitoring
log (should be in the regulatory binder)
• Ensure that the monitor has all the documents
he/she will need, update the monitor on any studyrelated issues.
• At the end of the visit, meet with the monitor to
review any issues pertaining to:
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Adherence to the protocol
Review of the regulatory binders
Verification of data in the CRFs with source documents
Study drug storage, dispensing, accountability
CMRSC 3.3 – Sponsor/CRO
Monitoring Visits
Managing the monitoring visit (cont.):
• Discuss any payment issues, if necessary
Following-up after the monitoring visit:
• Ensure that all issues identified for resolution
or follow-up at the monitoring visit are
addressed.
CMRSC 3.4 – Study Termination Visit
Purpose:
To describe the process followed when the sponsor’s
monitor conducts a study termination visit to:
• Review all regulatory files for completeness
• Complete the verification of all data in case report forms
with source documentation
• Meet with the research team to discuss review of the
above, drug accountability, possibility of a QA and/or
FDA audit, and requirements for data storage
Exception: Consortium group studies, upon closure or
termination, may not result in a study termination visit;
however, all steps in this SOP should be considered for
proper closure of even those studies at CCHMC
CMRSC 3.4 – Study Termination Visit
Scheduling the study termination visit:
• As soon as possible after the last patient has completed all
scheduled visits associated with the study, arrange a
mutually convenient data and time for the study monitor to
conduct the study termination visit.
Job aid! Study Termination Visit Checklist
Preparing for the study termination visit:
• Ensure all regulatory documents and case report forms not
previously monitored are complete and available for review
• Ensure all data queries have been resolved to extent
possible
• Ensure the patient’s medical records are available
• Inform the study pharmacist that study drug will be
inventoried and drug records will be reviewed
CMRSC 3.4 – Study Termination Visit
Managing the study termination visit:
• Ensure the monitor has all documents
required to complete the termination visit.
Update him/her on any study-related
issues.
• At the end of the visit, meet with the monitor
to discuss any issues related to:
– Regulatory files, source data verification, study
drug reconciliation, possibility of QA and/or FDA
audit, and requirements for data retention and
storage
CMRSC 3.4 – Study Termination Visit
Managing the study termination visit (cont.):
• If study data was submitted via remote data entry
(computer entry), determine when hard copies of
all CRFs will be provided to the site.
• Review the sponsor’s requirements for protecting
the integrity of the electronic data.
• Discuss the sponsor’s requirements for patient
follow-up for serious adverse events.
• Discuss the possibility of publication of the data,
and future studies.
• If necessary, discuss final payment(s).
CMRSC 3.4 – Study Termination Visit
Following-up after the study termination visit:
• Ensure that the study drug is either prepared for return
shipment to the sponsor or disposed of at the site per the
sponsor’s WRITTEN request.
• File copies of the study drug packing slips and shipment
receipts – or – provide the sponsor with documentation of
the previously authorized study drug disposal and file site
copy in regulatory binder
• Ensure return or destruction of all other study-related
materials.
• Ensure that any equipment on loan is returned.
• Inform the IRB that the study is over and submit the final
report….copy the sponsor.
• Resolve final data queries, check study files for
completeness, send files to secure storage if needed.
CMRSC 3.5 – Investigational Drug
Accountability, Storage, Dispensing,
and Return
Purpose:
To describe the processes for the order,
receipt, storage, dispensing, reconciliation,
and return or authorized destruction of the
investigational drug (study drug).
This SOP applies from the time the drug is
ordered until it is either returned to the
sponsor or destroyed on-site at the
sponsor’s request.
CMRSC 3.5 – Investigational Drug
Accountability, Storage, Dispensing,
and Return
Definitions:
Blinding/Masking: a procedure in which one or more parties
of the trial are kept unaware of the treatment
assignment(s). Single blinding usually refers to the
subject(s) being unaware, and double-blinded usually
refers to the subject(s), investigator(s), monitor, and, in
some cases, data analyst(s) being unaware of the
treatment assignment(s)
Investigational Product: a pharmaceutical form of an active
ingredient OR placebo being tested or used as a
reference in a clinical trial
Randomization: the process of assigning trial subjects to
treatment or control groups using an element of chance
to determine the assignments in order to reduce bias
CMRSC 3.5 – Investigational Drug
Accountability, Storage, Dispensing,
and Return
Ordering study drug:
• Only those authorized by the PI may order study drug. This
is indicated by the 1572 form or other authorized means of
delegation per the study.
Receipt/inventory of study drug:
• All investigational drugs should be shipped to the CCHMC Investigational
Drug Pharmacy
• Upon receipt of investigational drug, inventory the shipment, ensuring the
packing slips match exactly what was sent (check amount, lot numbers,
quantity per container)
• Resolve discrepancies promptly
• If required, acknowledge receipt as requested by sponsor/CRO
• Retain copies of everything for the regulatory files
• Ensure any supplies needed for the blinding of the study are available
CMRSC 3.5 – Investigational Drug
Accountability, Storage, Dispensing,
and Return
Storage of study drug:
• Study drug must be stored:
– In a secure location
– According to storage requirements (temperature,
humidity, light)
– Maintain logs of storage conditions, if required
• Follow any special requirements for controlled substances
• Ensure that the randomization code, if being used, has been
received
CMRSC 3.5 – Investigational Drug
Accountability, Storage, Dispensing,
and Return
Dispensing of study drug:
• Each time study drug is dispensed, complete the drug
accountability form (usually done by Investigational
Pharmacy)
• The study may require that used containers are returned to
the study pharmacist; document if containers are missing
• Document discrepancies between amounts used by the
subjects and amounts expected to be returned. Document
reasons.
• Ensure study drug is within an appropriate expiration date
• If appropriate, alert the monitor when additional supplies will
be required
• If emergency breaking of the study drug blind is medically
necessary, document all circumstances appropriately.
CMRSC 3.5 – Investigational Drug
Accountability, Storage, Dispensing,
and Return
Return/destruction of study drug:
• At the conclusion of the study, ensure all documentation
regarding receipt, storage, dispensing, and return of used
containers is complete, accurate, and ready for review at the
monitor’s termination visit.
• Destruction of the study drug at this site, upon written
authorization from the sponsor to do so, may be undertaken
so long as such procedures are permitted by the CCHMC
Biohazard Materials Policy and Safety policies
• Provide the sponsor with written documentation of the
destruction of the study drug. Maintain a copy in the
regulatory files.
Of course there’s another quiz!
• CMRSC SOPs – Project Management Section
Quiz