M11 TECHNICAL SPECIFICATION: 
CLINICAL ELECTRONIC 
STRUCTURED HARMONISED 
PROTOCOL  
(CESHARP) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
Administration (FDA or Agency) on this topic.  It does not establish any rights for any person 
and is not binding on FDA or the public.  You can use an alternative approach if it satisfies the 
requirements of the applicable statutes and regulations.  To discuss an alternative approach, 
contact the FDA staff responsible for this guidance as listed on the title page.  The draft guidance 
has been left in the original International Council for Harmonisation format.  The final guidance 
will be reformatted and edited to conform with FDAs good guidance practice regulation and 
style. 
 
 
 
 
 
 
  
 
 
For questions regarding this draft document, contact (CDER) Veronica Pei, 240-402-7091, 
Veronica.Pei@fda.hhs.gov.  
  
  
  
   
 
  
FOREWORD  
  
The International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) has the mission of achieving greater regulatory 
harmonization worldwide to ensure that safe, effective, and high-quality medicines are 
developed, registered, and maintained in the most resource-efficient manner.  By 
harmonizing the regulatory expectations in regions around the world, ICH guidelines 
have substantially reduced duplicative clinical studies, prevented unnecessary animal 
studies, standardized safety reporting and marketing application submissions, and 
contributed to many other improvements in the quality of global drug development and 
manufacturing and the products available to patients.   
  
ICH is a consensus-driven process that involves technical experts from regulatory 
authorities and industry parties in detailed technical and science-based harmonization 
work that results in the development of ICH guidelines.  The commitment to consistent 
adoption of these consensus-based guidelines by regulators around the globe is critical 
to realizing the benefits of safe, effective, and high-quality medicines for patients as 
well as for industry.  As a Founding Regulatory Member of ICH, the Food and Drug 
Administration (FDA) plays a major role in the development of each of the ICH 
guidelines, which FDA then adopts and issues as guidance to industry. 
   
   
 
 
 
 
INTERNATIONAL COUNCIL FOR HARMONISATION OF TECHNICAL 
REQUIREMENTS FOR PHARMACEUTICALS FOR HUMAN USE 
 
 
 
 
 
ICH HARMONISED GUIDELINE 
 
 
 
 
 
CLINICAL ELECTRONIC STRUCTURED HARMONISED 
PROTOCOL 
(CESHARP) 
 
M11 TECHNICAL SPECIFICATION 
 
 
 
 
Draft version 
 
Endorsed on 27 September 2022 
 
Currently under public consultation 
 
 
 
 
 
 
 
At Step 2 of the ICH Process, a consensus draft text or guideline, agreed by the appropriate 
ICH Expert Working Group, is transmitted by the ICH Assembly to the regulatory authorities 
of the ICH regions for internal and external consultation, according to national or regional 
procedures. 
   
 
M11 Technical Specification 
Document History 
 
Code  History  Date 
M11  Endorsement by the Members of the ICH Assembly  27 September 
under Step 2 and release for public consultation  2022 
(document dated 6 September 2022). 
Minor editorial changes made pre-publication (document 
dated 14 October 2022). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Legal notice: This document is protected by copyright and may, with the exception of the ICH 
logo, be used, reproduced, incorporated into other works, adapted, modified, translated or 
distributed  under  a  public  license  provided  that  ICH's  copyright  in  the  document  is 
acknowledged at all times. In case of any adaption, modification or translation of the document, 
reasonable steps must be taken to clearly label, demarcate or otherwise identify that changes 
were  made  to  or  based  on  the  original  document.  Any  impression  that  the  adaption, 
modification or translation of the original document is endorsed or sponsored by the ICH must 
be avoided.  
The document is provided "as is" without warranty of any kind. In no event shall the ICH or 
the authors of the original document be liable for any claim, damages or other liability arising 
from the use of the document.  
The above-mentioned permissions do not apply to content supplied by third parties. Therefore, 
for documents where the copyright vests in a third party, permission for reproduction must be 
obtained from this copyright holder.    
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1  Technical Specification 
2  The purpose of this document is to serve as a technical representation of the ICH M11 
3  protocol template. This Technical Specification (TS) is to be aligned with the latest version of 
4  the ICH M11 Guideline and protocol template, but with flexibility in addressing data 
5  exchange needs per ICH and those of regional authorities.   
6  NOTE:  Following the public comment period, the M11 Guideline and template may be 
7  updated along with the Technical Specification.  The M11 EWG recognises that the Technical 
8  Specification is at an early stage of maturity as certain terms (variables) in this version (e.g., 
9  Cardinality, Definition, Relationship to Conceptual Model) are to be addressed post the public 
10  comment period and as the M11 EWG progresses through the ICH Step process. 
11  Appendix 1: Detailed Descriptions of Information Components  
12  Overall Rules 
Term (Variable)  Overall rules 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Rules 
Cardinality   
Relationship content  All document 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  REQUIRED Level 1 and Level 2 headings 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
 
Duplicate field in   
other sections 
13   
Page 5 of 346 
   
14  0.  Foreword 
Term (Variable)  Foreword 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section heading 
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  0. Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Foreword 
Business rules  Value Allowed: Yes 
Relationship: Not transferred 
Concept: Protocol title 
Duplicate field in   
other sections 
15  0.1  Template Revision History 
Term (Variable)  Template Revision History 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section heading 
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Template Revision History 
Business rules  Value Allowed: Yes 
Relationship: Not transferred 
Concept: Protocol title 
Duplicate field in   
other sections 
16   
Page 6 of 346 
   
Term (Variable)  Date 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Table column heading 
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Date 
Business rules  Value Allowed: Yes 
Relationship: Table column heading 
Concept: n/a 
Duplicate field in   
other sections 
17   
Term (Variable)  Date of Revision 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Date of Revision 
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Date 
Business rules  Value Allowed: Yes 
Relationship: Repeating for each new date 
Not transferred  
Concept: n/a 
Duplicate field in   
other sections 
18   
Page 7 of 346 
   
Term (Variable)  Description of Revision 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Table column heading 
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Table column heading 
Business rules  Value Allowed: Yes 
Relationship: Table column heading 
Not transferred  
Concept: n/a 
Duplicate field in   
other sections 
19   
Term (Variable)  Description of Revision 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Description of Revision 
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Description of revision text 
Business rules  Value Allowed: Yes 
Relationship: Repeating for each description of revision 
Not transferred  
Concept: n/a 
Duplicate field in   
other sections 
20   
Page 8 of 346 
   
21  0.2  Intended Use of Template 
Term (Variable)  Intended Use of Template 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section heading 
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Intended Use of Template 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
22   
Term (Variable)  Intended Use of Templates 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Section heading 
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Intended Use of Template 
Business rules  Value Allowed: Yes 
Relationship: Not transferred 
Concept: n/a 
Duplicate field in   
other sections 
23   
Page 9 of 346 
   
24  0.3  Template Conventions and General Instruction 
Term (Variable)  Template Conventions and General Instruction 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section heading 
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  0.3 Template Conventions and General Instruction 
 
Business rules  Value Allowed: Yes 
Relationship: Not transferred 
Concept: n/a 
Duplicate field in   
other sections 
25   
Term (Variable)  Description of Conventions 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Explains conventions and general instruction 
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Description of conventions 
Business rules  Value Allowed: Yes 
Relationship: Not transferred 
Concept: n/a 
Duplicate field in   
other sections 
26   
Page 10 of 346 
   
Term (Variable)  Description of conventions 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Explains conventions and general instruction 
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: Not transferred 
Concept: n/a 
Duplicate field in   
other sections 
27   
Term (Variable)  Heading Structure and Flexibility 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Heading structure and flexibility 
 
Business rules  Value Allowed: Yes 
Relationship: Not transferred 
Concept: n/a 
Duplicate field in   
other sections 
28   
Page 11 of 346 
   
Term (Variable)  Heading Structure and Flexibility 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: Not transferred 
Concept: n/a 
Duplicate field in   
other sections 
29   
Term (Variable)  Table and Figure Numbering 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Table and figure numbering 
Business rules  Value Allowed: Yes 
Relationship: Not transferred 
Concept: n/a 
Duplicate field in   
other sections 
30   
Page 12 of 346 
   
Term (Variable)  Table and Figure Numbering 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: Not transferred 
Concept: n/a 
Duplicate field in   
other sections 
31   
Term (Variable)  Terminology 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Terminology 
Business rules  Value Allowed: Yes 
Relationship: Not transferred 
Concept: n/a 
Duplicate field in   
other sections 
32   
Page 13 of 346 
   
Term (Variable)  Terminology 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: Not transferred 
Concept: n/a 
Duplicate field in   
other sections 
33   
Term (Variable)  Suggestion for Publishing a Paper or PDF Document 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Suggestion for publishing a paper or PDF document 
Business rules  Value Allowed: Yes 
Relationship: Not transferred 
Concept: n/a 
Duplicate field in   
other sections 
34   
Page 14 of 346 
   
Term (Variable)  Suggestion for Publishing a Paper or PDF Document 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: Not transferred 
Concept: n/a 
Duplicate field in   
other sections 
35   
Term (Variable)  Abbreviations Used in this Template 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Abbreviations Used in this Template 
Business rules  Value Allowed: Yes 
Relationship: Not transferred 
Concept: n/a 
Duplicate field in   
other sections 
36   
Page 15 of 346 
   
Term (Variable)  Abbreviations Used in this Template 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Not required 
Cardinality   
Relationship content  Foreword 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: Not transferred 
Concept: n/a 
Duplicate field in   
other sections 
37  Protocol Full Title 
Term (Variable)  Protocol Full Title 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Protocol Full Title 
Business rules  Value Allowed: Yes 
Relationship: Table row heading 
Concept: n/a 
Duplicate field in   
other sections 
38   
Page 16 of 346 
   
Term (Variable)  Protocol Full Title 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  The protocol should have a descriptive title that identifies the scientific 
aspects of the trial sufficiently to ensure it is immediately evident what 
the trial is investigating and on whom, and to allow retrieval from 
literature or internet searches. 
Conformance  Required  
Cardinality   
Relationship content  Title page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  4000 Eudra characters    
600 ct.gov 
UTF 8  -  Special 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: Protocol Title 
Duplicate field in   
other sections 
39   
Term (Variable)  Sponsor Confidentiality Statement 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Sponsor confidentiality statement 
Business rules  Value Allowed: Yes 
Relationship: Table row heading 
Concept: n/a 
Duplicate field in   
other sections 
40   
Page 17 of 346 
   
Term (Variable)  Sponsor Confidentiality Statement 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Insert a sponsor confidentiality statement, if applicable, otherwise 
delete. 
Conformance  Optional 
Cardinality   
Relationship content  Title page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
41   
Term (Variable)  Protocol Number 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Protocol number 
Business rules  Value Allowed: Yes 
Relationship: Table row heading 
Concept: n/a 
Duplicate field in   
other sections 
42   
Page 18 of 346 
   
Term (Variable)  Protocol Number 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  A unique alphanumeric identifier for the trial. 
User Guidance  A unique alphanumeric identifier for the trial, designated by the sponsor, 
is a standard part of trial data, and should be included for most studies.  
Some exceptions may exist, however, so this is an optional field. 
Conformance  Required  
Cardinality   
Relationship content  Title page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  AN 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: Protocol identifying number 
 
Note:  May be blank (null) 
Duplicate field in   
other sections 
43   
Term (Variable)  Version 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Version 
Business rules  Value Allowed: Yes 
Relationship: Table row heading 
Concept: n/a 
Duplicate field in   
other sections 
44   
Page 19 of 346 
   
Term (Variable)  Version 
Data Type  Number 
Topic, Value or  D 
Header 
Definition   
User Guidance  An optional field for use by the sponsor at their discretion. 
Conformance  Optional  
Cardinality   
Relationship content  Title page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  10N 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: Amendment number 
Duplicate field in   
other sections 
45   
Term (Variable)  Amendment Number 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Title page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Amendment Number 
Business rules  Value Allowed: Yes 
Relationship: Table row heading 
Concept: n/a 
Duplicate field in   
other sections 
46   
Page 20 of 346 
   
Term (Variable)  Amendment Number 
Data Type  Number 
Topic, Value or  D 
Header 
Definition   
User Guidance  Enter the version, number, or amendment number.  If this is the original 
instance of the protocol, indicate Not Applicable. 
Conformance  Conditional 
Cardinality   
Relationship content  Title page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  10N 
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: Amendment number 
Duplicate field in   
other sections 
47   
Term (Variable)  Amendment Scope 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Amendment Scope 
Business rules  Value Allowed: Yes 
Relationship: Table row heading 
Concept: n/a 
Duplicate field in   
other sections 
48   
Page 21 of 346 
   
Term (Variable)  Amendment Scope 
Data Type  Pick list 
Topic, Value or  D 
Header 
Definition   
User Guidance  Acceptable entries for amendment scope are:  Global or Country-
specific/Regional 
Conformance  Required  
Cardinality   
Relationship content  Title page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Global or Country-specific/Regional 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
49   
Term (Variable)  Country/Region or Local Identifier 
Data Type  Pick list 
Topic, Value or  D 
Header 
Definition   
User Guidance  Use the ISO-3166 region or local identifier (i.e., DE or EU). For global 
trials delete the Region or Local Identifier field. 
Conformance  Required/Conditional 
Cardinality   
Relationship content  Title page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  ISO 3166 for country and region blank for global 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeatable 
other sections 
50   
Page 22 of 346 
   
Term (Variable)  Compound Number(s) 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Compound Number 
Business rules  Value Allowed: Yes 
Relationship: Table row heading 
Concept: n/a 
Duplicate field in   
other sections 
51   
Term (Variable)  Compound Number 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Enter the Sponsors unique identifier for investigational compound(s) in 
the trial.  Add or delete additional fields as needed. 
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  AN 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeatable 
other sections 
52   
Page 23 of 346 
   
Term (Variable)  Compound Number 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Enter the Sponsors unique identifier for investigational compound(s) in 
the trial.  Add or delete additional fields as needed. 
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  AN 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeatable 
other sections 
53   
Term (Variable)  Compound Name(s) 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   Compound name(s) 
Business rules  Value Allowed: n/a 
Relationship: Table row heading 
Concept: n/a 
Duplicate field in   
other sections 
54   
Page 24 of 346 
   
Term (Variable)  Nonproprietary Name 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Delete this line if a nonproprietary name has not yet been assigned. 
Omit proprietary name fields if not yet established. 
Conformance  Optional  
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   300AN 
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeatable 
other sections 
55   
Term (Variable)  Proprietary Name 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Omit proprietary name fields if not yet established. 
Conformance  Optional / Conditional 
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value    
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: Clinical trial phase 
Duplicate field in   
other sections 
56   
Page 25 of 346 
   
Term (Variable)  Additional Proprietary Name 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Omit proprietary name fields if not yet established. 
Conformance  Optional / Conditional 
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value    
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeatable 
other sections 
57   
Term (Variable)  Trial Phase 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance   
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Trial phase 
Business rules  Value Allowed: Yes 
Relationship: Table row heading 
Concept:  
Duplicate field in   
other sections 
58   
Page 26 of 346 
   
