Transcript Clinical Drug Request

MARCH 2012
REGULATORY
MANAGEMENT
Marie D’Amico, CCRP
Manager, RTOG Regulatory Affairs
www.rtog.org
1
Disclaimer
The following presentation is being given for RTOG studies
only. The information represented here while current may
change due to changes within RTOG internal processes or
because of federal regulatory guidelines. Therefore, you may
not reproduce or distribute any of the presentation without
obtaining RTOG’s prior written consent.
www.rtog.org
2
MARCH 2012
Regulatory Documents
& the CTSU
www.rtog.org
4
Regulatory Documents
All regulatory documents for US, Canadian &
Non North American sites are submitted to the
CTSU for cataloguing and data entry
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Continuing Reviews
Approvals of amendments
IRB initial study approvals
IRB approved consent forms
• (translation required for Non English speaking
countries/provinces)
www.rtog.org
5
Continuing IRB Approval
•
•
IRB approval must continue until
Finite Studies
–
•
Non Finite Studies
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All subjects accrued have completed treatment and follow up
All subjects are deceased
Additional requirements for both finite & non finite studies
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No further accrual is anticipated
All data forms have been submitted
All queries to date have been resolved
RTOG approves the site for early closure (see form)
•
IRB approval remains necessary, even after RTOG study closure and until
RTOG termination unless all the above criteria/requirements have been met
•
Only RTOG can classify a study as "terminated" (Database locked)
•
Notification of Study Termination will be received via broadcast
•
A formal request is required for early closure when all criteria met
www.rtog.org
6
Form to Request Early IRB Closure
http://www.rtog.org/ResearchAssociates/RegulatoryInformation/EarlyIRBClosure.aspx
www.rtog.org
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Requests for Early IRB Closure
•
Request form must be submitted to and approved by RTOG
•
The Form has Multiple purposes
– Request consideration for early closure with IRB
– Request closure with IRB when no patients enrolled on study
– Transfer IRB responsibilities
•
RTOG response with approval of the request is required prior to taking
any closure action
•
Internal multi department review at RTOG HQ can take 7-10 business
days to complete
•
Sites will still be required to respond to queries even after study
closure with the IRB
www.rtog.org
8
Continuing IRB Approval
• IMPORTANT NOTE Full member institutions that have
affiliates that use the Full Member IRB as their IRB of record
must ensure that those affiliate/ Joint Center institutions had
also never put any patients on studies they are considering
closing with the IRB. If they have, then the main IRB must keep
this study open for annual review.
www.rtog.org
9
Special Handling
•
Handling of all other study specific regulatory documentation is
detailed in Sections 5.0 or 7.0 of the protocol
•
•
•
•
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Study Agent Shipment Form (SASF)
Sponsor required documentation
Questionnaires
Training Certifications
RT Certifications
•
Non English speaking Canadian & Non North American sites are
required to supply the Certified/Verified English translation and native
language copy of the IC with their regulatory approvals
•
Other special procedures may exist for Non North American sites
www.rtog.org
10
Correlative Components
•
Each participating institution must be prepared to participate in all correlative
components/have a plan in place to facilitate participation and must offer every patient the
opportunity to participate in these components.
•
ONLY THE PATIENT can decline to participate in the correlative components of a study
•
The majority of RTOG studies require varying degrees of specimen collection as part of
eligibility, stratification or protocol treatment.
•
Sites are encouraged to become more organized in their efforts and coordinate tissue
banking collections with other protocol required specimen collections whenever possible.
•
In the event tissue is collected/residing at another facility RTOG expects a good faith effort
to obtain the retrospective specimens but the site will not be penalized if it is not possible.
•
Prospectively the site must inform the collecting entity that future specimens collected are
expected to be forwarded along with the appropriate submission form for tissue banking
as noted in the protocol.
www.rtog.org
11
CTSU Forms & Guidance
Can be found on the RTOG website www.rtog.org
under RA/Regulatory Info/CTSU Filing Requirements
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IRB Certification Forms
310 Certification Form
IRB Transmittal Forms
Guidance for completing the forms
RSS Flow sheet
NCI Required Forms are also available here
– FDA 1572
– CTEP Supplemental Investigator Data Form (IDF)
– CTEP Financial Disclosure
www.rtog.org
12
Proper Labeling
Ensures Proper Processing
• Please identify all information submitted to the CTSU
with the institution’s NCI Code on the
transmittal/certification form
• If the submission covers more than one institution or
an entire CCOP all assigned individual NCI
institution codes covered under the approval must
be listed on the transmittal/certification form or
supplemental page
www.rtog.org
13
CTSU Forms
Transmittal/Certification
www.rtog.org
14
Resolving Regulatory Issues
• All issues for U.S., Canadian and Non North
American sites with submitted regulatory documents
should be handled directly through the CTSU.
