TIP Sheet For Logic Checks To Be Performed in Structural or Coherence Quality Review of SIL - V1.0 - 24 Apr 2020

TIP Sheet for Logic Checks to be performed in Structural/Coherence
Quality Review (QR) of Study Item List (SIL)
Contents
Purpose ......................................................................................................................................................... 2
Target Quality Checks ................................................................................................................................... 2
I. Agreements and Contracts........................................................................................................... 3
II. Vendor Management ................................................................................................................... 4
III. Clinical Study Report .................................................................................................................... 4
IV. Data Management........................................................................................................................ 5
V. IP and Trial Supplies ..................................................................................................................... 7
VI. Protocol and Protocol Amendments ........................................................................................... 8
VII. Investigator Brochure (IB) or Investigational Medicinal Product Dossier (IMPD) or Summary of
Product Characteristics (SmPC)................................................................................................................ 9
VIII. Trial Management ...................................................................................................................... 10
IX. Site Management ....................................................................................................................... 11
X. Safety Reporting ......................................................................................................................... 15
XI. IRB/IEC and Other Approvals ..................................................................................................... 16
XII. Subject Information Sheet (SIS)/Informed Consent Form (ICF) ............................................... 17
XIII. Central and Local Testing .......................................................................................................... 18
XIV. Statistics ...................................................................................................................................... 19
XV. Regulatory .................................................................................................................................. 19
XVI. Translated Documents ............................................................................................................... 20
XVII. TMF Checklists ............................................................................................................................ 21
XVIII. Running Logs............................................................................................................................... 21
XIX. Adhoc SI’s (Correspondence and Note to Files) ........................................................................ 21
_____________________________________________________________________________________
Version 1.0, 24 Apr 2020 Page 1 of 21
Purpose
The intent/focus of these checks is to ensure that all applicable Study Items (SI’s) are present in the
Study Item List (SIL).
Target Quality Checks

Note:
 Any electronic Trial Master File (eTMF) reports should be used only as a tool to document
Quality review (QR) while the actual QR activities should be performed using the eTMF system.
 Please note that the checks listed below are per ICON SOPs. However the ICON eTMF Master
List (GEN007-SOP-A01) column D provides other “Common Alternate Document Names” for all
Document Types listed. This column can be used to perform document mapping in case of
difference in terminologies and accordingly the logic checks listed below can be performed, as
appropriate.
 Checks listed below are to be used as guidance/tips during SIL QR. Other checks may be
performed by the Quality Reviewer as deemed necessary.
 All document types listed in checks below may not be applicable for all studies. Please refer to
Setup tools and/or latest SIL for more information on required document types.
 Please note that the departments added under “Possible Depts. Involved in QR” have been
added via the Document Owner Group/Organization tab (column J) of the eTMF Master List
(GEN007-SOP-A01)
 In case any Missing SI’s are identified during the review, these should be flagged as
discrepancies. The identified missing documents should be filed in the TMF by the study team.
In case the document has not yet been generated, the TMF Lead (TMFL) may be requested to
create the missing SI.
_____________________________________________________________________________________
I. Agreements and Contracts
Possible Depts. Involved in QR: •ClinStdySU, CRAMgt, ClinTrMngmt, FSPProjMgt, PRS
Review eTMF for presence of the following SI’s and check if all required versions/instances of the
documents are filed:
Document Type Comment

Project Contract (225.10) Required for all studies
Note: In some cases this may be filed separately with Contracts
dept.
Contractual Supplier Agreement Required for all vendors contracted by ICON:
(173.10)  ECAC Vendor (Study level)
 ECAC Third Party (Study level)
Note: The list of vendors can be obtained from Project
Management Plan (2.10) or Communication Plan (7.10) or
Vendor Management Plan (2.12).
Confidentiality Agreement – One of these SI’s Should be available for all sites In case of
Investigator (74.10) change in PI where CDA –Investigator (74.10) is present, ensure
Confidentiality Agreement – one SI each is present for both the outgoing and incoming PI.
Institution (74.11)
Clinical Trial Agreement (88.10) Should be available for all applicable investigators for each site
If the PI is a signatory in CTA and there is a change in PI, ensure
one SI each is present for both the outgoing and incoming PI.
Investigator Source Agreement Required for all ICON managed sites.
(99.11)
Investigator Regulatory Agreement Required for all PIs in India & Canada
(85.10) In case of change in PI, a revised document should be available.
Project Management Plan (2.10) Required for all ICON managed studies
Note for TMFL: List of Investigators for a study may be filed in eTMF (under 73.10) or can be extracted
from ICOTrial for purpose of review in ICON managed studies. Responsibility Log (94.10) if filed in eTMF,
can also be used as source for information on site staff including PI.
_____________________________________________________________________________________
II. Vendor Management
Possible Depts. Involved in QR: •FSProjMgt, PRS, ClinTrMgmt
Document Type Comment