Term (Variable)  Trial Phase 
Data Type  Pick list 
Topic, Value or  D 
Header 
Definition   
User Guidance  For trials combining investigational drugs or vaccines with devices, 
classify according to the phase of drug development. 
Conformance  Required  
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Early Phase 1 
Phase 1 
Phase 1/Phase 2 
Phase 2 
Phase 2/Phase 3 
Phase 3 
Phase 4 
Other 
Business rules  Value Allowed: yes 
Relationship: n/a 
Concept: Protocol short title 
Duplicate field in   
other sections 
59   
Page 27 of 346 
   
Term (Variable)  Acronym 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Acronym 
Business rules  Value Allowed: Yes 
Relationship: Table row heading 
Concept: n/a 
Duplicate field in   
other sections 
60   
Term (Variable)  Short Title 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Short Title 
Business rules  Value Allowed: Yes 
Relationship: Table row heading 
Concept:  
Duplicate field in   
other sections 
61   
Page 28 of 346 
   
Term (Variable)  Short Title 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Explains in plain language what the trial is about and is suitable for use 
as Brief Title or Title in Plain Language in global clinical trial 
registries.  It can also be suitable for use with informed consents and 
ethics committee submissions. 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Title page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  300AN 
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: Sponsor 
Duplicate field in   
other sections 
62   
Term (Variable)  Sponsor Name and Address 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Title page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Sponsor Name and Address 
Business rules  Value Allowed: Yes 
Relationship Table row heading 
Concept: Sponsor 
Duplicate field in   
other sections 
63   
Page 29 of 346 
   
Term (Variable)  Sponsor Name 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  The legal name of the individual or pharmaceutical or medical device 
company, governmental agency, academic institution, private 
organisation, or other organisation who takes primary responsibility for 
and initiates a clinical investigation. 
User Guidance  If more than one sponsor, list the Primary Sponsor in this field.  
Conformance  Required  
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
64   
Term (Variable)  Sponsor Legal Address 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Legal address 
User Guidance  The legal address of the individual or pharmaceutical or medical device 
company, governmental agency, academic institution, private 
organisation, or other organisation who takes primary responsibility for 
and initiates a clinical investigation. 
Conformance  Required  
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
65   
Page 30 of 346 
   
Term (Variable)  Local Sponsor Name and Address 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Local Sponsor Name and Address 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
66   
Term (Variable)  Sponsor Local Name 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  In some countries, the clinical trial Sponsor may be the local affiliate 
company (or designee). In such cases, indicate in the Sponsor Local 
Name. 
User Guidance  If more than one sponsor, list the Primary Sponsor in this field.  
Conformance  Optional  
Cardinality   
Relationship content  Title page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
67   
68   
Page 31 of 346 
   
Term (Variable)  Sponsor Local Address 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Sponsor local registered address 
User Guidance  In some countries, the clinical trial Sponsor may be the local affiliate 
company (or designee).  In such cases, indicate in the Sponsor Local 
Address Field. 
Conformance  Optional  
Cardinality   
Relationship content  Title page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
69   
Term (Variable)  Manufacturer Name and Address 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Manufacturer Name and Address 
Business rules  Value Allowed: Yes 
Relationship: Table row heading 
Concept: Regulatory investigational product number 
Duplicate field in  Repeatable 
other sections 
70   
Page 32 of 346 
   
Term (Variable)  Device Manufacturer Name 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Manufacturer name and address information is required only for 
protocols that include investigational device(s) and should not be 
included for other protocols. Include the manufacturer address only if 
the manufacturer is different than the Sponsor listed above.   
Add additional fields as needed if multiple investigational devices will be 
used in the trial. Delete this line from the table if not applicable. 
Conformance  Optional  
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeatable 
other sections 
71   
Page 33 of 346 
   
Term (Variable)  Device Manufacturer Address 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Manufacturer name and address information is required only for 
protocols that include investigational device(s) and should not be 
included for other protocols. Include the manufacturer address only if 
the manufacturer is different than the Sponsor listed above.   
Add additional fields as needed if multiple investigational devices will be 
used in the trial. Delete this line from the table if not applicable. 
Conformance  Optional  
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeatable 
other sections 
72   
Page 34 of 346 
   
Term (Variable)  Regulatory Agency Identifier Number(s) 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  Include all numbers that are applicable for the trial and available at the 
time of protocol or amendment finalisation.  Delete prompts for numbers 
not available at the time of document finalisation.  Delete unused fields.  
Add fields for other if more than one is needed. 
Conformance  Required 
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Regulatory Agency Identifier Number(s): 
Business rules  Value Allowed: Yes 
Relationship: Table row heading 
Concept: Regulatory investigational product number 
Duplicate field in   
other sections 
73   
Term (Variable)  EUDAMED  
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional /  
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  EUDAMED 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: Protocol approval date 
Duplicate field in   
other sections 
74   
Page 35 of 346 
   
Term (Variable)  EUDAMED Number 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional / Conditional 
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
75   
Term (Variable)  EudraCT Number 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  EudraCT Number 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: Protocol approval date 
Duplicate field in   
other sections 
76   
Page 36 of 346 
   
Term (Variable)  EudraCT Number 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional / Conditional 
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
77   
Term (Variable)  EU Trial Number 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  EU Trial Number 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: Protocol approval date 
Duplicate field in   
other sections 
78   
Page 37 of 346 
   
Term (Variable)  EU Trial Number 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional / Conditional 
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
79   
Term (Variable)  IDE  
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Title page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  IDE 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: Protocol approval date 
Duplicate field in   
other sections 
80   
Page 38 of 346 
   
Term (Variable)  IDE Number 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional / Conditional 
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
81   
Term (Variable)  IND Number 
Data Type   
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  IND 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: Protocol approval date 
Duplicate field in   
other sections 
82   
Page 39 of 346 
   
Term (Variable)  IND Number 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional / Conditional 
Cardinality   
Relationship content  Title page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
83   
Term (Variable)  jRCT 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional / 
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  jRCT 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: Protocol approval date 
Duplicate field in   
other sections 
84   
Page 40 of 346 
   
Term (Variable)  jRCT Number 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional / Conditional 
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
85   
Term (Variable)  NCT  
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional /  
Cardinality   
Relationship content  Title page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  NTC 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: Protocol approval date 
Duplicate field in   
other sections 
86   
Page 41 of 346 
   
Term (Variable)  NCT Number 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional / Conditional 
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a  
Duplicate field in   
other sections 
87   
Term (Variable)  NMPA IND 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  NMPA IND 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: Protocol approval date 
Duplicate field in   
other sections 
88   
Page 42 of 346 
   
Term (Variable)  NMPA IND Number 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional / Conditional 
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: Protocol approval date 
Duplicate field in   
other sections 
89   
Term (Variable)  WHO  
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional /  
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  WHO 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: Protocol approval date 
Duplicate field in   
other sections 
90   
Page 43 of 346 
   
Term (Variable)  WHO Number 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional / Conditional 
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
91   
Term (Variable)  Other 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Other 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: Protocol approval date 
Duplicate field in   
other sections 
92   
Page 44 of 346 
   
Term (Variable)  Other Number 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional / Conditional 
Cardinality   
Relationship content  Title Page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeatable 
other sections 
93   
Term (Variable)  Sponsor Approval Date 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required / Required 
Cardinality   
Relationship content  Title page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Sponsor Approval Date 
Business rules  Value Allowed: Yes 
Relationship: Table row heading 
Concept: n/a 
Duplicate field in   
other sections 
94   
Page 45 of 346 
   
Term (Variable)  Approval Date 
Data Type  Date 
Topic, Value or  D 
Header 
Definition   
User Guidance  All versions should be uniquely identifiable.  Use the date format 
(dd/mmm/yyyy, for example 07/JUN/2015) to indicate the date the 
protocol (or amendment) was approved by the Sponsor. 
Conformance  Required Choice 
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  dd/mmm/yyyy  date format 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
95   
Term (Variable)  The approval date is included with the electronic signature, located 
{describe location} 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required / Choice 
Cardinality   
Relationship content  Title page  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: Sponsor representative 
Duplicate field in   
other sections 
96   
Page 46 of 346 
   
Term (Variable)  Sponsor Signatory 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Function(s) and roles authorised by the sponsor to sign the protocol and 
any substantial amendments. 
User Guidance   
Conformance  Conditional 
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Sponsor Signatory 
Business rules  Value Allowed: Yes 
Relationship: IF CHOICE, THEN approval date is included with the 
electronic signature 
Concept: n/a 
Duplicate field in   
other sections 
97   
Term (Variable)  Wet Signature image 
Data Type  Image 
Topic, Value or  D 
Header 
Definition   
User Guidance  Where allowed, an electronic/digital signature may be used for approval 
rather than a wet signature.  In such cases, replace the signature block 
with appropriate description of the electronic/digital approval and the 
location of relevant information for traceability. 
Conformance  Optional  
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
98   
Page 47 of 346 
   
Term (Variable)  Digital Signature 
Data Type  Image 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
99   
Term (Variable)  Name 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Title page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
100   
Page 48 of 346 
   
Term (Variable)  Title of Sponsor Signatory 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
101   
Term (Variable)  Sponsor Signatory Date 
Data Type  Date 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  dd/mmm/yyyy  date format 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
102   
Page 49 of 346 
   
Term (Variable)  [This protocol was approved via {describe method} as described on the 
approval page appended to the document] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Where allowed, an electronic/digital signature may be used for approval 
rather than a wet signature.  In such cases, replace the signature block 
with appropriate description of the electronic/digital approval and the 
location of relevant information for traceability. 
Conformance  Optional  
Cardinality   
Relationship content  Title Page 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  [This protocol was approved via {describe method} as described on the 
approval page appended to the document] 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
103   
Term (Variable)  {describe method} 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Where allowed, an electronic/digital signature may be used for approval 
rather than a wet signature.  In such cases, replace the signature block 
with appropriate description of the electronic/digital approval and the 
location of relevant information for traceability. 
Conformance  Optional / Conditional 
Cardinality   
Relationship content  Investigator Signature Page  
from ToC 
 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Not transferred during IND/CTA process 
Duplicate field in   
other sections 
104   
Page 50 of 346 
   
Term (Variable)  Medical Monitor Name and Contact Information 
Data Type   
Topic, Value or   
Header 
Definition   
User Guidance   
Conformance   
Cardinality   
Relationship content  Investigator Signature Page  
from ToC 
 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules   
Duplicate field in   
other sections 
105   
Term (Variable)  Medical Monitor Institution Name 
Data Type   
Topic, Value or   
Header 
Definition   
User Guidance   
Conformance   
Cardinality   
Relationship content  Investigator Signature  Page  
from ToC 
 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Not transferred during IND/CTA process 
Duplicate field in   
other sections 
106   
Page 51 of 346 
   
Term (Variable)  Medical Monitor Institution Address 
Data Type   
Topic, Value or   
Header 
Definition   
User Guidance   
Conformance   
Cardinality   
Relationship content  Investigator Signature Page  
from ToC 
 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules   
Duplicate field in   
other sections 
107   
Term (Variable)  Provided Separately/can be found {describe location}] 
Data Type   
Topic, Value or   
Header 
Definition   
User Guidance   
Conformance   
Cardinality   
Relationship content  Investigator Signature Page  
from ToC 
 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Not transferred during IND/CTA process 
Duplicate field in   
other sections 
108   
Page 52 of 346 
   
Term (Variable)  {describe location} 
Data Type   
Topic, Value or   
Header 
Definition   
User Guidance   
Conformance   
Cardinality   
Relationship content  Investigator Signature Page  
from ToC 
 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Not transferred during IND/CTA process 
Duplicate field in   
other sections 
109   
Term (Variable)  Report Serious Adverse Events within 24 hours {via E-mail/fax provided 
in the site manual. /per the options below:} 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required / Required 
Cardinality   
Relationship content  Investigator Signature Page  
from ToC 
 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Report Serious Adverse Events within 24 hours {via E-mail/fax provided 
in the site manual. /per the options below:} 
Business rules  Value Allowed: Not transferred during IND/CTA process 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
110   
Page 53 of 346 
   
Term (Variable)  Email 
Data Type   
Topic, Value or   
Header 
Definition   
User Guidance   
Conformance   
Cardinality   
Relationship content  Investigator Signature Page  
from ToC 
 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Email: 
Business rules  Not transferred during IND/CTA process 
Duplicate field in   
other sections 
111   
Term (Variable)  {Rapid Alert email address} 
Data Type   
Topic, Value or   
Header 
Definition   
User Guidance   
Conformance   
Cardinality   
Relationship content  Investigator Signature Page  
from ToC 
 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Not transferred during IND/CTA process 
Duplicate field in   
other sections 
112   
Page 54 of 346 
   
Term (Variable)  Fax 
Data Type   
Topic, Value or   
Header 
Definition   
User Guidance   
Conformance   
Cardinality   
Relationship content  Investigator Signature Page  
from ToC 
 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Not transferred during IND/CTA process 
Duplicate field in   
other sections 
113   
Term (Variable)  {Rapid Alert Fax Number" 
Data Type   
Topic, Value or   
Header 
Definition   
User Guidance   
Conformance   
Cardinality   
Relationship content  Investigator Signature Page  
from ToC 
 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Not transferred during IND/CTA process 
 
 
Duplicate field in   
other sections 
114   
115   
Page 55 of 346 
   
Term (Variable)  Amendment Details 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  Delete this entire section if this is the original protocol. 
Conformance  Required / Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Amendment Details 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Not required for original 
other sections 
116   
Page 56 of 346 
   
Term (Variable)  History of Amendment 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance  Do not include the current amendment in the table below, as final 
approval dates are often difficult to predict during document preparation.  
Previous amendments, including regional amendments, should appear in 
reverse chronological order with the most recent at the top (for 
example, Amendment 3, 2, 1).  Delete lines not needed, add lines as 
needed.   
 