RTOG does not have access to copies of regulatory
documents that have been submitted to the CTSU.
www.rtog.org
15
Checking Registration Status
Visit the CTSU Website: https://www.ctsu.org/public/
•
•
•
•
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Requires a CTSU username & password
Sites are identified by NCI Code
Lists all requirements for study
Lists items not in compliance
Now available for Non North American sites
www.rtog.org
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To obtain a CTSU password…
www.rtog.org
17
Points of Contact for the CTSU
•
•
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Help Desk: 1-888-823-5923
Regulatory Help Desk: 866-651-CTSU (2878)
E-mail for questions: [email protected]
For Regulatory Submissions:
• Fax Number: 215-569-0206
• E-mail : [email protected]
Mailing Address:
CTSU Regulatory Office
Coalition of National Cancer Cooperative Groups
1818 Market Street, Suite 1100
Philadelphia, PA 19103
•
Website: http://members.ctsu.org/
www.rtog.org
18
Record Retention
According to the NCI Investigator Handbook:
•
10.3 Retention of Records
FDA regulations require that all research records (including patient
charts, case report forms, x-rays and scans that document response, IRB approvals,
signed informed consent documents and all agent accountability records)
must be kept by the investigator for at least 2 years after an NDA or BLA has
been approved for that indication or the CTEP IND has been closed. CTEP
will notify investigators when these events occur. This requirement is an
explicit part of the FDA Form 1572,
http://ctep.cancer.gov/handbook/index.html
•
For NON IND Studies:
The point of reference used to determine the length of time required for record
retention for non IND studies would be RTOG’s termination date for the study,
which is when the database is locked and no further information would be required.
The recommended timeframe for record retention is 3 years past termination
The institution’s (and IRB’s) guidelines would also need to be considered.
www.rtog.org
19
Password Protected Documents
on the RTOG Website
• An RTOG user name and password may be required to gain
access to some password protected documents
• The username and password used for web registration will
permit access to these documents
• The application to obtain a username & password is now web
based. Paper submissions will no linger be accepted. Complete
the online application at the following link:
http://www.rtog.org/AboutUs/RTOGPasswordApplication.aspx
• The usual turnaround time for password authorization requests
is two business days
www.rtog.org
20
Informed Consent Concerns
•
RTOG provides an NCI and ACR IRB Approved consent template for each
protocol
•
RTOG prefers no changes be made other than to add local context
•
IRB requested additions to the document for clarity are permitted
•
The Deletion of any information should be avoided to preserve the integrity of
the document
•
The essential elements of the RTOG Informed Consent Template must remain
intact
•
IRB required deletions of risks and alternative procedures will require written
justification
•
Please refer to RTOG Guidance Document for making changes to the informed
consent template (revised 5/2010)
•
http://www.rtog.org/LinkClick.aspx?fileticket=d5UGGw5pEjc%3d&tabid=309
www.rtog.org
21
Informed Consent Approval
•
It remains your IRB’s responsibility to review and approve the
informed consent content and any changes made at the site level
•
A CERTFIED or VERIFIED English & native language translation of the
IC is required for Non English speaking Canadian & Non North
American sites
•
Please note the RTOG Regulatory Compliance Department does not
review consents. All consent content will be reviewed at time of audit.
•
Problems and deficiencies with IRB approved consents found during
the audit will be reported as appropriate.
www.rtog.org
22
Broadcasts & Summary of Changes
•
Information relating to protocol updates and amendments can be
found on the RTOG web site: www.rtog.org
•
RTOG suggest sites check the website regularly to assure they have
received all broadcast information
•
NCI requires that cooperative groups provide a Summary of Changes
which describes all of the changes made to a protocol, and indicates
whether the changes are administrative (update) or treatment related
(amendment)
•
On the website select Clinical Trials/Protocol Table, then the protocol
number:
–
Select “Summary of Changes” under Protocol Documents scroll through the
document to see all previous
– Select “Broadcasts”, from left column, a list of protocol specific broadcasts will
open.
www.rtog.org
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Finding Broadcasts & Amendments
On The Website
www.rtog.org
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Protocol Updates
•
Updates are editorial/administrative changes that RTOG is allowed to
make without prior NCI approval (updates are sent to NCI for their
information).