Vendor Management Plan (2.12) Ensure required SI’s for each vendor are available
Vendor Meeting Materials (28.11) Note: Not all vendor document types may apply for all vendors
Vendor’s Project Plan (170.11) Note for TMFL: In case of discrepancy in Setup Tool vs current
Vendor’s Manual (170.12) SIL, flag this as issue.
Vendor’s UAT Documentation
(170.13)
Vendor’s Specification
Documentation (170.14)
Vendor’s Validation
Documentation
(170.15)
III. Clinical Study Report
Possible Depts. Involved in QR: •MW &SA, FSProjMgt
Doc ID Document Type Comment

43.10 Clinical Study Report Should be available for all studies.
Multiple SI’s may be present in case of Interim
Study Reports.
43.11 Clinical Study Report Appendices Should be available for all studies.
Multiple SI’s may be present in case of Interim
Study Reports.
_____________________________________________________________________________________
IV. Data Management
Possible Depts. Involved in QR: •ICR DM, FSProjMgt, ClinTrMgmt, IMI
Review the protocol to understand the data collection tools that will be used in the study (e.g.,
Questionnaires, Patient Diaries, etc.). If data collection tools are used, confirm relevant SI’s are present
at the applicable levels.

179.10 Data Management Plan Ensure all versions of the plan are filed
36.10 Final Case Report Form Should be available at study level for all
studies
181.10 Annotated CRF Should be available at study level for all
studies
108.12 TMF Checklist – Data Management Should be available at least at study level for
all studies where ICON DM is contracted.
Note for TMFL: TMFL may refer to the study
File Management Plan or equivalent and
create SI’s based on frequency of QR by the
function
184.15 Core/System specifications Should be available at study level for all
studies where ICON DM is contracted.
184.16 Core/System Specifications QC checklist Should be available at study level for all
Note: This SI may not be applicable if Sponsor
is providing Core/System specifications. In
such cases this SI will usually be fulfilled using
an appropriate reason code & notes.
184.11 Database Specifications Should be available at study level for all
185.11 Database Validation Specification Should be available at study level for all
185.12 Data Validation Specification Issues Log Should be available at study level for all
186.10 Edit Check Validation Plan Should be available at study level for all
187.10 Edit Check Validation Report Should be available at study level for all
187.11 Edit Check Validation Test Scripts Should be available at study level for all
_____________________________________________________________________________________
188.10 Database Release Form Should be available at study level for all
179.13 Listing Specifications Should be available at study level for all
187.15 Listing Programming Validation/Testing Should be available at study level for all
195.13 Listing Validation Sign-Off Form Should be available at study level for all
Post 16 March 2020 this form should be filed
under document ID 187.15.
195.10 DM UAT Plan Should be available at study level for all
195.14 UAT Test Scripts Should be available at study level for all
195.15 UAT Issues Log Should be available at study level for all
195.12 DM UAT Report Should be available at study level for all
195.11 DM UAT Sign-Off and Database Should be available at study level for all
Acceptance Form studies where ICON DM is contracted.
179.12 Data Management Report Should be available at study level for all
193.14 EDC Quality Review Report Should be available at study level for all
Note: Review the Data Management Plan
(DMP) to check no. of Quality Review rounds
required for the study. EDC Quality Review
report should be available for each round of
Quality Review listed in the DMP.
194.10 Database Lock Form Should be available at study level for all
studies
In case of Post Production Change, check for presence of the following:

184.17 Post Production Change Request Form 1 SI should be available at study level for each
PPC.
Note: In case the PPC involves a
major/significant change to Database (this can
be found in the PPC request form), which may
require additional UAT, check for presence of
relevant UAT related SI’s (including UAT Test
Scripts, UAT Report, UAT Sign-Off)
_____________________________________________________________________________________
In case of Data Transfers, check for presence of following:

184.13 Data Transfer Forms One SI should be available for each Data
Transfer.
Cross check the following document types and ensure equal no. of SI’s are present (in studies where
ICON DM is contracted) as mentioned below:
Doc ID Document Type Doc ID Document Type