Some regulatory agencies find the approximate number or percent of 
enrollment at the time of each amendment to be helpful, and the 
information can be repurposed in final trial reports; however, it is 
neither a protocol requirement of any agency nor expected universally.  
If including the column with enrollment numbers, list approximate global 
enrollment total or percentage at the time of the amendment and select 
globally.  For local amendments, list the approximate local enrollment 
total or percentage at the time of the amendment and select locally. 
Conformance  Required  
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  History of Amendment 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
117   
Page 57 of 346 
   
Term (Variable)  {#/A total of #} prior {global} amendments have occurred, as shown in 
the table below: 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  Do not include the current amendment in the table below, as final 
approval dates are often difficult to predict during document preparation.  
Previous amendments should appear in reverse chronological order with 
the most recent at the top (for example, Amendment 3, 2, 1).  Delete 
lines not needed, add lines as needed.  Inclusion of regional-, country-, 
and site-specific amendments in the table is optional.  If included, 
ensure that the scope is clearly distinguishable from global amendments. 
If including the column with enrollment numbers, follow the instructions 
below. 
  For global amendments, list approximate global enrollment total 
or percentage at the time of the amendment and select globally.   
  For local amendments, list the approximate local enrollment total 
or percentage at the time of the amendment and select locally. 
Conformance  Required  
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  {#/A total of #} prior {global} amendments have occurred, as shown in 
the table below: 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
118   
Page 58 of 346 
   
Term (Variable)  prior amendments have occurred as shown in table below: 
Data Type  Number 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required / Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
119   
Term (Variable)  Document 
Data Type  Table col head 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required / Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Document 
Business rules  Value Allowed: Yes 
Relationship: row title 
Concept: Amendment Date 
Duplicate field in   
other sections 
120   
Page 59 of 346 
   
Term (Variable)  Sponsor Approval Date (dd/mm/yyyy) 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Sponsor Approval Date (dd/mm/yyyy) 
Business rules  Value Allowed: Yes 
Relationship: Row title 
Concept: n/a 
Duplicate field in   
other sections 
121   
Term (Variable)  Approximate {(#/%)} enrolled 
Data Type  Table col head 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Approximate {(#/%)} enrolled 
Business rules  Value Allowed: Yes 
Relationship: Row title 
Concept: n/a 
Duplicate field in   
other sections 
122   
Page 60 of 346 
   
Term (Variable)  Original or Amendment X 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required / Repeatable 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Original or Amendment 
Business rules  Value Allowed: Yes 
Relationship: Row title 
Concept: n/a 
Duplicate field in  Repeat for each amendment 
other sections 
123   
Term (Variable)  X 
Data Type  integer 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Conditional / Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: Rows content 
Concept: n/a 
Duplicate field in  Repeat for each amendment 
other sections 
124   
Page 61 of 346 
   
Term (Variable)  Amendment X Date 
Data Type  date dd/mmm/yyyy 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Conditional / Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: Rows content 
Concept: n/a 
Duplicate field in  Repeat for each amendment 
other sections 
125   
Term (Variable)  {(#/%)} {globally/locally}} 
Data Type  integer 
Topic, Value or  D 
Header 
Definition  Estimated # of participants enrolled as a percentage of the expected 
total. 
User Guidance  Good estimates are adequate, as precise enrolment figures will likely be 
changing while an amendment is being prepared. 
Conformance  Conditional / Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  " " % 
Business rules  Value Allowed: Yes 
Relationship: Rows content 
Concept: n/a 
Duplicate field in  Repeat for each amendment 
other sections 
126   
Page 62 of 346 
   
Term (Variable)  {(#/%)} {globally/locally}} 
Data Type  Pick list 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Conditional / Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Global 
Local 
Business rules  Value Allowed: Yes 
Relationship: Rows content 
Concept: n/a 
Duplicate field in  Repeat for each amendment 
other sections 
127   
Term (Variable)  Current Amendment 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Current Amendment 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
128   
Page 63 of 346 
   
Term (Variable)  The table below provides an overview of the current amendment 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  The table below provides an overview of the current amendment 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Not included in original 
other sections 
129   
Term (Variable)  Amendment Number 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Amendment Number 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
130   
Page 64 of 346 
   
Term (Variable)  Amendment Number 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Row 23 in BoR 
other sections 
131   
Term (Variable)  Approximate {(#/%)} enrolled 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Approximate {(#/%)} enrolled 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
132   
Page 65 of 346 
   
Term (Variable)  Number or % 
Data Type  Integer 
Topic, Value or  D 
Header 
Definition  Estimated # of participants enrolled as a percentage of the expected 
total. 
User Guidance  Good estimates are adequate, as precise enrolment figures will likely be 
changing while an amendment is being prepared. 
Conformance  Required  
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
 
 
Duplicate field in  Row 101 of BoR 
other sections 
133   
Term (Variable)  Reason(s) for Amendment 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Reason(s) for Amendment: 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
134   
Page 66 of 346 
   
Term (Variable)  Primary 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Primary: 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
135   
Page 67 of 346 
   
Term (Variable)  Primary Reason for Amendment 
Data Type  Pick list  
Topic, Value or  D 
Header 
Definition   
User Guidance  Choose from the available categories as the primary reason for the 
amendment.  Select the closest match among the choices.  Changes to 
key measures or endpoints should be listed as a change of 
strategy/objective. If none apply, choose other and provide a 
description.  Categories are derived from Getz, et al., DIA TIRS, 2016 
The Impact of Protocol Amendments on Clinical Trial Performance and 
Cost.   
Conformance  Required  
Cardinality  Amendment Details 
Relationship content   
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value    Regulatory agency request to amend 
  New regulatory guidance 
  IRB/IEC feedback 
  New safety information available 
  Manufacturing change 
  Adaptive clinical trial IMP addition 
  Change in strategy  
  Change in standard of care 
  New data available (other than safety data) 
  Investigator/site feedback 
  Recruitment difficulty 
  Inconsistency and/or error in the protocol 
  Protocol design error 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Multiple accepted 
other sections 
136   
Page 68 of 346 
   
Term (Variable)  Other 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Other: 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a  
Duplicate field in   
other sections 
137   
Term (Variable)  Other description 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a  
Duplicate field in   
other sections 
138   
Page 69 of 346 
   
Term (Variable)  Primary Reason for Amendment 
Data Type  Pick List 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required / Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value    Regulatory agency request to amend 
  New regulatory guidance 
  IRB/IEC feedback 
  New safety information available 
  Manufacturing change 
  Adaptive clinical trial IMP addition 
  Change in strategy  
  Change in standard of care 
  New data available (other than safety data) 
  Investigator/site feedback 
  Recruitment difficulty 
  Inconsistency and/or error in the protocol 
  Protocol design error 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Multiple accepted 
other sections 
139   
Page 70 of 346 
   
Term (Variable)  Other 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Conditional / Optional 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Other: 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a  
Duplicate field in   
other sections 
140   
Term (Variable)  Other description 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Conditional / Optional 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a  
Duplicate field in   
other sections 
141   
Page 71 of 346 
   
Term (Variable)  Summary of Amendment 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Conditional / Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Summary of Amendment 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
142   
Term (Variable)  Summary of Amendment 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Conditional / Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
143   
Page 72 of 346 
   
Term (Variable)  Question 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Conditional / Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Is this amendment likely to have a substantial impact on  
  safety or rights of the subjects, or 
  on the reliability and robustness of the data generated in the 
clinical trial? 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
144   
Term (Variable)  Yes/No 
Data Type  Pick list 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Conditional / Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Yes 
No 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
145   
Page 73 of 346 
   
Term (Variable)  Summary of Changes in Current Amendment 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section heading 
User Guidance  Follow the steps below to prepare the summary of changes. 
  If a Summary of Changes already exists from a prior amendment, 
move it to Section 12.5, History of Previous Amendments, and populate 
a clean summary table for the present amendment.   
  List the changes that apply to the current amendment.  Provide a 
brief description of the change(s) and a brief scientific rationale for 
specific changes (for example, change to individual inclusion/exclusion 
criteria).   
Tabular presentation is common but not required.  The page can be 
changed to landscape orientation if necessary. 
Conformance  Conditional / Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Summary of Changes in Current Amendment 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: Protocol short title 
Duplicate field in   
other sections 
146   
Page 74 of 346 
   
Term (Variable)  Section # and Name 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Section # and Name 
Business rules  Value Allowed: Yes 
Relationship: Rows content 
Concept: Trial purpose summary 
Duplicate field in  Repeat until complete 
other sections 
147   
Term (Variable)  Location of Change 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: Rows content 
Concept: Trial purpose summary 
Duplicate field in  Repeat until complete 
other sections 
148   
Page 75 of 346 
   
Term (Variable)  Description of Change 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Description of Change 
Business rules  Value Allowed: Yes 
Relationship: Rows content 
Concept: Primary Objective 
Duplicate field in  Repeat until complete 
other sections 
149   
Term (Variable)  Description of Change 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: Rows content 
Concept: Primary endpoint 
Duplicate field in  Repeat until complete 
other sections 
150   
Page 76 of 346 
   
Term (Variable)  Brief Rationale for Change 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Brief Rationale for Change 
Business rules  Value Allowed: Yes 
Relationship: Rows content 
Concept: Primary endpoint 
Duplicate field in  Repeat until complete 
other sections 
151   
Term (Variable)  Brief Rationale for Change 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Amendment Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: Rows content 
Concept: n/a 
Duplicate field in  Repeat until complete 
other sections 
152   
Page 77 of 346 
   
Term (Variable)  Table of Contents 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Table of Contents 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Table of Contents 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
153   
Page 78 of 346 
   
Term (Variable)  Table of Contents 
Data Type   
Topic, Value or   
Header 
Definition   
User Guidance   
Conformance  Generated / Generated 
Cardinality   
Relationship content   
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
154  1.  Protocol Summary 
Term (Variable)  Protocol Summary 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  No text is intended here (header only) 
Conformance  Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  1. Protocol Summary 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
155   
Page 79 of 346 
   
156  1.1  Protocol Synopsis 
Term (Variable)  1.1 Protocol Synopsis 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Header 
User Guidance  The protocol synopsis is a short summary of the key points of the trial. 
No text is intended here (header only). 
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  1.1 Protocol Synopsis 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: Secondary endpoint(s) 
Duplicate field in   
other sections 
157   
Term (Variable)  Primary Objective 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Primary Objective 
Business rules  Value Allowed: Yes 
Relationship: Table header 
Concept: n/a 
Duplicate field in  Section 3.1 replicated for primary/secondary 
other sections 
158   
Page 80 of 346 
   
Term (Variable)  Objective X 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Define the primary objective(s) and the rationale for the objective(s). 
Where applicable, provide information about the relevance of the 
objective. For multi-arm studies, ensure that each objective clarifies the 
way in which all of the intervention groups will be compared (e.g., A 
versus B, A versus C). 
Conformance  Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: Relate endpoint 
Concept: n/a 
Duplicate field in  Repeat as needed 
other sections 
 
159   
Term (Variable)  Primary Endpoint 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Primary Endpoint 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
160   
Page 81 of 346 
   
Term (Variable)  Endpoint X 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Define each primary endpoint(s) and the rationale for each endpoint(s). 
The endpoint is the variable of interest that will be obtained for each 
participant. The endpoint should be a clear, unambiguous, quantitative 
measure directly related to the corresponding objective. 
It may be pertinent to list the additional time points at which the 
endpoint/outcome will be measured if it is possible to be measured more 
than once during the trial. 
Conformance  Conditional / Conditional 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: Relate to objective 
Concept: n/a 
Duplicate field in  Must be at least one endpoint per objective 
other sections  May be more than one endpoint per objective 
Repeat as needed 
 
161   
Page 82 of 346 
   
Term (Variable)  Secondary Objective 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required / Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Secondary Objective 
Business rules  Value Allowed: Yes 
Relationship: Table header 
Concept: n/a 
Duplicate field in  Section 3.1 replicated for primary/secondary 
other sections 
162   
Term (Variable)  Objective X 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Define the secondary objective(s) and the rationale for the objective(s). 
Where applicable, provide information about the relevance of the 
objective. 
Conformance  Required / Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: Relate endpoint 
Concept: n/a 
Duplicate field in  Repeat as needed 
other sections 
163   
Page 83 of 346 
   
Term (Variable)  Secondary Endpoint 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Secondary Endpoint 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
164   
Term (Variable)  Endpoint X 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Define each secondary endpoint(s) and the rationale for each 
endpoint(s).  
Conformance  Conditional / Conditional 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: Relate to object 
Concept: n/a 
Duplicate field in  Must be at least one endpoint per objective 
other sections 
May be more than one endpoint per objective 
repeat as needed 
165   
Page 84 of 346 
   
Term (Variable)  Overall Design 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Protocol Summary  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Overall Design 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
166   
Term (Variable)  Several key aspects of the trial design are summarised below 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Several key aspects of the trial design are summarised below 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
167   
Page 85 of 346 
   
Term (Variable)  Intervention Model 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Intervention Model 
Business rules  Value Allowed: Yes 
Relationship: Table Cell title 
Concept: n/a 
Duplicate field in   
other sections 
168   
Term (Variable)  Intervention Model 
Data Type  Pick List 
Topic, Value or  D 
Header 
Definition   
User Guidance  Intervention model (for example, single group, parallel group, cross-
over, factorial, sequential, other) 
Conformance  Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Single group, parallel group, cross-over, factorial, sequential, other 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
169   
Page 86 of 346 
   
Term (Variable)  Population Type 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Population Type 
Business rules  Value Allowed: Yes 
Relationship: Table Cell title 
Concept: n/a 
Duplicate field in   
other sections 
170   
Term (Variable)  Population Type 
Data Type  Pick List 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  healthy volunteers, adult patients, paediatric patients, other 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
171   
Page 87 of 346 
   
Term (Variable)  Control 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Control 
Business rules  Value Allowed: Yes 
Relationship: Table cell title 
Concept: n/a 
Duplicate field in   
other sections 
172   
Term (Variable)  Control 
Data Type  Pick List 
Topic, Value or  D 
Header 
Definition   
User Guidance  Control method (for example, placebo, active comparator, low dose, 
historical, standard of care, sham procedure, or none [uncontrolled]) 
Conformance  Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  placebo, active comparator, low dose, historical, standard of care, sham 
procedure, or none [uncontrolled] 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
173   
Page 88 of 346 
   
Term (Variable)  Population Diagnosis or Condition 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Population Diagnosis or Condition 
Business rules  Value Allowed: Yes 
Relationship: Table cell title 
Concept: n/a 
Duplicate field in   
other sections 
174   
Term (Variable)  Population Diagnosis or Condition 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Control method (for example, placebo, active comparator, low dose, 
historical, standard of care, sham procedure, or none [uncontrolled]) 
Conformance  Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  CT: acute lung injury, or a specific biomarker profile); indicate N/A  
Healthy for studies in healthy volunteers 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
175   
176   
Page 89 of 346 
   
Term (Variable)  Active Comparator 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Active Comparator 
Business rules  Value Allowed: Yes 
Relationship: Table Cell title 
Concept: n/a 
Duplicate field in   
other sections 
177   
Term (Variable)  Active Comparator 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Active comparator, if applicable; indicate N/A if not applicable. 
Conformance  Conditional/ Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  If applicable; indicate N/A if not applicable 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
178   
Page 90 of 346 
   
Term (Variable)  Population Age 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  Population age range (for example 0-3 mos, 18-80 years old).  List N/A 
if a maximum or minimum age limit does not apply.  For trials in which 
multiple age ranges may be eligible (for example, a younger cohort and 
an older cohort), indicate the minimum and maximum ages for the trial 
overall, with an additional comment for any excluded age ranges. 
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Population Age 
Business rules  Value Allowed: Yes 
Relationship: Table cell title 
Concept: n/a 
Duplicate field in   
other sections 
179   
Term (Variable)  Minimum 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Minimum 
Business rules  Value Allowed: Yes 
Relationship: Table cell entry 
Concept: n/a 
Duplicate field in   
other sections 
180   
Page 91 of 346 
   
Term (Variable)  Minimum age 
Data Type  Integer 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
181   
Term (Variable)  Maximum 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Maximum 
Business rules  Value Allowed: Yes 
Relationship: Table Cell entry 
Concept: n/a 
Duplicate field in   
other sections 
182   
Page 92 of 346 
   
Term (Variable)  Maximum age 
Data Type  Integer 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
183   
Term (Variable)  Age units 
Data Type  Pick List 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Weeks, months, years 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
184   
Page 93 of 346 
   