•
Examples of protocol updates might include:
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–
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correction of typos
changes/additions to administrative processes
change in the address for data submission
change in a Co-Chair’s contact information.
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Per NCI, an update cannot involve patient treatment or anything that
would impact patient safety.
•
The RTOG broadcasts indicate “IRB review of an update is not
required; however, these changes must be reported to the site IRB”
www.rtog.org
25
Protocol Amendments
•
All treatment or safety related changes to protocols are amendments,
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Amendments are sent by RTOG to NCI for review and approval.
•
As “Per CTMB Guidelines, amendments must be reviewed and
approved by local IRBs within 90 days.
•
For Canadian sites the broadcast of Health Canada’s approval of the
amendment begins the 90 day timeframe
•
Full board IRB review is required If patients at the site are in active
treatment on the study
•
When using the CIRB, facilitated review by your local IRB may still be
required for all Phase III amendments
www.rtog.org
26
IRB Approvals
• Please review the full content for 45 CFR 46 §46.110 + Category
List from OHRP Website at the following link:
http://ohsr.od.nih.gov/guidelines/45cfr46.html#46.114
www.rtog.org
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MARCH 2012
Drug Procurement
& Accountability
www.rtog.org
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Possible Sources of Drug Supply
•
•
•
•
Pharmaceutical Companies
Third Party Distributor
NCI-Pharmaceutical Management Branch (PMB)
Commercially available products
* More than one may apply in certain studies.
www.rtog.org
29
Canadian Review Board (CRB)
• Purpose: To identify barriers, specifically related to drug
availability and differing RT standards in the various member
provinces early in the development of the protocol when there
is the potential to address these issues.
• Initiated in April 2009
• Representation: a provincial board member from each member
province was appointed by the Canadian vice chair.
• Please remember to share all drug or RT related protocol
concerns with your provincial board member as early as
possible.
www.rtog.org
30
CRB Provincial Representation
& Contact Information
www.rtog.org
31
Important Note About
Non North American Sites
•
Non North American Institutions are advised not to submit a study for
approval by their local regulatory body until their participation has
been confirmed in the written notice of an approved Letter of Intent
(LOI) from RTOG HQ.
•
All Non North American Institutions must submit an LOI to RTOG HQ
indicating their interest in participating in any RTOG Study.
•
Formal Approval of the LOI will be received via e-mail with
IMPORTANT specific instructions for moving forward
•
Once the LOI has been approved, documentation of completion of all
applicable regulatory pre-registration requirements as noted in the
protocol must be submitted directly to the CTSU before enrollment
can begin.
www.rtog.org
32
Important Note About
Non North American Sites
•
Participation will not be possible if any part of the study specific requirements
outlined in the protocol conflict with your country's Ministry of Health
regulations.
•
It is your institution's responsibility to understand and comply with all national
Ministry of Health Regulations.
•
Translation of documents is critical. The cost of all translation would be your
institution's responsibility. All regulatory documents, data and supporting
documentation (when required) would need to be provided in English with
certified/verified translation documentation
•
Your institution will be responsible for acquiring any drug noted in the
protocol as commercially available.
•
Non North American participation in studies with a drug component will only
be permitted if RTOG can procure and provide a supply of the study agent for
your region
www.rtog.org
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International Letter of Intent
(Pages 1& 2 of 3)
www.rtog.org
34
International Letter of Intent
(page 3 of 3)
“****Please review important information attached with response****”.
•
This portion of the form will be
returned to the site by RTOG
HQ noting approval or
disapproval
•
A second very important
document will also be provided
with the approval, entitled
International Letter of Intent to
Participate Response, outlining
expectations and requirements
•
This document must be
retained as a checklist to
assure preregistration
compliance prior to patient
registration/enrollment.
www.rtog.org
35
Finding International Forms
on the Website
• International Letter of Intent (LOI)
www.rtog.org
36
Pharmaceutical Company
Supplied Drug Procurement
• Procedure can vary by study.