36.10 Final Case Report Form 36.11 Final CRF Review/Approval Forms
179.13 Listings Specifications 187.15 Listing Programming
Validation/Testing
195.13 Listing Validation Sign-off Form (Post
16 March 2020 this form should be
filed under Doc ID 187.15)
184.17 Post Production Change Request Form 188.10 Database Release Forms (1 DB release
form should be available for each PPC)
In case of changes made to database post DB lock, check for presence of Post Database Lock Change
Form (194.11).
V. IP and Trial Supplies
Possible Depts. Involved in QR: •ClinTrMgmt, FSProjMgt, ClinStdySU, CRAMgt, ITG
For studies that have Investigational Product (IP), confirm that relevant SI’s in table below are present.
Also check if all required versions/instances of the documents are filed:

93.10 IP Release CDP Checklist Should be available for all sites that have been
initiated
112.10 IP Instructions for Handling Should be available as separate document if
these are not covered in Protocol and/or IB
125.10 Certificate of Analysis Should be available for all studies with IP
114.10 IP Documentation of Shipment – Study Should be available if Sponsor requires
IVRS/IWRS data to be uploaded in TMF
- This may be applicable if the Sponsor
does not require individual site level
_____________________________________________________________________________________
shipment documentation to be
uploaded at site level.
- Some Sponsors may require info to be
present on both study and site level.
- TMFL should thus be aware of
Sponsor expectations in this regard.
114.11 IP Documentation of Shipment – Site Should be available for all sites which have
received at least one IP shipment (if
applicable for the study/Sponsor)
115.10 Accountability Documentation – Site Should be available for all sites which have
received IP
120.10 IP Return Tracking Forms and Logs – Study One of these SI’s should be available if IP is
120.11 IP Return Tracking Forms and Logs - Site not destroyed at sites
121.10 Certificate of Drug Destruction – Central Should be available if IP is destroyed Central
Depot
121.11 Certificate of Drug Destruction - Local Should be available if IP destruction is the
responsibility of sites (IP destroyed as per site
SOP)
 Confirm IP Relabeling related SI’s are present if relabeling occurs during the study.
 If IP transfer has occurred ensure relevant SI’s are added.
VI. Protocol and Protocol Amendments
•ClinStdySU, ClinTrMgmt, CRAMgt ,FSProjMgt, MW & SA,

Possible Depts. Involved in QR: IMI
Confirm the following SI’s are present and check if all required versions/instances of the documents are
filed:
Note for TMFL: Review the version history/revision history/summary of changes section of latest version
of Protocol available in eTMF to determine the number of amendments. TMFLs can also use the
information acquired on this during their calls with the study team.

31.10 Protocol Should be available for all studies
33.10 Protocol Amendments All amendments should be filed in eTMF
78.10 Protocol Signature Page Should be available for all initiated sites
- Based on SIV date (found in site
milestone section of Study Home
Page/SIV report), the version of
_____________________________________________________________________________________
protocol initially submitted to the site
may vary. However the TMFL can
verify that the Protocol version which
was effective when the site was
initiated should have been signed off.
79.10 Protocol Amendment Signature Page Should be available for all applicable Protocol
amendments that became effective post-SIV
to the date of site closure (found in site
milestone section of Study Home Page/COV
report).
103.11 Protocol Deviation Criteria template Should be available for all studies
In case ICON is responsible for protocol writing then ensure SI for relevant protocol review and approval
forms for each version are available.
VII. Investigator Brochure (IB) or Investigational Medicinal Product Dossier (IMPD)

or Summary of Product Characteristics (SmPC)
Possible Depts. Involved in QR: •FSProjMgt, ClinTrMgmt, CRAMgt, ClinStdySU, GRA
If a study uses IB or IMPD, all versions of these documents should be filed in the eTMF. At a minimum
these should be revised annually, so check if an updated IB or IMPD is available every year till study
closure. In case no update was made to IB or IMPD for a particular year, a memo or communication
regarding the same should be filed.
In case the comparator used in the study is an approved product then check for SI for Summary of
Product Characteristics (SmPC) – Doc ID 30.12 for all relevant products.
If ICON is contracted for Site Management then:

77.10 Confirmation of IB sent to site One SI for each version of IB that was
effective at the date of SIV to the date of
study closure.
One SI for confirmation of receipt of SmPC for
each approved product/comparator used in
the study.
_____________________________________________________________________________________
VIII. Trial Management
•FSProjMgt, ClinTrMgmt, CRAMgt,ClinStdySU, BioStats, ITG, ICL,