Term (Variable)  Trial Intervention Assignment Method 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Trial Intervention Assignment Method 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
185   
Term (Variable)  Trial Intervention Assignment Method 
Data Type  Pick List 
Topic, Value or  D 
Header 
Definition   
User Guidance  Trial intervention assignment method (for example, randomisation, 
stratification, or both). Do NOT state block size. If assignment to 
intervention is by randomisation, describe when randomisation occurs 
relative to screening. 
Conformance  Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Randomisation, stratification, or both randomisation and stratification 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
186   
Page 94 of 346 
   
Term (Variable)  Randomisation time 
Data Type   
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Conditional  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Relative to screening 
Business rules  Value Allowed: Yes 
Relationship: Randomisation 
Concept: n/a 
Duplicate field in   
other sections 
187   
Term (Variable)  Site Distribution 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Site Distribution 
Business rules  Value Allowed: Yes 
Relationship: N/A 
Concept: n/a 
 
 
Duplicate field in   
other sections 
188   
189   
Page 95 of 346 
   
Term (Variable)  Geographic scope 
Data Type  Pick List 
Topic, Value or  D 
Header 
Definition  Geographic scope of trial 
User Guidance  Geographic scope of trial (select from: single-centre, multi-centre, or 
multi-centre and multi-national).  If none of these applies, indicate other 
and describe. 
Conformance  Required / Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Examples: single-center, multi-center, or multi-center, multi-national 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
190   
Term (Variable)  Geographic scope other 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Conditional / Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  ISO Country Code List 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
191   
Page 96 of 346 
   
Term (Variable)  Number of Arms 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Number of Arms 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
192   
Term (Variable)  Number of Arms 
Data Type  integer 
Topic, Value or  D 
Header 
Definition   
User Guidance  Enter the numeric value for the number of arms in the trial. For trials 
with a different number of arms in different periods, populate this field 
based on the period with the greatest number of arms. 
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Greatest number of arms 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
193   
Page 97 of 346 
   
Term (Variable)  Blinding 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Blinding 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
194   
Term (Variable)  The following roles indicated below will not be made aware of the 
treatment group assignment during the trial 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  The following roles indicated below will not be made aware of the 
treatment group assignment during the trial 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
195   
Page 98 of 346 
   
Term (Variable)  Blinding roles 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  For trial designs in which these details may differ in one or more trial 
periods, answer according to the portion of the trial in which the 
greatest blinding occurs. More details can be provided in the main body 
of the protocol.  Note that this list does not include Sponsor staff or their 
designees who are routinely unmasked to complete ongoing safety 
oversight and surveillance reporting. 
Conformance  Required / Conditional 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Participant, Care Provider, Investigator, Outcomes Assessor, Not 
applicable, No Blinding 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
196   
Term (Variable)  Number of participants 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
197   
Page 99 of 346 
   
Term (Variable)  Number  
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  State the expected number of participants to be assigned to trial 
intervention.  Indicate whether the number provided is the target or 
maximum number of individuals to be enrolled. 
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Number 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
198   
Term (Variable)  [randomly assigned to trial intervention/enrolled] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance    
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Randomly assigned to Trial intervention/ enrolled 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
199   
Page 100 of 346 
   
Term (Variable)  {x} 
Data Type  Integer 
Topic, Value or  D 
Header 
Definition   
User Guidance    
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
200   
Term (Variable)  [Target/Maximum] 
Data Type  Integer 
Topic, Value or  D 
Header 
Definition   
User Guidance    
Conformance  Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Target/Maximum 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
201   
Page 101 of 346 
   
Term (Variable)  Arms and Duration 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  Select the text that applies to the trial.  Note that total duration of 
participation should include any washout and any follow-up periods in 
which the participant is not receiving trial intervention.  Where the total 
durations can be provided, indicate whether the duration is approximate, 
and delete terms that are not applicable (for example, for a trial of only 
a few days, delete the years and months terms).  When duration cannot 
be approximated, provide a short explanation (for example, event-
driven or adaptive design). 
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Arms and Duration 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
202   
Term (Variable)  Total duration of trial intervention for each participant: 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance    
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Total duration of trial intervention for each participant: 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
203   
Page 102 of 346 
   
Term (Variable)  Approximately 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Choice 1 / Required 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Approximately 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
204   
Term (Variable)  X 
Data Type  Integer 
Topic, Value or  D 
Header 
Definition   
User Guidance    
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
205   
Page 103 of 346 
   
Term (Variable)  Year(s)/[x] Month(s)/[x] Day(s) 
Data Type  Pick List 
Topic, Value or  D 
Header 
Definition   
User Guidance    
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
206   
Term (Variable)  Duration will vary 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance    
Conformance  Choice 2  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Duration will vary 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
207   
Page 104 of 346 
   
Term (Variable)  Reason duration of trial participation will vary 
Data Type  Pick List  
Topic, Value or  D 
Header 
Definition   
User Guidance    
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Event-driven or adaptive design 
Business rules  Value Allowed: Yes 
Relationship: Complete 
Concept: n/a 
Duplicate field in   
other sections 
208   
Term (Variable)  Arms and Duration Description 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance    
Conformance  Optional 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Arms and Duration Description 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
209   
Page 105 of 346 
   
Term (Variable)  Total duration of trial participation for each participant with sequence 
and duration of trial periods (for example, screening, run-in, fixed 
dose/titration, follow-up/washout periods 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance    
Conformance  Optional  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
210   
Term (Variable)  Dose regimens in each trial period and stage (if applicable) including 
frequency (for example, twice daily) and route of administration and 
criteria for individualised dosing (for example, participant weight or 
plasma concentrations), if applicable. 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance    
Conformance  Optional  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
211   
Page 106 of 346 
   
Term (Variable)  Rules/procedures for any dose changes/adjustments including flexible 
dosing; dose reductions, dose interruptions, or tapering; 
discontinuation; and any circumstances for resuming trial intervention, 
as applicable 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance    
Conformance  Optional  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
212   
Page 107 of 346 
   
Term (Variable)  Committee 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  Indicate whether any committee(s) will be reviewing data while the trial 
is ongoing, and the type of committee.  Common examples include Data 
Monitoring Committee, Dose Escalation Committee, or Endpoint 
Adjudication Committee; describe others, if applicable.   List 
independent committees in the space indicated.  Other committees may 
be included at the Sponsors discretion in the separate space provided.  
Committees listed here should be fully described in Section 10.3, 
Committees Structure. 
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Committee 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
213   
Page 108 of 346 
   
Term (Variable)  Committee Name 
Data Type  Pick List 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Data Monitoring Committee, Dose Escalation Committee, or Endpoint Adjudication 
Committee, other none 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
214   
Term (Variable)  sponsor committee 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeat as needed 
other sections 
215   
Page 109 of 346 
   
Term (Variable)  Independent Committees: 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Independent Committees: 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
216   
Term (Variable)  Independent Committee Name 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  n/a or text value 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeat as needed 
other sections 
217   
Page 110 of 346 
   
Term (Variable)  Independent Other committee 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeat as needed 
other sections 
218   
Term (Variable)  other Committees: 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  other Committees: 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
219   
Page 111 of 346 
   
Term (Variable)  Other Committee Name 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a  
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
220   
Page 112 of 346 
   
221  1.2  Trial Schema 
Term (Variable)  Trial Schema 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance  The purpose of this section is to provide a visual depiction of the trial 
design, orienting users of the protocol to the key features of the trial 
design.  The schema depicts the trial arms, the flow of individual 
participants through the progression of trial period(s)/epochs (such as 
screening, washout/run-in, intervention, and key milestones [for 
example, randomisation, cross-over, end of treatment]).  For complex 
trials, additional schemas may be added to describe activities or trial 
periods in greater detail. 
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Trial Schema 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
222   
Page 113 of 346 
   
Term (Variable)  Trial Schema 
Data Type  Image 
Topic, Value or  D 
Header 
Definition  Visual depiction of the trial design, orienting users of the protocol to the 
key features of the trial design. The schema depicts the flow of 
individual participants through the progression of trialtrial 
period(s)/epochs (such as screening, washout/run-in, intervention, and 
key milestones (for example, randomisation, crossover, end of 
treatment). 
User Guidance  Key visits may also be included to aid understanding and accurate 
execution of the trial and should correspond to the details presented in 
the Schedule of Activities.  Reviewers will appreciate information 
regarding the number of subjects per treatment group, number of 
treatment groups, how participants are randomised to treatment groups, 
and duration of trial.  Usually, trial schemas are presented with time 
progressing from left to right.  The page can be changed to landscape 
orientation, if necessary. 
The schema should fit onto a single page and reflect the entire duration 
of the trial.  For complex trials, additional schemas may be added to 
describe activities or trial periods in greater detail. 
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
223   
Page 114 of 346 
   
Term (Variable)  Trial Schema discussion 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
224   
Page 115 of 346 
   
225  1.3  Schedule of Activities 
Term (Variable)  Schedule of Activities 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance  The schedule of activities must capture the procedures that will be 
accomplished at each trial visit, and all contact with trial participants, for 
example, telephone contacts. This includes any tests that are used for 
eligibility, participant randomisation or stratification, or decisions on trial 
intervention discontinuation. Allowable windows should be stated for all 
visits. 
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Schedule of Activities 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
226   
Page 116 of 346 
   
Term (Variable)  Schedule of Activities 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Protocol Summary 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
227  2.  Introduction 
Term (Variable)  Introduction 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Introduction 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Introduction 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
228   
Page 117 of 346 
   
229  2.1  Purpose of Trial 
Term (Variable)  Purpose of Trial 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Introduction 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Purpose of Trial 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
230   
Page 118 of 346 
   
Term (Variable)  Purpose of Trial 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Clear explanation of the research question/hypothesis and the 
justification of the trial i.e. why the question is worth asking and, 
through consultation with public and patient groups, why answering this 
question is worthwhile to patients. 
User Guidance  Explain why the trial is needed, why the research questions being asked 
are important and, where applicable, why closely related questions are 
not being covered. Do not restate the IB. 
Conformance  Required  
Cardinality   
Relationship content  Introduction  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
231   
Page 119 of 346 
   
232  2.2  Summary of Benefits and Risks 
Term (Variable)  Summary of Benefits and Risks 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Introduction  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Summary of Benefits and Risks 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
233   
Term (Variable)  Benefit Summary 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Introduction 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Benefit Summary 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
234   
Page 120 of 346 
   
Term (Variable)  Benefit Summary 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  The benefit summary should be written from the perspective of an 
individual participant, and should describe any physical, psychological, 
social, legal, or any other potential benefits to individual participants as 
a result of participating in the trial, addressing immediate potential 
benefits and/or long-range potential benefits.  Clearly state if no benefits 
to an individual participant can be anticipated, or if potential benefits are 
unknown.  For early clinical studies such as Phase 1, benefits for an 
individual participant (other than those of altruism) are expected to be 
minimal.  
Benefits to society in general may also be included but should be 
discussed separately. 
Conformance  Required  
Cardinality   
Relationship content  Introduction 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
235   
Page 121 of 346 
   
Term (Variable)  Risk Summary and Mitigation Strategy 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Introduction  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Risk Summary and Mitigation Strategy 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
236   
Term (Variable)  Trial Specific Discussion of intervention Risks and Mitigation 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Trial Intervention  Discuss risks related to trial-specific treatments and 
interventions. For the protocol, focus discussion only on the relevant key 
risks for THIS trial. Provide a brief description of strategies to mitigate 
identified risks or provide a cross-reference to the relevant protocol 
section. 
Conformance  Required  
Cardinality   
Relationship content  Introduction  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
237   
Page 122 of 346 
   
Term (Variable)  Trial Specific discussion of Procedure (s) Risks and Mitigation 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Trial Procedures  Consider risks associated with the trial design and 
procedures specific to THIS trial (for example, biopsies) or design (for 
example, placebo arm), and any measures to control the risks. Provide a 
brief description of strategies to mitigate identified risks or provide a 
cross-reference to the relevant protocol section. This is not intended to 
be an exhaustive list of all possible risks associated with trial procedures 
but should focus on the unique risks inherent in the design or less 
common or high-risk procedures. As above, provide a brief description of 
strategies to mitigate identified risks or provide a cross-reference to the 
relevant protocol section. 
Conformance  Required  
Cardinality   
Relationship content  Introduction  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
238   
Page 123 of 346 
   
Term (Variable)  Trial specific Discussion of other Risks and Mitigations 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Other  Consider risks associated with other items (for example, 
comparators, challenge agents, imaging agents, medical devices).  
Insert a line for each, as needed. 
Conformance  Required  
Cardinality   
Relationship content  Introduction  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
239   
Term (Variable)  Overall Benefit: Risk Conclusion 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Introduction  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Overall Benefit: Risk Conclusion 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
240   
Page 124 of 346 
   
Term (Variable)  Overall Benefit: Risk Conclusion 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Succinct, concluding statement on the perceived balance between risks 
that have been identified from cumulative safety data, protocol 
procedures and anticipated efficacy/benefits within the context of the 
proposed trial. 
User Guidance 
Risks need to be weighed against the benefits for the individual 
participant.  
Clinical trials should generally pose only minimal risks to incapacitated 
subjects, minors, pregnant or breastfeeding women, and clinical trials 
conducted in emergency situations.  Refer to local guidelines for specific 
requirements or benefit/risk thresholds in these populations and ensure 
that these are addressed here, if applicable.  
Outcomes of discussions with regulatory authorities as related to 
benefit/risk and reporting may be summarised here if it provides useful 
insights for the investigator. 
Conformance  Required  
Cardinality   
Relationship content  Introduction  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
241   
Page 125 of 346 
   
242  3.  Trial Objectives, Endpoints and Estimands 
Term (Variable)  Trial Objectives, Endpoints, and Estimands 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance  In this section, precisely define each clinical question of interest by 
stating each trial objective and specifying the endpoint(s) and 
estimand(s) that correspond to each trial objective. Ensure alignment 
with every other section of the protocol. 
Include additional level 2 headers under Section 3 Trial Objectives, 
Endpoints, and Estimands as needed. 
Conformance  Required  
Cardinality   
Relationship content  Trial Objectives, Endpoints, and Estimands 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Trial Objectives, Endpoints, and Estimands 
Business rules  Value Allowed: Yes 
Relationship: Master for Summary of Changes in Current Amendment 
Concept: n/a 
Duplicate field in   
other sections 
243   
Page 126 of 346 
   
244  3.1  {Primary/Secondary/Exploratory} Objective + Associated 
245  Endpoint {and Estimand} 
Term (Variable)  {Primary/Secondary/Exploratory} Objective + Associated Endpoint {and 
Estimand} 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required / Repeated 
Cardinality   
Relationship content  Trial Objectives, Endpoints, and Estimands  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  3.X  {Primary/Secondary/Exploratory} Objective + Associated 
Endpoint {and Estimand} 
Business rules  Value Allowed: Yes 
Relationship: Repeats for Primary, Secondary, Exploratory 
Concept: n/a 
Duplicate field in  Repeated and numbered for each objective-endpoint(s) combination 
other sections 
246   
Term (Variable)  {Primary/Secondary/Exploratory} Objective 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required / Repeated 
Cardinality   
Relationship content  Trial Objectives, Endpoints, and Estimands  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  {Primary/Secondary/Exploratory} Objective 
Business rules  Value Allowed: Yes 
Relationship: "Table Headers 
Repeats for primary, Secondary, Exploratory" 
Concept: n/a 
Duplicate field in  Repeated and numbered for each objective-endpoint(s) Combination 
other sections 
247   
Page 127 of 346 
   