• Detailed instructions for obtaining drug can be found
in Section 7.0 of each protocol
• First step a pre-registration requirement, as noted in
Section 5.0, submit the Study Agent Shipment Form
(SASF) to CTSU
• Processing of this form approves the site as eligible
to receive drug
– Registration/Randomization is the trigger for the initial
shipment
www.rtog.org
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SAMPLE (SASF)
Study Agent Shipment Form
www.rtog.org
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Finding RTOG SASFs On the Website
Clinical Trials/Protocol Table/Select Study/Regulatory Resources
www.rtog.org
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Pharmaceutical Company
Supplied Drug Procurement
Submitting your SASF for processing as soon as the
individual responsible for the drug at your institution
has been identified will assist you in:
– avoiding delays in the initial drug shipment
– alleviating frustration and inconvenience for yourself
and most importantly the patient
www.rtog.org
40
Pharmaceutical Company
Supplied Drug Procurement
• Realistic Treatment Start Dates
– If the SASF has already been processed, drug is
received much faster, generally for overnight or two
day delivery.
– Most distributors will not ship prior to a weekend or
holiday.
– Shipments are generally restricted between
December 23 and January 1.
– Canadian sites should take into consideration the
possibility of customs delays
www.rtog.org
41
NCI Drug Procurement
– The Pharmaceutical Management Branch (PMB) of the NCI is
responsible for supplying study agent for studies where the NCI
holds the IND.
– When the PMB supplies the drug for a study they are also
responsible for providing the Investigator Brochure.
– NIH Form 986/Clinical Drug Request is used to order study drug for
NCI sponsored trials
– All NCI Forms are available on the NCI website at
http://ctep.cancer.gov/forms/index.html
• Clinical Drug Request (NIH Form 986)
• Investigational Drug Accountability Record Form (DARF)
• Drug Return
• Drug Transfer
www.rtog.org
42
Canadian Drug Accountability
• There is a PMB approved Canadian Drug Accountability Form,
which can be used by Canadian institutions for both PMB and
pharmaceutically supplied drug.
• This form is available on the RTOG website with the other
Canadian resources
www.rtog.org
43
NCI Drug Procurement
Investigators must be registered with the NCI and have an
Investigator NCI Number to receive drug from the NCI.
Maintenance of this NCI Investigator Number requires the annual
submission of:
– FDA 1572 with CVs
– signed Supplemental Investigator Data Form (IDF)
– Financial Disclosure Form
NCI/PMB Contact Information:
Phone: (301) 496-5725
Fax: (301) 402-0429
www.rtog.org
44
NCI On-Line Drug Procurement
http://ctep.info.nih.gov/branches/pmb/agent_order_processing.htm
www.rtog.org
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Drug Accountability Record Forms
NCI
RTOG
www.rtog.org
46
Finding RTOG Accountability
Records on the Website
Clinical Trials/Protocol Table/Select Study/Regulatory Resources
www.rtog.org
47
Commercially Available Products
• Supplied free of charge through pharmaceutical
support directly from the pharmaceutical
company or via a third party distributor
OR
• Obtained via prescription from the physician
www.rtog.org
48
End of Study Drug Disposition
• Can vary by sponsor/protocol
• Records of accountability documentation may require
submission
– Receipt of Drug
– Dispensation of Drug
– Disposition of Drug (returned/destroyed used/unused)
• Instructions usually documented in the protocol
• Institutional Drug Destruction Policy or SOP
– Required for site drug destruction
www.rtog.org
49
Return/Destruction of Study Drug
• When applicable, unexpired, unused, unopened,
nontransferable agents remaining after a study has been
permanently closed to accrual by RTOG must be returned to
the distributor within 90 days of the RTOG closure broadcast.
• If end of study drug destruction is noted in the protocol it must
be carried out within 90 days of study closure and
accountability records must be retained.
• If the institution lacks a written policy or SOP pertaining to drug
destruction, drug must be returned to the distributor for
destruction within 90 days of study closure.
www.rtog.org
50
Blinded Studies
RTOG saw a marked increase it drug errors on blinded
RTOG studies particularly RTOG 0825.
Please take the time to consider the importance of reviewing drug
administration and safety policies with related staff in an effort to
eliminate these errors.
RTOG suggests a double or even triple check of the drug label
and patient ID or a two person check similar to hospital drug
transfusion policies.