Possible Depts. Involved in QR: MW & SA, PV&SS, MA, A&DMC, ICR DM, TMFOperations, SRG,
IMI, Clinical Risk Management, PRS
Confirm the following SI’s are present and check if all required versions/instances of the documents are
filed:

1.10 File Management Plan Should be available for all studies
Ensure all versions are filed
1.12 Sponsor Translation Requirements Form Should be available for all ICON managed
studies
4.10 List of SOPs current during the Trial Should be available for all studies
7.10 Communication Plan Should be available for all studies
(Where this is an integral part of the PMP
finalized under 2.10 - Project Management
Plan then the Study Item can be fulfilled with
the appropriate reason)
8.10 Monitoring Manual Should be available for all studies
Unblinded monitoring manual (if applicable)
should also be filed under this doc ID.
If centralized monitoring is contracted, then
check for presence of ICONIK Patient Centric
Monitoring (IPCM) Toolkit under this doc ID.
11.13 Investigator Ethics Compliance Post September 2016, this Doc ID should be
Documentation - Study available for all studies where ICON is
responsible for Site Management.
Prior to September 2016, Doc ID 11.11 –
“Ethics and compliance acknowledge
certification (ECAC)” should be available for
all PIs if ICON is responsible for Site
Management.
15.10 Project Team Contact List Should be available for all studies
108.10 TMF Checklist – Project Management Should be available for all studies where
Project Management is contracted to ICON
Note for TMFL: Integrated Quality & Risk Management plan (IQRMP) will list all applicable plans for a
study. All versions of each plan listed on this should be available in the TMF.
_____________________________________________________________________________________
In case the study had an Investigator Meeting (this information may be found in Study Setup Tool), the
following SI’s should be available:
Doc ID Document Type

25.10 Investigator Meeting Agenda
25.11 Investigator Meeting Materials
25.12 Investigator Meeting Attendance Documentation
Review the protocol to ascertain if the study utilizes an Independent Data Monitoring Committee
(DMC/DSMB), Endpoint Adjudication Committee or Other (non-IDMC) Trial Committee, please check
that the relevant corresponding SI’s are also available.
In addition, if Adjudication & DMC Management is contracted to ICON then, ensure the presence of
below SI’s:

108.20 TMF checklist - Adjudication and DMC Management
IX. Site Management
•FSProjMgt, ClinTrMgmt, CRAMgt, ClinStdySU, Clinical Risk

Possible Depts. Involved in QR: Management, IMI, PRS, MA
Check for the presence of following SI’s (where ICON is contracted for Site Management and Monitoring
activities) and check if all required versions/instances of the documents are filed:

101.10 Site Visit Log Should be available for all sites
75.14 Site Selection Confirmation Should be available for all selected sites
Note: This may not be available/might be
combined with PSV followup letter in case
the site selection has been completed by
the Sponsor.
80.10 CV – Principal Investigator Should be available for all PIs
Note:
- In case of change in PI, this should
be available for both the incoming
as well as outgoing PI.
- Depending on Sponsor
expectation, updated CVs may be
_____________________________________________________________________________________
required to be filed after a pre-
defined interval.
81.10 CV – Sub-Investigator Should be available for all Sub-Investigators
(SIs) listed in the Responsibility Log and/or
FDA 1572.
Note:
- In case of change in SI, this should
be available for both the incoming
as well as outgoing SI.
- Depending on Sponsor
expectation, updated CVs may be
required to be filed after a pre-
defined interval.
83.10 GCP or local Regulations Training Certificate Should be available for PI as well as all SIs
83.12 Medical License listed in the Responsibility Log and/or FDA
1572 (subject to Sponsor/Country
requirements)
Note:
- This document is subject to
Sponsor requirements. Some
Sponsors may not require this
document to be filed if GCP
training and/or prior clinical trial
experience & Medical
license/registration number is
captured in CVs.
- Some Sponsors may require an
updated GCP certificate and
Medical License/Registration to be
filed upon expiry.
- It is recommended that Sponsor
expectations are confirmed during
study setup phase.
84.10 Form FDA 1572 Should be available for all PIs for US
Note:
- Not applicable for
Observational/Non-interventional
studies/Non-IND studies
- Sponsor expectations may vary in
case of non-US countries, where at
times an alternative form/template
to FDA 1572 may be required to be
completed e.g. ICH GCP
Compliance Form
- In case of change in PI, applicable
document should be available for
_____________________________________________________________________________________
both the incoming as well as
outgoing PI.
86.10 Financial Disclosure Forms Should be available for PI as well as all SIs
listed in the Responsibility Log and FDA
1572.
Note:
- Not applicable for
Observational/Non-interventional
studies/Non-IND studies
87.10 Site Data Protection Consent Form (SDPCF) Should be available for PI as well as all SIs
listed in the Responsibility Log and FDA
1572.
94.10 Site Responsibility Log Should be available for all initiated sites.
Note:
- Generally in case of change in PI, a
separate log is available for
outgoing and incoming PIs.
However this may vary from
Sponsor to Sponsor.
- Since this is an incremental
document hence this log is filed as
a versioned document, during the
course of study.
97.10 Site Training Documentation Should be available for all initiated sites
Note:
- In case an eTraining Portal (e.g.
Firecrest) are used to capture site
trainings, this SI may not be
applicable. Instead the Firecrest
Training Logs should be filed under
Doc ID 97.11 – “Site Training
Documentation – Study”.
98.10 Screening and Enrollment Log Should be available for all initiated sites
98.11 ICF Log Should be available for all initiated sites
99.10 Electronic Source Data Integrity Should be available for all initiated sites
Questionnaire
99.11 Investigator Source Agreement Should be available for all initiated sites
Note for TMFL: For Site level running logs – refer to the Monitoring Manual to determine if ongoing logs
are to be collected and filed in the TMF.
_____________________________________________________________________________________
For each site visit, confirm that a confirmation, report & follow up letter is available:
Visit Type Required Document Types per Visit