Term (Variable)  {Primary/Secondary/Exploratory} Endpoint 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required / Repeated 
Cardinality   
Relationship content  Trial Objectives, Endpoints, and Estimands  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  {Primary/Secondary/Exploratory} Endpoint 
Business rules  Value Allowed: Yes 
Relationship: Table Headers 
Repeats for primary, Secondary, Exploratory 
Concept: n/a 
Duplicate field in  Repeated and numbered for each objective-endpoint(s) Combination 
other sections 
248   
Term (Variable)  [Objective] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required / one per number 
Cardinality   
Relationship content  Trial Objectives, Endpoints, and Estimands  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: "Table Entry one per number 
Repeats for additional" 
Concept: n/a 
Duplicate field in  Multiple relates to objective 
other sections 
Repeated and numbered for each objective-endpoint(s) combination 
249   
Page 128 of 346 
   
Term (Variable)  [Endpoint] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required / Repeated 
Cardinality   
Relationship content  Trial Objectives, Endpoints, and Estimands 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: Table entry relates to objective multiple for objective 
Repeats as aligned with objective 
Repeats 
Concept: n/a 
Duplicate field in  One per number area 
other sections 
Repeated and numbered for each objective-endpoint(s) combination 
250   
Term (Variable)  {Primary/Secondary/Exploratory} Estimand 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required / Repeated 
Cardinality   
Relationship content  Trial Objectives, Endpoints, and Estimands  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  {Primary/Secondary/Exploratory} Estimand 
Business rules  Value Allowed: Yes 
Relationship: Repeat for 
Concept: n/a 
Duplicate field in  Repeated and numbered for each objective-endpoint(s) combination 
other sections 
251   
Page 129 of 346 
   
Term (Variable)  [Estimand Description] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Describe the attributes that construct the estimand: the treatment 
condition of interest, the population of patients targeted by the clinical 
question of interest, other intercurrent events (if applicable), a 
population level summary, and the endpoint (or variable) specified in the 
table above. 
Conformance  Required / Repeat for 
Cardinality   
Relationship content  Trial Objectives, Endpoints, and Estimands  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: Repeat for 
Concept: n/a 
Duplicate field in  Repeated and numbered for each objective-endpoint(s) Combination 
other sections 
252   
Page 130 of 346 
   
253  4.  Trial Design 
Term (Variable)  Trial Design 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance  In this section, describe the trial design with specific mention, as 
applicable, of the components of an adequate and well-controlled trial. 
The description of the trial design should be concise and consistent 
across Section 1.1, Protocol Synopsis and Section 1.2, Trial Schema. 
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Trial Design 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
254   
Page 131 of 346 
   
255  4.1  Description of Trial Design 
Term (Variable)  Description of Trial Design 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  heading 
User Guidance  Describe the trial intervention model (for example, single group, parallel 
group, cross-over, factorial, sequential), the expected number of 
participants, and the control method (for example, placebo, active 
comparator, low dose, historical, standard of care, sham procedure, or 
none [uncontrolled]).  
If applicable, indicate the type of trial (for example, superiority, non-
inferiority, dose escalation, or equivalence).  
If the trial will have an adaptive or novel design (for example, the trial 
will be conducted under a master protocol), provide a summary of these 
design aspects. 
Conformance  Required / 
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Description of Trial Design 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
256   
Page 132 of 346 
   
Term (Variable)  Expected Number of Participants 
Data Type  Number 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
257   
Term (Variable)  Control Mechanism 
Data Type  List 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Placebo, active comparator, low dose, historical, standard of care, sham 
procedure, or none [uncontrolled] 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
258   
Page 133 of 346 
   
Term (Variable)  Type of Trial 
Data Type  List 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Superiority, non-inferiority, dose escalation, or equivalence 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
259   
Term (Variable)  Adaptive Trial 
Data Type  List 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Boolean (Yes/No) 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
260   
Page 134 of 346 
   
Term (Variable)  Novel Design 
Data Type  List 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Boolean (Yes/No) 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
261   
Term (Variable)  Under Master 
Data Type  List 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Boolean (Yes/No) 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
262   
Page 135 of 346 
   
Term (Variable)  [Description of Intervention Model] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Describe the trial duration with reference to Section 1.2, Trial Schema. 
Explain what the overall trial duration for an individual participant is 
anticipated to be and why, including the sequence and duration of trial 
periods (for example, screening, run-in, randomisation, treatment [fixed 
dose/titration], follow-up/washout periods).  Where applicable, include 
discussion of sentinel dosing (or lack thereof), dose escalation, and 
cohort expansion.  If dose modification decisions are dependent upon 
review by a committee, include details in Section 10.3, Committees 
Structure. 
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
263   
Page 136 of 346 
   
Term (Variable)  [Description of Trial Duration] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Describe the method of assignment to trial intervention (for example, 
stratified randomisation). If assignment to trial intervention is by 
randomisation, describe when randomisation occurs relative to 
screening.  
Describe the level and method of blinding,  for example, single-blind, 
double-blind, [including Sponsor unblinded], matching placebo, double-
dummy, or open-label). Include mention of measures taken to minimise 
bias on the part of participants, investigators, and analysts.  
If applicable, describe within-trial transition rules, for example, 
transitions involving cohorts or trial parts. Dose escalation or dose-
ranging details should also be described. 
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: Trial Population 
Duplicate field in   
other sections 
264   
Page 137 of 346 
   
Term (Variable)  Randomisation 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept:  
Duplicate field in   
other sections 
265   
Term (Variable)  Method and Level of Blinding 
Data Type  List 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required/Multiple 
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Single-blind, double-blind, [including Sponsor unblinded], matching 
placebo, double-dummy, or open-label 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept:  
Duplicate field in   
other sections 
266   
Page 138 of 346 
   
Term (Variable)  Measures to Minimise Bias 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept:  
Duplicate field in   
other sections 
267   
Term (Variable)  Trial Transition Rules 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept:  
Duplicate field in   
other sections 
268   
Page 139 of 346 
   
Term (Variable)  [Method of Assignment to Trial Intervention] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Discuss important aspects of trial design, including: 
  Geographic scope of trial (for example, single-centre, multi-
centre, or multi-centre and multi-national).  
  Planned use of a Data Monitoring Committee, or similar review 
group and cross-reference Section 10.3, Committees Structure, for 
details. 
Whether an interim analysis is planned and, if so, refer to details in 
Section 9.7, Interim Analysis.. 
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
269   
Page 140 of 346 
   
Term (Variable)  Geographic Scope 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Discuss important aspects of trial design, including: 
  Geographic scope of trial (for example, single-centre, multi-
centre, or multi-centre and multi-national).  
  Planned use of a Data Monitoring Committee, or similar review 
group and cross-reference Section 10.3, Committees Structure, for 
details. 
  Whether an interim analysis is planned and, if so, refer to details 
in Section 9.7, Interim Analysis. 
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Single-centre, multi-centre, or multi-centre and multi-national 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
270   
Page 141 of 346 
   
Term (Variable)  Decentralise Process, Tools, or Features 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
271   
Term (Variable)  Committees 
Data Type  List 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required/Multiple 
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  No, Data Monitoring Committee 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
272   
Page 142 of 346 
   
Term (Variable)  Interim Analyses 
Data Type  List 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Yes, No 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
273   
Term (Variable)  Number if Interim Analyses 
Data Type  Number 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
274   
Page 143 of 346 
   
Term (Variable)  Planned Extension 
Data Type  List 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  No, planned extension Trial, long-term follow-up/registry, or post-Trial 
sample analysis or other data-related activities 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
275   
Page 144 of 346 
   
Term (Variable)  [Additional Description of Trial Design] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Protocol Synopsis / Overall Design 
other sections 
276  4.1.1  Participant Input into Design 
Term (Variable)  Participant Input into Design 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance  If applicable, describe any participant involvement in the design of the 
clinical trial and any participant suggestions implemented. 
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Participant Input into Design 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
277   
Page 145 of 346 
   
Term (Variable)  Participant Input  
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Heading 
User Guidance  If applicable, describe any participant involvement in the design of the 
clinical trial and any participant suggestions implemented. 
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
278  4.2  Rationale for Trial Design 
Term (Variable)  Rationale for Trial Design  
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Rationale for Trial Design 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
279   
Page 146 of 346 
   
Term (Variable)  [Rationale for Intervention Model] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Provide a rationale for the trial intervention model selected in Section 
4.1, Description of Trial Design. A rationale for the choice of comparator, 
if applicable, should be described separately in Section 4.2.1, Rationale 
for Comparator. 
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
280   
Term (Variable)  [Rationale for Trial Duration] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Provide a rationale that the trial duration is appropriate to show a 
reliable and relevant effect of the trial intervention per the trial 
objective(s). 
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
281   
Page 147 of 346 
   
Term (Variable)  [Rationale for Trial Duration] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Provide a rationale that the trial endpoint(s) described in Section 3, Trial 
Objectives, Endpoints, and Estimands, are clinically relevant and provide 
a reliable and valid measurement of the intended intervention effect. 
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
282   
Page 148 of 346 
   
Term (Variable)  [Interim Analysis] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  If applicable, provide a rationale for any interim analysis planned with 
respect to its purpose (for example, stopping the trial early for efficacy 
or futility) and timing. 
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
283  4.2.1  Rationale for Comparator 
Term (Variable)  Rationale for Comparator 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Rationale for Comparator 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
284   
Page 149 of 346 
   
Term (Variable)  [Rationale for Comparator] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  If applicable, provide a rationale for the type of control selected for the 
trial (for example, placebo, active drug, combination, historical). Discuss 
any known or potential problems associated with the control group 
selected in light of the specific disease and intervention(s) being studied.  
If comparators will differ by region, describe.  Describe prior studies that 
support the dose and/or dose regimen. 
Conformance  Conditional 
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: Control Mechanism 
Concept: n/a 
Duplicate field in   
other sections 
285   
Page 150 of 346 
   
286  4.2.2  Rationale for Adaptive or Novel Trial Design 
Term (Variable)  Rationale for Adaptive or Novel Trial Design 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Rationale for Adaptive or Novel Trial Design 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
287   
Page 151 of 346 
   
Term (Variable)  [Rationale for Adaptive or Novel Trial Design] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  If applicable, provide a rationale for the use of an adaptive or novel trial 
design. 
Conformance  Conditional 
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
288  4.2.3  Other Trial Design Considerations 
Term (Variable)  Other Trial Design Considerations 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Other Trial Design Considerations 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
289   
Page 152 of 346 
   
Term (Variable)  [Other Trial Design Considerations] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Discuss any additional aspects of trial design not addressed above.   
Conformance  Conditional 
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
290  4.3  Access to Trial Intervention After End of Trial 
Term (Variable)  Access to Trial Intervention After End of Trial 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Access to Trial Intervention After End of Trial 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
291   
Page 153 of 346 
   
Term (Variable)  Access to Trial Intervention After End of Trial 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  If applicable, describe any possibilities for access to trial intervention, if 
any, beyond completion of the trial.  Planned extension trials, if described above in 
Section 4.1 do not need to be repeated. 
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
292   
293  4.4  Start of Trial and End of Trial 
Term (Variable)  Start of Trial and End of Trial 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Start of Trial and End of Trial 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
294   
Page 154 of 346 
   
Term (Variable)  [Trial Start and End] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Provide definitions of the start and end of the trial. These definitions 
should consider local regulatory requirements. 
If applicable, describe any planned extension trial, long-term follow-
up/registry, or post-trial sample analysis or other data-related activities. 
Refer to Section 7.5, Access to Trial Intervention, for a description of 
plans for post-trial access to trial intervention. 
Conformance  Required  
Cardinality   
Relationship content  Trial Design  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
295   
Page 155 of 346 
   
296  5.  Trial Population 
Term (Variable)  Trial Population 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  In this section, describe the trial population. Use the following guidance 
when developing participant eligibility criteria to be listed in Section 5.3, 
Inclusion Criteria, and Section 5.4, Exclusion Criteria. 
  List the criteria necessary for participation in the trial. Ensure that 
each criterion can be easily assessed on the basis of measurable data 
and answered with yes/no responses. 
  If participants require screening, distinguish between screening 
vs enrolling participants.  Identify specific laboratory tests or clinical 
characteristics that will be used as criteria for enrollment or exclusion. If 
permitting existing medical diagnosis, imaging, genetic tests, or 
laboratory results, state any required window or acceptable test type. 
  If measures to enrich the trial population for pre-specified 
subgroups of interest are used, these should be described 
Conformance  Required  
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Trial Population 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
297   
Page 156 of 346 
   
298  5.1  Selection of Trial Population 
Term (Variable)  Selection of Trial Population 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Selection of Trial Population 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
299   
Page 157 of 346 
   
Term (Variable)  [Selection of Trial Population] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Describe the trial population selected (for example, healthy volunteers, 
adult participants, paediatric participants). Specify the population age 
range (for example, 0 to 3 months, 18 to 80 years old) and any key 
diagnostic criteria for the population (for example, acute lung injury, or 
a specific biomarker profile).  If applicable, describe similar conditions or 
diseases and their differential diagnosis. 
Conformance  Required  
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
300   
Page 158 of 346 
   
301  5.2  Rationale for Trial Population 
Term (Variable)  Rationale for Trial Population 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Rationale for Trial Population 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
302   
Page 159 of 346 
   
Term (Variable)  [Rationale for Trial Population] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Provide a rationale for the trial population ensuring that the trial 
population selected is well defined and clinically recognisable. Justify 
whether the trial intervention is to be evaluated in children, in adults 
unable to consent for themselves, other vulnerable participant 
populations, or those that may respond to the trial intervention 
differently (for example, females, elderly, hepatic or renally impaired, or 
immunocompromised participants). 
Conformance  Required  
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
303   
Page 160 of 346 
   
Term (Variable)  Individuals who do not meet criteria for trial eligibility must not be 
enrolled via protocol waivers or exemptions 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Individuals who do not meet criteria for trial eligibility must not be 
enrolled via protocol waivers or exemptions 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
304  5.3  Inclusion Criteria 
Term (Variable)  Inclusion Criteria 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Inclusion Criteria 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
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305   
Page 161 of 346 
   
Term (Variable)  To be eligible to participate in this trial, an individual must meet all the 
following criteria: 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  To be eligible to participate in this trial, an individual must meet all the 
following criteria: 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
306   
Term (Variable)  # Inclusion Criteria 
Data Type  Number 
Topic, Value or  D 
Header 
Definition  Inclusion criteria are characteristics that define the population under 
trial, for example, those criteria that every potential participant must 
satisfy, to qualify for trial entry. 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in  number consecutively, repeat for each inclusion criteria, if deleted do not 
other sections 
replace, do not duplicate 
307   
Page 162 of 346 
   
Term (Variable)   Inclusion Criteria 
Data Type  Text 
Topic, Value or   
Header 
Definition  Inclusion criteria are characteristics that define the population under 
trial, for example, those criteria that every potential participant must 
satisfy, to qualify for trial entry. 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
308  5.4  Exclusion Criteria 
Term (Variable)  Exclusion Criteria 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Exclusion Criteria 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
309   
Page 163 of 346 
   