Contact RTOG HQ if you would like assistance with training your
research pharmacy or staff.
www.rtog.org
51
Case & Point
www.rtog.org
52
Blinded Studies
Important Points to remember:
•
The number of RTOG blinded drug studies is increasing.
•
The order of the initials entered during registration significantly
impacts our ability to quickly unblind a case in an emergency situation
•
Initials must be entered as First Middle Last (FML) or F-L if there is no
middle
•
The full DOB (MM/DD/YYYY) is also required for all blinded studies to
allow us to confirm we have the right patient during unblinding in the
event there are cases with the same initials
www.rtog.org
53
Emergency Unblinding Procedures
“Decisions to break the code will only be considered for life threatening
events or extraordinary clinical circumstances where it can be
demonstrated knowledge of the drug treatment assignment will affect
clinical judgment.”
•
During RTOG business hours (8:30AM-5PM ET) call RTOG HQ at 215-574-3150
and ask to speak to a statistician.
•
After hours (5PM-8:30AM ET) call 215-459-3576
•
Calls received after hours or during weekends and holidays will be returned as
soon as possible. Please leave your name, contact information, the first and
last name of the patient who experienced the event, the study & case number
and the reason for the unblinding request.
•
If the unblinding request pertains to RTOG 0825 and tumor progression, please
contact Treena Trotman at 215-940-8913 during regular business hours
www.rtog.org
54
Emergency Unblinding
• Requests to unblind either case in the situation of a corruption
or crossover in drug administration will likely result in both
cases being removed from the study
• The Emergency Unblinding line is for true emergencies only
• Please do not leave messages pertaining to anything but
emergency unblinding
• This is NOT a catch all after hours office line
• Messages left for any other reason will not be forwarded or
receive a response
www.rtog.org
55
Minimum Required Information
for Emergency Unblinding Request
The unblinding officer will contact you for further information.
www.rtog.org
56
Protocol Deviations
• CTEP has a policy in place related to the issuance of waivers
for protocol deviations:
• The policy applies to all components of CTEP-approved
protocols, including eligibility criteria, treatment schedules,
dose modifications, toxicity assessment, response criteria, and
statistical aspects.
• Link to Policy:
http://ctep.cancer.gov/protocolDevelopment/policies_deviation
s.htm
• CTEP does not issue or approve any waivers for protocol
deviations
www.rtog.org
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NCI Deviation Policy
www.rtog.org
58
MARCH 2012
RTOG SAE
Safety Reporting
www.rtog.org
59
NCI Guidelines for AE Reporting
RTOG Data Management is responsible
for and provides basic instruction and NCI based
training and guidance regarding the reporting of
adverse events (AE) and Protocol Specific Special
Reporting (PSSR) via the
Adverse Event Expedited Reporting System (AdEERS)
www.rtog.org
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Current AdEERS Reporting Pathway (Decentralized)
Centralized changes coming soon…
www.rtog.org
61
Centralized SAE Reporting Coming Soon…
www.rtog.org
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The NEW FDA Final Rule
for Expedited Reporting
• The Final Rule:
• 21 CFR Parts 312 and 320 [Docket No. FDA-2000-N-0108]
(formerly Docket No. 00N-1484)
• RIN 0910-AG13
• Investigational New Drug Safety Reporting Requirements for
Human Drug and Biological Products and Safety Reporting
Requirements for Bioavailability and Bioequivalence Studies in
Humans
• http://frwebgate.access.gpo.gov/cgibin/getdoc.cgi?dbname=2010_register&docid=fr29se10-3.pdf
• This regulation requires changes to expedited serious adverse
event reporting requirements for investigators to IND sponsors
such as NCI/CTEP
www.rtog.org
63
Pharmaceutical/Industry
SAE Reporting Requirements
Special considerations when reporting on
pharmaceutically supported studies using the AdEERS
system
• Pharmaceutically supported studies often require additional
reporting over and above that which is required by the NCI.
• Complying with pharmaceutical standards will require
bypassing the “reporting not required” screen in AdEERS and
going on to complete and submit the report.
www.rtog.org
64
SAE Definition
A Serious Adverse Event (SAE) is defined by the Code of Federal
Regulations (CFR) as:
Any untoward medical occurrence that at any dose results in
•
death
•
is life threatening
•
requires inpatient hospitalization or prolongation of existing hospitalization
• results in persistent or significant disability/incapacity
• or is a congenital anomaly/birth defect.