Pre-Study Visit 76.10 – Pre-Study Visit Confirmation
76.11 – Pre-Study Visit Report
76.12 – Pre-Study Visit Follow Up Letter
Note: where ICON is responsible for site selection & PSVs, Site
Selection Confirmation (75.14) may be sent to sites separately, if not
combined with PSV follow up letter (76.12)
Site Initiation Visit 95.11 – Site Initiation Visit Confirmation
95.10 – Site Initiation Visit Report
95.20 – Site Initiation Visit Follow Up Letter
Site Monitoring Visit 100.12 – Monitoring Visit Confirmation
100.10 – Monitoring Visit Report
100.11 – Monitoring Visit Follow Up Letter
Site Close-Out Visit 105.12 – Close Out Visit Confirmation
105.10 – Close Out Visit Report
105.11 – Close Out Visit Follow Up Letter
Other Site Visit (e.g. Three SI’s for Other Site Visit Type(s) Documentation (102.10) are
Motivational Visit, required, one each to file:
Pharmacy Visit) - Confirmation Letter
- Report
- Follow Up Letter
Note:
1. Any attachments to the Confirmation or Follow-up Letters should have been filed separately in
appropriate SI.
2. Ensure all documents for non-selected countries/sites are filed appropriately in Doc ID 75.16 and
75.13.
Note for TMFL: Visit related information can be extracted from ICOTrial via Monitoring Visit Raw Data
Report.
_____________________________________________________________________________________
X. Safety Reporting
•FSProjMgt, PV&SS, MA, GRA, SRG, MW&SA,ClinTrMgmt,

Possible Depts. Involved in QR: CRAMgt, A&DMC
In studies where ICON is contracted for Pharmacovigilance and Safety Services (PVSS), confirm the
presence for following SI’s and check if all required versions/instances of the document are filed:

143.10 SAE/Pregnancy Management Plan Should be available for all studies
143.11 Medical Safety Management Plan Should be available for all studies
145.13 CIOMS Report Should be available for all studies based on
145.14 MedWatch Report participating countries as applicable
145.10 SUSAR/SUA Reports Note:
- Safety Reports (SUSAR/SUA ,
MedWatch & CIOMS) may or may
not be available for every study
- MedWatch reports are distributed
in US & Puerto Rico while CIOMS
reports are distributed in Rest of
the World
146.14 SAE Report Template Should be available for all studies (except
Non-interventional studies)
106.10 Notification to Investigators of Safety One of these SI’s should be present per
Information – Country Safety Report (CIOMS/MedWatch/SUSAR)
106.11 Notification to Investigators of Safety
Information – Site
106.12 Notification to Investigators of Safety
Information - Study
Note: Safety reports and their distribution should be applicable for all studies.
In case PEGA-eTMF Integration is being used for the study, then safety reports
(CIOMS/SUSRAs/MedWatch) will be generated and filed in eTMF only at the study level (no site level
docs will be available). No site specific details will be incorporated in the additional information of this
study level document. Documents coming from the integration will be reviewed by SRG team in eTMF.
Note: Due to filing of documents via integration, additional information of multiple docs may be similar
however these may not necessarily be duplicates. This is because docs are being generated at site level
but filed at study level and may not have any site specific/PI identifier to differentiate them. In these
cases confirm that the documents are being submitted via eTMFPEGA@iconplc.com. In case a similar
document with specific additional info (per Master List requirement) is manually submitted then this
may be a duplicate.
_____________________________________________________________________________________
Note for TMFL: The TMFL may not be able to view the content of docs filed by PEGA-eTMF integration if
these have been indexed as unblinded docs (even though the study may be an open label study).
However they will still be able to view the SI for the docs filed.
In cases where PVSS is responsible for data reviews, check for the presence of following SI’s:

143.13 Laboratory/Diagnostic Test Report Review
143.14 Safety or Medical Data Review
XI. IRB/IEC and Other Approvals
Possible Depts. Involved in QR:

•ClinStdySU, CRAMgt, FSProjMgt, ClinTrMgmt
 SSU to reconcile and confirm that all docs from ACTIVATE have been filed in TMF.
 For each IRB/IEC, confirm that SI’s are present for the following document types at appropriate
level(s) (e.g. Country and/or Site level):
- IRB/IEC Membership List
- IRC/IEC GCP compliance statement
- IRB/IEC submission(s) and corresponding approval(s) - (Note: Submissions may not be
applicable for certain IRB/IECs or for all Sponsors)
 All sites must be IRB/IEC approved. An IRB/IEC may oversee some or all sites within a country (e.g.
central/national/regional) or specific site or sites (e.g. local). Some sites may have both country and
local IRB/IECs.
 At a minimum, IRB/IEC Approval to participate should be present for all initiated sites at the
appropriate level(s).
 All IRB/IECs must receive notification of safety information. If there are Safety Notifications
(SUSARs/CIOMs/MedWatch) available, confirm that correct SI’s are present at appropriate level(s).
 In case PEGA-eTMF integration is being used in the study, the IRB/IEC notification letter for safety
reports may be filed at study level in eTMF along with other docs from PEGA system. In this case
confirm that acknowledgements received from the IRB/IEC, (if applicable) are filed at appropriate
level(s).
_____________________________________________________________________________________
XII. Subject Information Sheet (SIS)/Informed Consent Form (ICF)

•ClinStdySU, CRAMgt, FSProjMgt, ClinTrMgmt
In general a study should have SI’s for all levels of SIS/ICF with the exception of single country/single site
studies along with their Version Tracking Logs and Checklists. If a protocol amendment resulted in an
update to SIS/ICF, confirm another set of SI’s is present.

39.10 SIS/ICF Global Master Template
39.17 SIS/ICF Checklist Global Master
39.14 SIS/ICF Version Tracking Log Global Master
39.11 SIS/ICF Regional Master Template
39.21 SIS/ICF Checklist Regional Master
39.20 SIS/ICF Version Tracking Log Regional Master
39.12 SIS/ICF Country Master
39.18 SIS/ICF Checklist Country Master
39.15 SIS/ICF Version Tracking Log Country Master
39.13 SIS/ICF – Site
39.19 SIS/ICF Checklist – Site
39.16 SIS/ICF Version Tracking Log – Site
 In case of translations and back-translations of ICFs, appropriate attributes/metadata to indicate

the same should be available. Each translation and back translation of the ICF should be listed in
ICF checklists filed at appropriate level(s).
 A single ICF Checklist study item may be appropriate to cover multiple versions of the ICF for a
site if it is fulfilled with reason code [“Document Part of Other Document – Filed to Other
Document Placeholder”] in case the checklists were completed at country level for site level ICFs
that only have site information customization.
 Review the Sponsor Translation Requirements Form (1.12) where applicable to understand the
document translation requirements of the study.
_____________________________________________________________________________________
XIII. Central and Local Testing

•ClinStdySU, CRAMgt, FSProjMgt, ClinTrMgmt, ICL
The protocol should be reviewed to determine if any Central Labs are being used in the trial. Confirm SI’s
for following document types are present for each lab and check if all required versions/instances of the