Term (Variable)  An individual who meets any of the following criteria will be excluded 
from participation in this trial: 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  An individual who meets any of the following criteria will be excluded 
from participation in this trial: 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
310   
Page 164 of 346 
   
Term (Variable)  # Exclusion Criteria 
Data Type  Number 
Topic, Value or  D 
Header 
Definition  Exclusion criteria are characteristics that make an individual ineligible for 
trial participation 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Number consecutively, repeat for each inclusion criteria, if deleted do 
other sections 
not replace, do not duplicate 
311  5.5  Lifestyle Considerations 
Term (Variable)  Lifestyle Considerations 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Lifestyle Considerations 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
312   
Page 165 of 346 
   
Term (Variable)  [Lifestyle Considerations] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  In the following subsections, describe any restrictions during the trial 
pertaining to lifestyle and/or diet, intake of caffeine, alcohol, or tobacco, 
or physical and other activities. If not applicable, include a statement 
that no restrictions are required. 
Conformance  Required (at least one item and repeat for each item) 
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
313  5.5.1  Meals and Dietary Restrictions 
Term (Variable)  Meals and Dietary Restrictions 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Meals and Dietary Restrictions 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
314   
Page 166 of 346 
   
Term (Variable)  [Meals and Dietary Restrictions] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  If applicable, describe any restrictions on diet (for example, food and 
drink restrictions, timing of meals relative to dosing). 
Conformance  Optional (repeat for each item) 
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
315  5.5.2  Caffeine, Alcohol, Tobacco, and Other Habits 
Term (Variable)  Caffeine, Alcohol, Tobacco, and Other Habits 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Caffeine, Alcohol, Tobacco, and Other Habits 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
316   
Page 167 of 346 
   
Term (Variable)  [Caffeine, Alcohol, Tobacco, and Other Habits] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  If applicable, describe any restrictions on the intake of caffeine, alcohol, 
tobacco, or other restrictions. 
Conformance  Optional (repeat for each item) 
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
317  5.5.3  Physical Activity 
Term (Variable)  Physical Activity 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Physical Activity 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
318   
Page 168 of 346 
   
Term (Variable)  [Physical Activity]   
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  If applicable, describe any restrictions on activity (for example, in first-
in-human studies, activity may be restricted by ensuring participants 
remain in bed for 4 to 6 hours after dosing); or any other activity 
restrictions, such as on driving, heavy machinery use, or sun exposure. 
Conformance  Optional (repeat for each item) 
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
319   
320  5.5.4  Other Activity 
Term (Variable)  Other Activity   
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Other Activity 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
321   
Page 169 of 346 
   
Term (Variable)  [Other Activity]   
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  If applicable, describe restrictions on any other activity (for example, 
blood or tissue donation); or any other activity restrictions, such as on 
driving, heavy machinery use, or sun exposure. 
Conformance  Optional (repeat for each item) 
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
322  5.6  Screen Failures 
Term (Variable)  Screen failures 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Screen failures 
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
323   
Page 170 of 346 
   
Term (Variable)  [Screen Failure] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Indicate how screen failure will be handled in the trial, including 
conditions and criteria upon which rescreening is acceptable. If 
applicable, indicate the circumstances and time window under which a 
repeat procedure is allowed for screen failure relating to specific 
inclusion/exclusion criteria for the trial. 
Conformance  Required  
Cardinality   
Relationship content  Trial Population 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
324   
Page 171 of 346 
   
325  6.  Trial Intervention and Concomitant Therapy 
Term (Variable)  Trial Intervention and Concomitant Therapy 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance  In this section, describe the trial intervention being tested and any 
control product being used.  If multiple trial interventions are to be 
evaluated, Section 6.1, Description of Trial Intervention, Section 6.3, 
Dosing and Administration, and Section 6.5, Preparation, Handling, 
Storage, and Accountability should differentiate between each product. 
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Trial Intervention and Concomitant Therapy 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
326   
Page 172 of 346 
   
327  6.1  Description of Trial Intervention 
Term (Variable)  Description of Trial Intervention 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Heading 
User Guidance  Describe the intervention to be administered in each arm of the trial and 
for each period of the trial including route and mode of administration, 
dose, dosage regimen, duration of intervention, packaging, labelling, 
and storage conditions. Include information for all trial interventions 
(experimental, placebo, active comparator, sham comparator).  
The trial intervention should be designated as an investigational 
medicinal product (IMP) or non-investigational medicinal product 
(NIMP)/auxiliary medicinal product (AxMP).  
It is suggested that the trial intervention(s) be described concisely in a 
table. 
Indicate whether an additional product will be provided as part of the 
trial and its intended use (background intervention, challenge agent, 
rescue medication, diagnostic, or other). If use of an additional product 
is planned, include dosing information. Refer to approved regional 
labelling or describe any differences. 
For drug/device combination products, include details on the 
configuration and use of the device and device manufacturer. A device 
user manual may be referenced in this section 
Conformance  Required  
Cardinality   
Relationship content  Description of Trial Intervention 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Description of Trial Intervention 
Business rules  Value Allowed: Description of Trial Intervention 
Relationship: Table row headers 
Concept: n/a 
Duplicate field in   
other sections 
328   
Page 173 of 346 
   
Term (Variable)  Arm Name 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Arm Name 
Business rules  Value Allowed: Yes 
Relationship: Table header 
Concept: n/a 
Duplicate field in   
other sections 
329   
Term (Variable)  Arm Type 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Arm Type 
Business rules  Value Allowed: Yes 
Relationship: Table header 
Concept: n/a 
Duplicate field in   
other sections 
330   
Page 174 of 346 
   
Term (Variable)  Intervention Name 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Intervention Name 
Business rules  Value Allowed: Yes 
Relationship: Table Header 
Concept: n/a 
Duplicate field in   
other sections 
331   
Term (Variable)  Intervention Type 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Intervention Type 
Business rules  Value Allowed: Yes 
Relationship: Table header 
Concept: n/a 
Duplicate field in   
other sections 
332   
Page 175 of 346 
   
Term (Variable)  Use 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Use 
Business rules  Value Allowed: Yes 
Relationship: Table header 
Concept: n/a 
Duplicate field in   
other sections 
333   
Term (Variable)  IMP/NIMP 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  IMP/NIMP 
Business rules  Value Allowed: Yes 
Relationship: Table header 
Concept: n/a 
Duplicate field in   
other sections 
334   
Page 176 of 346 
   
Term (Variable)  Formulation 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Formulation 
Business rules  Value Allowed: Yes 
Relationship: Table header 
Concept: n/a 
Duplicate field in   
other sections 
335   
Term (Variable)  Unit Dose Strength 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Unit Dose Strength 
Business rules  Value Allowed: Yes 
Relationship: Table header 
Concept: n/a 
Duplicate field in   
other sections 
336   
Page 177 of 346 
   
Term (Variable)  Dose Level 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Dose Level 
Business rules  Value Allowed: Yes 
Relationship: Table header 
Concept: n/a 
Duplicate field in   
other sections 
337   
Term (Variable)  Route of Administration  
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Route of Administration 
Business rules  Value Allowed: Yes 
Relationship: Table Header 
Concept: n/a 
Duplicate field in   
other sections 
338   
Page 178 of 346 
   
Term (Variable)  Regimen/Treatment Period 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Regimen/Treatment Period 
Business rules  Value Allowed: Yes 
Relationship: Table Heading 
Concept: n/a 
Duplicate field in   
other sections 
339   
Term (Variable)  Arm Name 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Text 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
340   
Page 179 of 346 
   
Term (Variable)  Arm Type 
Data Type  Pick List 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Experimental, Active Comparator, Placebo Comparator, Sham 
Comparator, No Intervention 
Business rules  Value Allowed: Yes 
Relationship: Relates to Arm and intervention formulation dosage 
Concept: n/a 
Duplicate field in  Once for each arm 
other sections 
Replicate for number of arms 
341   
Term (Variable)  Intervention Name 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: Relates to arm 
Concept: n/a 
Duplicate field in  Relates to Arm 
other sections 
342   
Page 180 of 346 
   
Term (Variable)  Intervention Type 
Data Type  Pick List 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Drug, device, biologic/vaccine, procedure/surgery, radiation, behavioral, 
genetic, dietary supplement, combination product, dietary 
Business rules  Value Allowed: Yes 
Relationship: Relates to arm and intervention formulation dosage 
Concept: n/a 
Duplicate field in  Replicate for all interventions in the arm 
other sections 
343   
Term (Variable)  Use 
Data Type  Pick List 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Experimental, Placebo, rescue medicine, background treatment, 
challenge agent, diagnostic, systemic, all prescribed 
Business rules  Value Allowed: Yes 
Relationship: Relates to arm and intervention formulation dosage 
Concept: n/a 
Duplicate field in  Replicate for all interventions in the arm 
other sections 
344   
Page 181 of 346 
   
Term (Variable)  IMP/NIMP 
Data Type  Pick List 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  IMP, NIMP 
Business rules  Value Allowed: Yes 
Relationship: Relates to arm and intervention formulation dosage 
Concept: n/a 
Duplicate field in  Replicate for all interventions in the arm 
other sections 
345   
Term (Variable)  Formulation 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Reference IDMP Codes 
Business rules  Value Allowed: Yes 
Relationship: Relates to arm and intervention formulation dosage 
Concept: n/a 
Duplicate field in  Replicate for all interventions in the arm 
other sections 
346   
Page 182 of 346 
   
Term (Variable)  Unit Dose Strength 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Reference IDMP Codes 
Business rules  Value Allowed: n/a 
Relationship: Relates to Arm and intervention formulation dosage 
Concept: n/a 
Duplicate field in  Replicate for all interventions in the arm 
other sections 
347   
Term (Variable)  Dose Level 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Reference IDMP Codes 
Business rules  Value Allowed: n/a 
Relationship: Relates to arm and intervention formulation dosage 
Concept: n/a 
Duplicate field in  Replicate for all interventions in the arm 
other sections 
348   
Page 183 of 346 
   
Term (Variable)  Route of Administration  
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Reference IDMP Codes 
Business rules  Value Allowed: Yes 
Relationship: Relates to arm and intervention formulation dosage 
Concept: n/a 
Duplicate field in  Replicate for all interventions in the arm 
other sections 
349   
Term (Variable)  Regimen/Treatment Period 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Regimen/Treatment Period 
Business rules  Value Allowed: Yes 
Relationship: Relates to arm and intervention formulation dosage  
Concept: n/a 
Duplicate field in  Replicate for all interventions in the arm 
other sections 
350   
Page 184 of 346 
   
Term (Variable)  [Additional Text, if Needed] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a  
Concept: n/a 
Duplicate field in   
other sections 
351  6.2  Rationale for Trial Intervention 
Term (Variable)  Rationale for Trial intervention 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Rationale for Trial intervention 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
352   
Page 185 of 346 
   
Term (Variable)  Rationale for Trial intervention 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Provide a rationale for the selection of the dose(s) or dose range, the 
route of administration, and dosing regimen (including starting dose, 
dose titration, dose interval) of the trial intervention and any control 
product. This rationale should include relevant results from previous 
preclinical and clinical studies that support selection of the dose and 
regimen.  Include any information about age or sex-based 
pharmacokinetic or pharmacodynamic differences known from previous 
studies. If applicable, justify any differences in specifications, dose 
regimen, or therapeutic use relative to approved labelling.   
Include a rationale for prospective dose adjustments incorporated in the 
trial, if any; for example, as a result of interim analysis. 
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
353   
Page 186 of 346 
   
354  6.3  Dosing and Administration 
Term (Variable)  Dosing and Administration 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Dosing and Administration 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
355   
Page 187 of 346 
   
Term (Variable)  Dosing and Administration 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Describes the details of dosing and administration, schedule, as well as 
any specific instructions as listed below.  
User Guidance  Describe the detailed procedures for administration of each participants 
dose of trial intervention and control product. This may include the 
timing of dosing (for example, time of day, interval), the duration (for 
example, the length of time trial participants will be administered the 
trial intervention), the planned route of administration (for example, 
oral, nasal, intramuscular), and the timing of dosing relative to meals.  
Include any specific instructions to trial participants about when or how 
to prepare and take the dose(s) and how delayed or missed doses 
should be handled.  
For an individual participant, describe dose modifications allowed.  State 
any minimum period required before a participants dose might be raised 
to the next higher dose or dose range. Include whether it is permissible 
to start and stop treatment and how dose reductions (if permitted) are 
to be managed. 
Discussion of dose escalation or cohort expansion as part of the overall 
trial design should be covered in Section 4.2 (Trial Design). 
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
356   
Page 188 of 346 
   
357  6.3.1  Trial Intervention Dose Modification 
Term (Variable)  Trial Intervention Dose Modification 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Trial Intervention Dose Modification 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
358   
Page 189 of 346 
   
Term (Variable)  Dose Modification 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Describes the conditions under which a dose modification will be made, 
particularly with regard to failure to respond or to toxic or untoward 
changes in stipulated indicators. 
User Guidance  If applicable, the protocol should state the conditions under which a dose 
modification will be made for an individual participant, particularly 
regarding failure to respond or to toxic or untoward changes in 
stipulated indicators. This section can also include discussion of dose 
titration.  Do not include information on stopping trial intervention for 
individual participants due to safety/other reasons as this is detailed in 
Section 7, Discontinuation of Trial Intervention and Participant 
Discontinuation/Withdrawal from the Trial. 
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
359   
Page 190 of 346 
   
360  6.4  Treatment of Overdose 
Term (Variable)  Treatment of Overdose 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Treatment of Overdose 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
361   
Page 191 of 346 
   
Term (Variable)  Treatment of Overdose 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Specifies what is meant by trial intervention overdose and any known 
antidote or therapies. 
User Guidance  Although clinical experience with overdose is often limited in early 
phases of development, provide any available project-specific guidance 
and information; however, ensure consistency with and avoid 
unnecessary duplication with any overdose information in the 
Investigators Brochure /package insert. Cross-reference these 
documents if appropriate. Refer to the approved product label of the 
comparator (as applicable) for advice on overdose. 
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
362   
Page 192 of 346 
   
363  6.5  Preparation, Handling, Storage and Accountability 
Term (Variable)  Preparation, Handling, Storage, and Accountability 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Preparation, Handling, Storage, and Accountability 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
364  6.5.1  Preparation of Trial Intervention 
Term (Variable)  Preparation of Trial Intervention 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Preparation of Trial Intervention 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
365   
Page 193 of 346 
   
Term (Variable)  [Trial Intervention Preparation] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Describe any preparation of the trial intervention and control product 
and by whom. 
User Guidance  Discuss the maximum hold time once thawed/mixed, if appropriate, 
before administration. Include thawing, diluting, mixing, and 
reconstitution/preparation instructions in this section, as applicable. For 
drug/device combination products, include any relevant assembly or use 
instructions. 
If the instructions are lengthy or complicated, it is acceptable to 
reference the label (if applicable) or include them as a separate 
document(s) provided to the site (for example, a pharmacy manual). If 
instructions are provided to the site as a separate document(s), this 
should be noted in here. 
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  [insert Trial Intervention Preparation text] 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
366   
Page 194 of 346 
   