The phrase “at any dose” should be replaced with “during protocol treatment
and 30 days after” for RTOG purposes to capture SAEs that occur during any
part of protocol therapy including radiation therapy or surgery.
Please note reporting outside the 30 day window is required when the event is
determined to be possibly, probably or definitely related to any part of protocol
treatment.
www.rtog.org
65
Important Points
•
Hospitalization is defined as an admission to an inpatient bed for at
least 24 hours.
•
Grade, attribution or expectedness are not a consideration for RTOG
in the reporting of SAEs, simply meeting the criteria in the SAE
definition makes the event an SAE.
•
The use of the CTEP CTCAE Grading Scale instead of the SAE criteria
in the reporting of AEs that may also be considered serious can
become confusing in some instances and allow certain SAEs to go
unreported (e.g., when a patient is hospitalized for a grade 2 event).
•
The new FDA Final Rule RE: Expedited Reporting now also requires all
SAEs be reported unless the protocol states otherwise
www.rtog.org
66
Medically Significant Events
• Medical and scientific judgment should be exercised in
deciding whether reporting as an SAE is appropriate in other
situations, such as important medical events that may not be
immediately life threatening or result in death or hospitalization
but may jeopardize the patient or may require intervention to
prevent one of the outcomes listed in the SAE definition.
• Examples
–
–
–
–
the development of a new malignancy
allergic bronchospasm
blood dyscrasias
convulsions
www.rtog.org
67
Site Initiated
SAE/Safety Reporting
Reporting Serious Adverse Events (SAE)
• AdEERS is the required reporting format for SAEs on all
NCI supported RTOG studies
• A study specific SAE form will be used for upcoming
Foundation Studies (3500 series studies) for transcription
by RTOG into the FDA MedWatch Form
• All events that meet the criteria for an SAE must be
reported regardless of grade or attribution
• SAE/Safety Reporting is separate, and in addition to Data
Management AE reporting (on the CRF)
• All SAEs must be reported to your IRB
www.rtog.org
68
SAE
Serious Adverse Events (SAEs) are defined by FDA and therefore
seriousness (not severity) serves as a guide for defining regulatory
reporting obligations for patient/subject safety. ‘Seriousness’ is based on
patient/event outcome or action criteria usually associated with events
that pose a threat to a patient’s life or functioning. FDA Federal
Regulations require IND sponsors to report serious adverse events via
Expedited reporting.
The two terms “serious” and “severe” are not interchangeable and their
meanings should not be confused.
www.rtog.org
69
24 Hour AdEERS
Notification Requirements
• Phase II & III Studies: hospitalizations grade 4 or > and all grade
4 & 5 events regardless of relationship
• Phase I & early Phase II Studies: hospitalizations grade 3 or >
and all grade 4 & 5 events regardless of relationship
• The timeframe for the complete AdEERS Report associated
with any 24 Hour AdEERS Notifications is 5 days.
• All other SAEs that do not require the submission of a 24 Hour
AdEERS Notification will be reported via AdEERS using the 10
day reporting timeline.
www.rtog.org
70
Foundation Study SAE Report Form
24 Hour Notification Requirements
• Phase II & III Studies: hospitalizations grade 4 or > and all grade
4 & 5 events regardless of relationship
• Phase I & early Phase II Studies: hospitalizations grade 3 or >
and all grade 4 & 5 events regardless of relationship
• The timeframe for the complete Report associated with any
event requiring 24 Hour Notifications is 5 days.
• All other SAEs that do not require the submission of a 24 Hour
Notification will be reported using the 10 day reporting timeline.
www.rtog.org
71
Timelines
• The time frame for submitting the required type of
report will vary from FIVE to TEN CALENDAR DAYS
Please refer to the protocol for specifics
• The day the event is reported is counted as day one.
• The reporting deadline is required to allow for RTOG
and/or pharmaceutical sponsors to fulfill their
external regulatory reporting obligations.
www.rtog.org
72
Table of Timelines
Revised 3/2012 in alignment with centralized reporting & the new FDA Final Rule for Expedited Reporting
www.rtog.org
73
Proper Identification
Proper identification of follow-up or amended reports,
supporting source documentation and/or other information
relevant to the SAE is imperative and must always include
the RTOG study and case number
• Please use the RTOG Case Number as the Patient ID in
the AdEERS System * DO NOT ADD LEADING ZEROS
• Please follow the specific instructions on the SAE Report
Form for Foundation (3500 series) studies
www.rtog.org
74
What type of other documentation must be
submitted with the an SAE Report?