153.10 Central laboratory Accreditation, Lab Not required for Bioanalytical Labs
Certificate
156.10 Central Lab – Reference Ranges Ensure all versions are filed.
Not required for Bioanalytical Labs
157.10 Central lab – Manual Ensure all versions are filed.
Required for most central diagnostic labs
159.10 Central lab - Director CV Required for all Central labs
Note: Sometimes this may be a part of Lab
Manual and hence in such cases SI may not
be applicable
In case Centralized Bioanalytical Labs are being used in the study, confirm that the below SI’s are also
present:

155.10 Central lab – Bioanalytical Documentation
154.10 Central Lab – Bioanalytical Validation Documentation
In case ICON Labs is used for the study, then check for SI of Central Lab Worksheets (CLW) – 157.11.
In case of sample retention please confirm that SI for Central lab - Record of Retained Body Fluids /
Tissue Samples (165.10) is available.
At site level confirm the presence of SIs for Lab shipment records
Note for TMFL:
 In addition, also confirm the applicable SI’s are present as defined in the Setup Tool.
_____________________________________________________________________________________
XIV. Statistics
•Biostats, FSProjMgt, A&DMC, CRAMgt, ICR DM, MW&SA

Confirm the SI’s for following document types are present for all studies where ICON has been
contracted for Biostatistics & Programming (BS&P), as applicable and check if all required
versions/instances of the document are filed:

200.10 Statistical Analysis Plan Should be available for all studies
201.10 Randomization Plan Should be available for all randomized
studies
206.10 Randomization Release Request Form Should be available for all randomized
studies (except open label randomized
studies)
127.10 Unblinding Plan Should be available for all blinded studies
206.11 Sponsor Approval of Unblinding Should be available for all blinded studies
216.10 Final Analysis Outputs Should be available for all studies
219.10 Final Statistical Report Should be available for all studies
219.11 Final Statistical Report Review Documentation Should be available for all studies
In case an Interim Analysis is planned for the study, confirm all the relevant SI’s for the same are
available.
XV. Regulatory
•Biostats, FSProjMgt, A&DMC, CRAMgt, ICR DM, MW&SA,

Possible Depts. Involved in QR: ClinTrMgmt
Confirm the SI’s for following document types are present for all countries involved in the study and
check if all required versions/instances of the documents are filed:

46.10 Regulatory Authority Submission – Country Should be available for all countries
47.10 Regulatory Authority Approval – Country Should be available for all countries
46.11 Regulatory Authority Submission – Site Should be available for all applicable sites
47.11 Regulatory Authority Approval – Site Should be available for all applicable sites
 Ensure that all Regulatory Authority related docs have been reconciled with those present in
ACTIVATE.
_____________________________________________________________________________________
 If there is no approval provided, the relevant SI should be present and fulfilled with appropriate
reason code.
 If a study is conducted in US or EU, the notification of IND or EudraCT number to Regulatory
Authority at country level should be filed under Regulatory Authority Notification of Identification
Number – Country (48.10).
 For public registrations on ClinicalTrials.gov, the documentation may be filed under Public
registration (49.10).
 In order to gain more knowledge about Country specific Regulatory Requirements, Quality Reviewer
can refer to Regulatory Intelligence Veeva Vault (to gain access to this system complete OLL
G50171).
XVI. Translated Documents
During the startup phase of all ICON studies, a Sponsor Translation Requirements form is signed. The
purpose of this form is to delineate Sponsor expectations for translations and/or back-translations of
trial related documents.
In case of translated documents please confirm the presence of following documents for each
translation performed:
 Original (or Source of translation) document

 Translated Document (with correct attributes/metadata)
 Translation and Proofreading Certificate
In case, back-translations are applicable, below documents should also be available:
 Back-Translated Document (with correct attributes/metadata)