367  6.5.2  Handling and Storage of Trial Intervention 
Term (Variable)  Handling and Storage of Trial Intervention 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Storage and Handling of Trial Intervention 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
368   
Page 195 of 346 
   
Term (Variable)  Trial Intervention Storage and Handling 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Describes storage and handling requirements (for example, protection 
from light, temperature, humidity) for the trial intervention and control 
product. 
User Guidance  For studies in which multi-dose vials are utilised, provide additional 
information regarding stability and expiration time after initial use (for 
example, the seal is broken). 
[Trial Intervention Storage and Handling] 
State how the trial intervention and control product will be provided to 
the Investigator. If applicable, describe the kits, packaging, or other 
material of the trial intervention for blinding purposes. 
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  [insert Trial Intervention Storage and Handling text] 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
369   
Page 196 of 346 
   
370  6.5.3  Accountability of Trial Intervention 
Term (Variable)  Accountability of Trial Intervention 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Accountability of Trial Intervention 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
371   
Page 197 of 346 
   
Term (Variable)  Accountability 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Describe the method by which the accountability will be achieved, 
including trial intervention will be distributed and related details, 
including: 
  how and by whom the trial intervention will be distributed 
  participation of a drug repository or pharmacy, if applicable,  
  plans for disposal or return of unused product, and 
  expectations for reconciliation. 
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  [Accountability Text] 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
372   
Page 198 of 346 
   
373  6.6  Participant Assignment, Randomisation and Blinding 
Term (Variable)  Participant Assignment, Randomisation and Blinding 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Participant Assignment, Randomisation and Blinding 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
374  6.6.1  Participant Assignment 
Term (Variable)  Participant Assignment 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Participant Assignment 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
375   
Page 199 of 346 
   
Term (Variable)  Participant Assignment 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Describes the method of assigning participants to trial intervention 
User Guidance  Describe the method of assigning participants to trial intervention 
without being so specific that blinding or randomisation might be 
compromised. If assignment to trial intervention is by randomisation, 
describe when randomisation occurs relative to screening. If participants 
will be assigned to intervention sequences as in a cross-over trial, then 
describe these sequences.  
If adaptive randomisation or other methods of covariate 
balancing/minimisation are employed, include a cross-reference to the 
methods of analysis in Section 9, Statistical Considerations. As 
applicable, details regarding the implementation of procedures to 
minimise bias should be described. 
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
376   
Page 200 of 346 
   
377  6.6.2  Randomisation 
Term (Variable)  Randomisation 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Randomisation 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
378   
Page 201 of 346 
   
Term (Variable)  Randomisation 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Describe the randomisation procedures (for example, central 
randomisation procedures), the method used to generate the 
randomisation schedule (for example, computer generated), the source 
of the randomisation schedule (for example, Sponsor, Investigator, or 
other), and whether or not IVRS/IWRS will be used. 
User Guidance  To maintain the integrity of the blinding, do not include the block size. 
Describe the use and validation of any computer systems or programs in 
randomisation, stratification, and unblinding. 
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
379   
Page 202 of 346 
   
380  6.6.3  Blinding and Unblinding 
Term (Variable)  Blinding 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Blinding 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
381   
Page 203 of 346 
   
Term (Variable)  Blinding 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Describe efforts to ensure that the trial intervention and control products 
are as indistinguishable as possible. 
User Guidance  Plans for the maintenance of trial randomisation codes and appropriate 
blinding for the trial should be discussed. Procedures for planned and 
unplanned breaking of randomisation codes should be provided.  
If the trial allows for some investigators or other designated staff to 
remain unmasked (for example, to allow them to adjust medication), the 
means of maintaining the blinding for other investigators or staff should 
be explained. Measures to prevent unblinding by laboratory 
measurements, if used, should be described. 
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
382   
Page 204 of 346 
   
Term (Variable)  Emergency Unblinding 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Emergency Unblinding 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
383   
Term (Variable)  Emergency Unblinding 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Describes the criteria for breaking the trial mask (blind) or participant 
code. 
User Guidance  Discuss the circumstances in which the blinding would be broken for an 
individual or for all participants (for example, for SAEs) and who has 
responsibility. Include the procedure for emergency unblinding such as 
via IVRS/IWRS or code envelopes as well as documentation of 
unblinding. Indicate to whom the intentional and unintentional 
unblinding should be reported. 
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
384   
Page 205 of 346 
   
385  6.7  Trial Intervention Compliance 
Term (Variable)  Trial Intervention Compliance 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Trial Intervention Compliance 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
386   
Term (Variable)  Additional Trial Intervention Compliance 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Describe measures to ensure and document dosing information and trial 
intervention compliance (for example, accountability records, diary 
cards, concentration measurements). 
User Guidance  Include a discussion of what documents are mandatory to complete (for 
example, participant drug log) and what source data/records will be 
used to document trial intervention compliance 
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
387   
Page 206 of 346 
   
388  6.8  Concomitant Therapy 
Term (Variable)  Concomitant Therapy 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Concomitant Therapy 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
389   
Page 207 of 346 
   
Term (Variable)  Concomitant Therapy 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Describes how allowed concomitant therapy might affect the outcome 
(for example, drug-drug interaction, direct effects on the trial endpoints) 
and how the independent effects of concomitant and trial interventions 
could be ascertained. 
User Guidance  This section should be consistent with the medication restrictions in the 
inclusion/exclusion criteria previously listed.  Describe the data (for 
example, dose and frequency, and any changes) that will be recorded 
related to permitted concomitant medications, supplements, 
complementary and alternative therapies, treatments, and/or 
procedures, and include details about when the information will be 
collected (for example, screening, all trial visits).   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
390   
Page 208 of 346 
   
391  6.8.1  Prohibited Concomitant Therapy 
Term (Variable)  Prohibited Concomitant Therapy 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Prohibited Concomitant Therapy 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
392   
Page 209 of 346 
   
Term (Variable)  Prohibited Concomitant Therapy 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Describes any prohibited concomitant therapy. 
User Guidance  Include content in this section if applicable, otherwise note as not 
applicable.  
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
393  6.8.2  Permitted Concomitant Therapy 
Term (Variable)  Permitted Concomitant Therapy 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Permitted Concomitant Therapy 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
394   
Page 210 of 346 
   
Term (Variable)  Permitted Concomitant Therapy 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Describes any permitted concomitant therapy. 
User Guidance  Include content in this section if applicable, otherwise note as not 
applicable.  
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
395  6.8.3  Rescue Therapy 
Term (Variable)  Rescue Therapy 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Rescue Therapy 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
396   
Page 211 of 346 
   
Term (Variable)  Rescue Therapy 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Describes the circumstances under which use of rescue therapy is 
permitted. 
User Guidance  List all medications, treatments, and/or procedures which may be 
provided during the trial for rescue therapy and provide relevant 
instructions about the administration of rescue medications. Describe the 
circumstances under which use of rescue therapy is permitted. 
If administration of rescue therapy leads to the temporary 
discontinuation of trial intervention or a participants withdrawal from 
the trial, refer to Section 7, Discontinuation of Trial Intervention and 
Participant Discontinuation/Withdrawal from the Trial. 
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
397   
Page 212 of 346 
   
398  6.8.4  Other Therapy 
Term (Variable)  Other Therapy 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Other Therapy 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
399   
Term (Variable)  Other Therapy 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Describes the circumstances under which use of other noninvestigational 
or auxiliary therapy are permitted, e.g. challenge agents. 
User Guidance  Include content in this section if applicable.  
Conformance  Required  
Cardinality   
Relationship content  Trial Intervention and Concomitant Therapy 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
400   
Page 213 of 346 
   
401  7.  Discontinuation of Trial Intervention and Participant Withdrawal 
402  from Trial 
Term (Variable)  Discontinuation of Trial Intervention and Participant Withdrawal from 
Trial 
Data Type   
Topic, Value or  H 
Header 
Definition   
User Guidance  This section must align with the intercurrent events introduced in 
Section 3, Trial Objectives, Endpoints, and Estimands, and the treatment 
described in Section 6 Trial Intervention and Concomitant Therapy. 
Conformance  Required  
Cardinality   
Relationship content  Discontinuation of Trial Intervention 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Discontinuation of Trial Intervention and Participant Withdrawal from 
Trial 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
403   
Page 214 of 346 
   
404  7.1  Discontinuation of Trial Intervention 
Term (Variable)  Discontinuation of Trial Intervention 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  Discontinuation of trial intervention for a participant occurs when trial 
intervention is stopped earlier than the protocol planned duration 
Conformance  Required  
Cardinality   
Relationship content  Discontinuation of Trial Intervention 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Discontinuation of Trial Intervention 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
405  7.1.1  Criteria for Permanent Discontinuation of Trial Intervention 
Term (Variable)  Criteria for Discontinuation of Trial Intervention 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Discontinuation of Trial Intervention 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Criteria for Discontinuation of Trial Intervention 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
406   
Page 215 of 346 
   
Term (Variable)  Criteria for Permanent Discontinuation of Trial Intervention 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Criterias for discontinuation of a participant from trial intervention. 
User Guidance  Describe the criteria for discontinuation of a participant from trial 
intervention, carefully evaluating which are appropriate for the 
participant population and therapy being studied. 
Specify whether participants who discontinue trial intervention can or 
cannot continue the trial (continue trial visits). Refer to the SoA for 
assessments to be performed at the time of and following 
discontinuation of trial intervention 
Conformance  Required  
Cardinality   
Relationship content  Discontinuation of Trial Intervention 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
407   
Page 216 of 346 
   
408  7.1.2  Temporary Discontinuation or Interruption of Trial Intervention 
Term (Variable)  Temporary Discontinuation or Interruption of Trial Intervention 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Discontinuation of Trial Intervention 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Temporary Discontinuation or Interruption of Trial Intervention 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
409   
Page 217 of 346 
   
Term (Variable)  Temporary Discontinuation/Interruption of Trial Intervention 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Specifics criteria for interrupting trial intervention 
User Guidance  Describe  
  the criteria for temporary discontinuation or interruption of trial 
intervention for an individual participant  
  what to do and which restrictions still apply if the participant 
needs to temporarily discontinue or interrupt trial intervention  
  whether they will continue in the trial, and  
  whether all, or specify which, assessments will be performed for 
the stated duration of the trial. 
Details of any rechallenge or restart after a safety-related event should 
be included in Section 7.1.3, Rechallenge. 
Conformance  Required 
Cardinality   
Relationship content  Discontinuation of Trial Intervention 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
410   
Page 218 of 346 
   
411  7.1.3  Rechallenge 
Term (Variable)  Rechallenge 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Discontinuation of Trial Intervention 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Rechallenge 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
412   
Term (Variable)  Rechallenge 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Describe the criteria for rechallenge/restarting trial intervention, how to 
perform rechallenge, number of rechallenges allowed during the trial, 
and whether all, or specify which, assessments will be performed for the 
stated duration of the trial. 
If rechallenge is not allowed, state this. 
Conformance  Required  
Cardinality   
Relationship content  Discontinuation of Trial Intervention 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
413   
Page 219 of 346 
   
414  7.2  Participant Withdrawal from the Trial 
Term (Variable)  Participant Withdrawal from Trial 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Discontinuation of Trial Intervention 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Participant Withdrawal from Trial 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
415   
Term (Variable)  Participant Withdrawal from Trial 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Describe the criteria for participant withdrawal from the trial. 
Conformance  Required  
Cardinality   
Relationship content  Discontinuation of Trial Intervention 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
416   
Page 220 of 346 
   
417  7.3  Lost to Follow-Up 
Term (Variable)  Lost to Follow-Up 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Discontinuation of Trial Intervention 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Lost to Follow-Up 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
418   
Term (Variable)  Lost to Follow-Up 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Describe how the trial will define and address participants who are lost 
to follow-up to help limit the amount and impact of missing data. 
Describe the nature and duration of follow-up, as appropriate. 
Conformance  Required 
Cardinality   
Relationship content  Discontinuation of Trial Intervention 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
419   
Page 221 of 346 
   
420  7.4  Trial Stopping Rules 
Term (Variable)  Trial Stopping Rules 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Discontinuation of Trial Intervention 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Trial Stopping Rules 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
421   
Term (Variable)  Trial Stopping Rules 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  If applicable, describe or refer to any trial-specific stopping rules 
described in the protocol, including guidance on when the trial should be 
stopped for safety reasons, when a cohort or dose escalation should be 
terminated, and/or when a given treatment arm should be terminated. 
Conformance  Required  
Cardinality   
Relationship content  Discontinuation of Trial Intervention 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
422   
Page 222 of 346 
   
423  8.  Trial Assessments and Procedures 
Term (Variable)  Trial Assessments and Procedures 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance    Describe the assessments and procedures required during each 
phase of the trial. Provide details that are not already presented in the 
SoA, taking care not to duplicate information. 
  Describe methods, training, tools, instruments/questionnaires, 
calibration methods, etc. that will be used to record and assess data and 
ensure consistency across centres and participants. Include instructions 
on timing/conditions of assessments and if a specifically qualified person 
should be performing these assessments. Describe whether centralised 
readings and measurements will be utilised. Describe procedures to be 
used to maintain the blind. 
  Reference the literature for the validation of 
scales/instruments/questionnaires/assays. 
  Instructions or protocols for specialised tests may be presented in 
an appendix or a separate document and cross-referenced. 
  If the trial includes qualitative interviews, describe these 
evaluations. 
  If COA measures are utilised, include instructions for the 
investigators per local guidance. All COA parameters should be fully 
integrated into the appropriate sections of the protocol; separate COA 
sections should not be created in the protocol. 
  Include minimums and limits for procedures (for example, 
volume of blood draws, number of imaging procedures/biopsies, 
radiation exposure, etc.) if appropriate to the trial. 
Conformance  Required  
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Trial Assessments and Procedures 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
424   
Page 223 of 346 
   
425  8.1  Screening/Baseline Assessments and Procedures 
Term (Variable)  Screening/Baseline Assessments and Procedures 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  This section describes assessments and procedures that are unique to 
screening/baseline (for example, collection of data on participant 
characteristics, assessments/procedures performed for the purpose of 
determining eligibility or for stratification) in this section. 
 