• AdEERS: Only documentation noted by the reporter as being
provided in the additional information section of AdEERS need
be submitted initially
• Foundation (3500 series)SAE Report Form: None unless
specifically requested
• If the pharmaceutical company requires further documentation
or clarification, RTOG will contact you via e-mail with the query/
request
• The NCI may also contact you directly to request specific
information or documentation
www.rtog.org
75
Dedicated SAE Fax Line
215-717-0990
All necessary supporting source documentation relating to the SAE
noted as being supplied in the Additional Information Section of the
AdEERS Report must be properly labeled with the RTOG Study and
Case Number as well as the date and Ticket Number of the
corresponding event and provided within the allotted timeframe or as
soon as it becomes available.
Information pertaining to Foundation (3500 series) Studies must also
be properly labeled with the Study and Case Number as well as the
date of the event
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May 27, 2008
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Guidance and/or Assistance
with the AdEERS System
 It may be helpful to view the AdEERS Tutorial at the following link:
http://ctep.info.nih.gov/reporting/AdEERS_CBT_v3/welcome.html
 Problems or issues with the AdEERS System for reporting AE/SAEs
may also be referred to the following contacts:
 For all medical and policy related issues, please contact the AdEERS
Coordinators by email at [email protected]
<mailto:[email protected]> or telephone (301) 897-7497.
 For all technical and training related issues please contact the NCI
CTEP Help Desk by email at [email protected]
<mailto:[email protected]> or telephone (301)840-8202.
 RTOG AdEERS Coordinator: Sandy McDonald [ [email protected]
or 215-717-0857]
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Guidance and/or Assistance with the
Foundation (3500 series) SAE Report Form
 You can view both the Foundation SAE Report Form and Guidance for
use/completion on the RTOG website www.rtog.org .
 The Foundation SAE Report Form and Guidance are study specific
and will be located under the study specific Regulatory Resources tab
on the website
 The RTOG SAE Coordinator: Sara McCartney[ [email protected] or
267-940-9404 can also provide assistance with using the Foundation
SAE Report Form
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NCI/Pharmaceutical Initiated/External
Safety Reports (ESR)
•
Events detailed in safety reports originating from the NCI or pharmaceutical
company can reference a more global use of the drug
•
These safety reports are intended to inform treating physicians regarding
events that have occurred in the interim that will be included in the next
revised Investigator Brochure
•
No action other than providing these reports to your IRB is required unless
indicated
•
Any questions regarding the overall significance of events reported in these
safety reports should be directed to the NCI or the pharmaceutical company
that initiated the report.
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External Safety Report (ESR) IRB Review
• Local IRB policy can limit the review of ESRs
– Auditors will require a copy of the written IRB policy or SOP
• In the event the Local IRB elects not to review all ESRs
– ESRs must still be reviewed by the PI or designee
– The reviewer should indicate review by signing and dating the report
– All ESRs must still be maintained as part of the study file for review
during a site audit.
• Sites who previously relied on the CIRB review of ESRs for
Phase III studies
– This review is now accomplished by way of review of the RTOG Data
Monitoring Committee (DMC) reports for both Phase IIR & III studies
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Finding Safety Reports on the Website
•
Safety Reports can be found under the study specific broadcasts on the RTOG
website (Clinical Trials > Protocol Table > Study Details > Broadcasts)
•
Safety reports are sent via e-mail broadcast to individuals from participating
institutions who are listed on the RTOG Broadcast List
•
If you would like to be added/removed from the RTOG broadcast list or wish to
update your e-mail address, send a message to [email protected]
•
Sites should not reply directly to any broadcast. Institutions can share a
comment or ask a question by accessing the appropriate department at RTOG
Headquarters on the RTOG web site at www.rtog.org then select the member
information tab and click HQ Information & Telephone Listings. Sites can also
call 1-800-227-5463 ext. 4189, which provides prompts to reach each
department
•
Canadian research staff should be sure to request they be added specifically to
the Canadian Broadcast List to assure the receipt of all broadcast information
relevant to Canadian participation
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Safety Report Broadcasts
Clinical Trials > Protocol Table > Study Details > Broadcasts
www.rtog.org
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On a Lighter Note…
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Regulatory Staff
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