 Translation and Proofreading Certificate
Note:
1. In case the translation/back-translation is done externally (outside ICON), then a Translation and
Proof Reading Certificate should be available. However in case of translations/Back-translations
performed within ICON, two SI’s will be available – one for Translation Certificate and other for
Proofreading Certificate.
2. If a document is translated or back-translated from a study level master (source) document
without any customization then this should be filed at study level. E.g. a Venezuela - Spanish
translation of study level patient diary (English), should be filed at study level (and not at
country level in Venezuela).
_____________________________________________________________________________________
XVII. TMF Checklists
Each organization and/or category listed in ICOMaster Master List (GEN007-MAN001-GD001), there is a
SI for filing TMF Checklist. It is recommended that the Quality Reviewer reviews the study File
Management Plan to understand the TMF QR requirements and then reviews the
implementation/compliance to these requirements (with regards to QR frequency) while performing SIL
QR. TMFLs may create additional TMF Checklist related SI’s based on the review of FMP.
XVIII. Running Logs
All running logs should be filed as versions in the same SI. For all site level running logs, please refer to
the Monitoring Plan to determine if these are required to be collected and filed on an ongoing basis.
XIX. Adhoc SI’s (Correspondence and Note to Files)
Filter the eTMF extract to ascertain that no adhoc SI has been fulfilled with a reason or is empty. In case
any such instances are identified, flag these as findings.
Volume of Note to Files (NTFs) can be monitored by Quality Reviewer during QRs to flag high number of
NTFs during ongoing reviews. This is important as high number of NTFs indicates lack of inspection
readiness and hence has been flagged as finding during audits and Regulatory Inspections.
It is also suggested to review a sample of NTFs (at all levels) to ensure that the content of NTFs being
filed in the TMF is appropriate. This will help in determining and removing any unnecessary NTFs.
_____________________________________________________________________________________

TIP Sheet For Logic Checks To Be Performed in Structural or Coherence Quality Review of SIL - V1.0 - 24 Apr 2020

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TIP Sheet For Logic Checks To Be Performed in Structural or Coherence Quality Review of SIL - V1.0 - 24 Apr 2020

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TIP Sheet for Logic Checks to be performed in Structural/Coherence

Quality Review (QR) of Study Item List (SIL)

Target Quality Checks

I. Agreements and Contracts

Possible Depts. Involved in QR: •ClinStdySU, CRAMgt, ClinTrMngmt, FSPProjMgt, PRS

Document Type Comment

II. Vendor Management

Possible Depts. Involved in QR: •FSProjMgt, PRS, ClinTrMgmt

Document Type Comment

III. Clinical Study Report

Possible Depts. Involved in QR: •MW &SA, FSProjMgt

Doc ID Document Type Comment

IV. Data Management

Possible Depts. Involved in QR: •ICR DM, FSProjMgt, ClinTrMgmt, IMI

Doc ID Document Type Comment

In case of Post Production Change, check for presence of the following:

Doc ID Document Type Comment

In case of Data Transfers, check for presence of following:

Doc ID Document Type Comment

Doc ID Document Type Doc ID Document Type

V. IP and Trial Supplies

Possible Depts. Involved in QR: •ClinTrMgmt, FSProjMgt, ClinStdySU, CRAMgt, ITG

Doc ID Document Type Comment

VI. Protocol and Protocol Amendments

•ClinStdySU, ClinTrMgmt, CRAMgt ,FSProjMgt, MW & SA,

Doc ID Document Type Comment

VII. Investigator Brochure (IB) or Investigational Medicinal Product Dossier (IMPD)

Possible Depts. Involved in QR: •FSProjMgt, ClinTrMgmt, CRAMgt, ClinStdySU, GRA

If ICON is contracted for Site Management then:

Doc ID Document Type Comment

VIII. Trial Management

•FSProjMgt, ClinTrMgmt, CRAMgt,ClinStdySU, BioStats, ITG, ICL,

Doc ID Document Type Comment

Doc ID Document Type

Doc ID Document Type

IX. Site Management

•FSProjMgt, ClinTrMgmt, CRAMgt, ClinStdySU, Clinical Risk

Doc ID Document Type Comment

Visit Type Required Document Types per Visit

•FSProjMgt, PV&SS, MA, GRA, SRG, MW&SA,ClinTrMgmt,

Doc ID Document Type Comment

Doc ID Document Type

XI. IRB/IEC and Other Approvals

Possible Depts. Involved in QR:

XII. Subject Information Sheet (SIS)/Informed Consent Form (ICF)

Possible Depts. Involved in QR:

Doc ID Document Type

 In case of translations and back-translations of ICFs, appropriate attributes/metadata to indicate

XIII. Central and Local Testing

Possible Depts. Involved in QR:

Doc ID Document Type Comment

Doc ID Document Type

Note for TMFL:

•Biostats, FSProjMgt, A&DMC, CRAMgt, ICR DM, MW&SA

Doc ID Document Type Comment

•Biostats, FSProjMgt, A&DMC, CRAMgt, ICR DM, MW&SA,

Doc ID Document Type Comment

XVI. Translated Documents

 Original (or Source of translation) document

In case, back-translations are applicable, below documents should also be available:

 Back-Translated Document (with correct attributes/metadata)

XVII. TMF Checklists

XVIII. Running Logs