Conformance  Required 
Cardinality   
Relationship content  Trial Assessment and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Screening/Baseline Assessments and Procedures 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
426   
Page 224 of 346 
   
Term (Variable)  Screening/Baseline Assessments and Procedures 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  This section describes assessments and procedures that are unique to 
screening/baseline (for example, collection of data on participant 
characteristics, assessments/procedures performed for the purpose of 
determining eligibility or for stratification) in this section. 
Conformance   
Optional/Repeated 
Cardinality   
Relationship content  Screening/Baseline Assessments and Procedures 
from ToC 
Link to objective endpoint or estimand 
representing the 
protocol hierarchy 
Relationship  Trial Assessment and Procedures 
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: potential controlled terminology 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeat for each procedure 
other sections 
427  8.2  Efficacy Assessments and Procedures 
Term (Variable)  Efficacy Assessments and Procedures 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  This section describes efficacy assessments and procedures 
 
Conformance  Required 
Cardinality   
Relationship content  Trial Assessment and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Efficacy Assessments and Procedures 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
428   
Page 225 of 346 
   
Term (Variable)  Efficacy Assessments and Procedures 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  This section describes efficacy assessments and procedures  
Conformance   
Optional/Repeated 
Cardinality   
Relationship content  Trial Assessment and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship  Efficacy Assessments and Procedures 
(reference to high 
Link to objective endpoint or estimand 
level conceptual 
model) 
Value   
Business rules  Value Allowed: potential controlled terminology 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeat for each procedure 
other sections 
429   
Page 226 of 346 
   
430  8.3  Safety Assessments and Procedures 
Term (Variable)  Safety Assessments and Procedures 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance 
This section describes safety assessments and procedures in this 
section. Level 3 headings can be added as needed. 
  Identify any non-investigator party responsible for evaluation of 
laboratory or other safety assessments (for example, Sponsor or 
external Independent Data Monitoring Committee). 
  Include guidelines for the management of relevant laboratory or 
other safety assessment abnormalities. 
 
Conformance  Required 
Cardinality   
Relationship content  Trial Assessment and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Efficacy Assessments and Procedures 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
431   
Page 227 of 346 
   
Term (Variable)  Safety Assessments and Procedures 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance 
This section describes safety assessments and procedures in this 
section. Level 3 headings can be added as needed. 
  Identify any non-investigator party responsible for evaluation of 
laboratory or other safety assessments (for example, Sponsor or 
external Independent Data Monitoring Committee). 
  Include guidelines for the management of relevant laboratory or 
other safety assessment abnormalities. 
 
Conformance   
Optional/ Repeated 
Cardinality   
Relationship content  Trial Assessment and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship  Safety Assessments and Procedures 
(reference to high 
Link to objective endpoint or estimand 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Potential controlled terminology 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeat for each procedure 
other sections 
432   
Page 228 of 346 
   
433  8.3.1  Physical Examination 
Term (Variable)  Physical Examination 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Physical Examination 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
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other sections 
434   
Page 229 of 346 
   
Term (Variable)  Physical Examination 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Include any specific instructions with respect to the collection and 
interpretation of physical examinations. 
Conformance   
Optional/Repeated 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship  Physical Examination 
(reference to high 
Link to objective endpoint or estimand 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Potential controlled terminology 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeat for each procedure 
other sections 
435  8.3.2  Vital Signs 
Term (Variable)  Vital Signs 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Vital Signs 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
436   
Page 230 of 346 
   
Term (Variable)  Vital Signs 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance    Carefully consider which vital signs (if any) should be measured to 
ensure that only essential data are collected 
  Include any specific instructions with respect to the collection and 
interpretation of vital signs (for example, order). If orthostatic vital 
signs will be assessed, include instructions for supine and standing 
blood pressure and pulse measurements 
  Select the standard methods of vital sign collection as appropriate 
for the countries in which the trial will be conducted 
  For studies requiring sensitive blood pressure monitoring (for 
example, if blood pressure decrease or increase is an anticipated 
effect), include details on device calibration requirements or 
frequency of measuring. 
Conformance  Optional/Repeated 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship  Vital signs 
(reference to high 
Link to objective endpoint or estimand 
level conceptual 
model) 
Value   
Business rules  Value Allowed: potential controlled terminology 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeat for each procedure 
other sections 
437   
Page 231 of 346 
   
438  8.3.3  Electrocardiograms 
Term (Variable)  Electrocardiograms 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Electrocardiograms 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
439   
Page 232 of 346 
   
Term (Variable)  Electrocardiograms 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance    Specify if the ECG is for screening purposes only. 
  Include any specific instructions for the collection, interpretation, 
and archiving of ECGs (for example, time points relative to dosing with 
trial treatment or other evaluations). 
  Indicate whether single or triplicate ECGs will be collected at each 
time point. If triplicate ECGs will be collected, provide necessary details. 
  Indicate whether ECGs will be analysed at a central or local 
laboratory. 
High-quality ECG data should be collected if the goal is to assess the 
effects of trial treatment on ECG intervals such as the QT interval. Such 
ECG data may be required to meet regulatory authority expectations for 
a thorough ECG assessment (for example, as outlined in ICH E14) or to 
better assess a cardiac conduction signal from previous nonclinical or 
clinical studies. 
Conformance  Optional/Repeated 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship  Electrocardiograms 
(reference to high 
Link to objective endpoint or estimand 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Potential controlled terminology 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeat for each procedure 
other sections 
440   
Page 233 of 346 
   
441  8.3.4  Clinical Laboratory Assessments 
Term (Variable)  Clinical Laboratory Assessments 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Clinical Laboratory Assessments 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
442   
Page 234 of 346 
   
Term (Variable)  Clinical Laboratory Assessments 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance    For multicenter studies in participants who are patients, make 
every effort to ensure routine laboratory safety assessments are 
performed by a central laboratory. If local laboratory assessments are 
required, these must be stated clearly in the protocol. Provisions should 
be in place to allow for the acceptance of local laboratory data (even if a 
central laboratory is used). Sponsor databases should be set up 
appropriately for the reporting of data from both central and local 
laboratories. Consult with the data management representative for 
language to be included on how data should be reported to the sponsor 
if a local laboratory is used. 
  Specify if the use of local laboratories is allowed in cases where 
initiation of trial treatment or safety follow-up is time-sensitive and the 
central laboratory results will not be available before the need to begin 
trial treatment or other actions that need to be taken for safety reasons.  
  Specify any special instructions for screening samples. 
  Specify which laboratory parameters should be included in each 
panel (for example, for hematology, chemistry, urinalysis). List only 
those that will be analysed for the trial. Confirm lists and blood volumes 
before finalising the protocol. 
Conformance  Optional/Repeated 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship  Clinical Laboratory Assessments 
(reference to high 
Link to objective endpoint or estimand 
level conceptual 
model) 
Value   
Business rules  Value Allowed: potential controlled terminology 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeat for each procedure 
other sections 
443   
Page 235 of 346 
   
444  8.3.5  Suicidal Ideation and Behaviour Risk Monitoring 
Term (Variable)  Suicidal Ideation and Behaviour Risk Monitoring 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Suicidal Ideation and Behaviour Risk Monitoring 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
445   
Page 236 of 346 
   
Term (Variable)  Suicidal Ideation and Behaviour Risk Monitoring 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  If clinical trials meet any of the criteria requiring suicidal ideation and 
behavior risk monitoring by the guidance/guideline in each region, 
include any specific instructions with respect to the collection and 
interpretation of the assessment. 
Conformance  Required 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  [Trial Intervention] is considered to be central nervous system (CNS)-
active. In addition, there have been some reports of {suicidal ideation or 
behavior as reported in the product label} when it has been given to 
some participants with {certain conditions}. The sponsor considers it 
important to monitor for such events before and during this clinical trial. 
OR 
[Trial Intervention] is considered to be an {antidepressant/ antiepileptic/ 
CNS-active trial treatment}. There has been some concern that 
{antidepressants/ antiepileptics/ some CNS-active trial treatments} may 
be associated with an increased risk of suicidal ideation or behavior 
when given to some participants with {major depressive disorder/ 
bipolar disorder/ epilepsy/ certain conditions}. Although this trial 
treatment or other similar drugs in this class have not been shown to be 
associated with an increased risk of suicidal thinking or behavior when 
given to {healthy volunteers/this participant population}, the sponsor 
considers it important to monitor for such events before or during this 
clinical trial. 
Business rules  Value Allowed: Potential controlled terminology 
Relationship: n/a 
Concept: n/a 
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446   
Page 237 of 346 
   
447  8.4  Adverse Events and Serious Adverse Events 
Term (Variable)  Adverse Events and Serious Adverse Events 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Adverse Events and Serious Adverse Events 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
448  8.4.1  Definitions of AE and SAE 
Term (Variable)  Definition of Adverse Events and Serious Adverse Events 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content   
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Definition of Adverse Events and Serious Adverse Events 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
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449   
Page 238 of 346 
   
Term (Variable)  [AE Definition] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content   
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Definition of Adverse Event 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
450   
Term (Variable)  [SAE Definition] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content   
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Definition of Serious Adverse Event 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
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451   
Page 239 of 346 
   
Term (Variable)  Additional details and clarifications for AEs and SAEs are in Appendices 
12.1 and 12.2 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content   
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Additional details and clarifications for AEs and SAEs are in Appendices 
12.1 and 12.2 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
452  8.4.2  Time Period and Frequency for Collecting AE and SAE 
453  Information 
Term (Variable)  Time Period and Frequency for collection AE and SAE Information 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Time Period and Frequency for collection AE and SAE Information 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
454   
Page 240 of 346 
   
Term (Variable)  Time period and frequency for collecting AEs and SAEs 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Specify the start and ending time periods for collecting AEs and SAEs.  
Consider the following factors when deciding on the collection time 
period: 
  Available information on how long the trial intervention remains 
active in the participant 
  How long it may remain active/inactive in the participant and 
potentially be transferable to a fetus 
  How long it takes for AEs and SAEs to peak (e.g. is there an 
anticipated cumulative effect of dosing and when is this likely to occur) 
  Known late effects (e.g. secondary malignancies that will require 
active monitoring) 
  Trial design 
  If collection will start when the ICF is signed to capture baseline 
rates 
Conformance  Required  
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
455   
Page 241 of 346 
   
456  8.4.3  Identifying AEs and SAEs 
Term (Variable)  Identifying AEs and SAEs 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Identifying AEs and SAEs 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
457   
Term (Variable)  Identifying AEs and SAEs 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Specifies the method(s) used to identify AEs and SAEs. 
User Guidance  To avoid bias, Open-ended and non leading verbal questioning of the 
participant is the preferred method. However, for studies in which the 
participants are not always able to provide valid verbal responses to 
open ended questions, another method may be required. 
Conformance  Required 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
458   
Page 242 of 346 
   
459  8.4.4  Recording of AEs and SAEs 
Term (Variable)  Recording of AEs and SAEs 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Duplicate field in   
other sections 
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Recording of AEs and SAEs 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
460   
Term (Variable)  Recording of AEs and SAEs 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Specifies the Investigators actions for recording AEs, including the final 
AE outcome. 
User Guidance   
Conformance  Required  
Cardinality   
Duplicate field in   
other sections 
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
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other sections 
461   
Page 243 of 346 
   
Term (Variable)  Further details on assessing severity and causality of AEs and SAEs are 
in Appendices 12.3 and 12.4 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Specifies the Investigators actions for recording AEs, including the final 
AE outcome. 
User Guidance   
Conformance  Required  
Cardinality   
Duplicate field in   
other sections 
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Further details on assessing severity and causality of AEs and SAEs are 
in Appendices 12.3 and 12.4 
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
462  8.4.5  Follow-up of AEs and SAEs 
Term (Variable)  Follow-up of AEs and SAEs 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Follow-up of AEs and SAEs 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
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463   
Page 244 of 346 
   
Term (Variable)  Follow-up of AEs and SAEs 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Specify the procedures for follow-up of AEs and SAEs until they are 
resolved or considered stable.  Include the assessment tools that will be 
used to monitor the events and the duration of follow-up after 
appearance of the events.  Specify any procedures to be used for studies 
in which death is not an endpoint. 
Conformance  Required  
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
464   
Page 245 of 346 
   
465  8.4.6  Reporting of SAEs 
Term (Variable)  Reporting of SAEs 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Duplicate field in   
other sections 
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Reporting of SAEs 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
466   
Page 246 of 346 
   
Term (Variable)  Reporting of SAEs 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Specify the SAE reporting method (e.g., an electronic data collection tool 
or a paper CRF). 
Conformance  Required  
Cardinality   
Duplicate field in   
other sections 
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
467  8.4.7  Regulatory Reporting Requirements for SAEs 
Term (Variable)  Regulatory Reporting Requirements for SAEs 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Regulatory Reporting Requirements for SAEs 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
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468   
Page 247 of 346 
   
Term (Variable)  Regulatory Reporting 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Specify: 
  The Sponsors legal/regulatory responsibilities to report SAEs to 
regulatory authorities, ethics committees, and investigators. 
  The investigators responsibilities for promptly reporting SAEs to 
the Sponsor to allow the Sponsor to meet their responsibilities. 
Conformance  Required  
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
469   
470  8.4.8  Serious and Unexpected Adverse Reaction Reporting 
Term (Variable)  Serious and Unexpected Adverse Reaction Reporting 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Assessment and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Serious and Unexpected Adverse Reaction Reporting 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
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471   
Page 248 of 346 
   
Term (Variable)  Serious and Unexpected Adverse Reaction Reporting 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Include this section, if applicable.  
Conformance  Required  
Cardinality   
Relationship content  Trial Assessment and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
472  8.4.9  Adverse Events of Special Interest 
Term (Variable)  Adverse Events of Special Interest 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Assessment and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Adverse Events of Special Interest 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
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473   
Page 249 of 346 
   
Term (Variable)  Adverse Events of Special Interest 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Include this section, if applicable. 
Specify any Adverse Events of Special Interest (AESI): 
  Other events that merit reporting to the Sponsor, trial leadership, 
IRB, and regulatory agencies (for example, secondary malignancies in 
oncology studies). 
  Other reportable events not already included in the previous 
sections, such as cardiovascular and death events, medical device 
incidents (including malfunctions), laboratory test abnormalities, and 
trial intervention overdose. 
Include the following for each AESI: 
  The definition of the event. Specify the MedDRA preferred terms 
to use to report the AESI. 
  If it is a measurable quantity, specify how will the measurement 
be done. 
If it is a clinical event, specify how will it be confirmed. 
Conformance  Required  
Cardinality   
Relationship content  Trial Assessment and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
474   
Page 250 of 346 
   
475  8.4.10  Disease-related Events or Outcomes Not Qualifying as AEs or 
476  SAEs 
Term (Variable)  Disease-related Events or Outcomes Not Qualifying as AEs or SAEs 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Disease-related Events or Outcomes Not Qualifying as AEs or SAEs 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
477   
Term (Variable)  Disease-related Events or Outcomes Not Qualifying as AEs or SAEs 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Specify any Disease-Related Events (DREs), disease-related outcomes, 
or both that will not be reported as AEs or SAEs (for example, seizures 
in anticonvulsant studies). 
Conformance  Required  
Cardinality   
Relationship content  Trial Assessment and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
478   
Page 251 of 346 
   
479  8.5  Pregnancy and Postpartum Information 
Term (Variable)  Pregnancy and Postpartum Information 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Pregnancy and Postpartum Information 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
480  8.5.1  Participants Who Become Pregnant During the Trial 
Term (Variable)  Participants Who Become Pregnant During Trial 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Trial Assessment and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Participants Who Become Pregnant During Trial 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
481   
Page 252 of 346 
   
Term (Variable)  Participants Who Become Pregnant During Trial 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Specify the assessments to be performed, type and duration of 
monitoring, and what information will be collected for a participant who 
becomes pregnant during the trial (for example, recording and reporting 
to the Sponsor, postpartum follow-up, trial intervention discontinuation 
or continuation, or trial withdrawal). For postpartum follow-up, include 
the time period (for example, initial child development) with the 
justification. 
If exposure to trial intervention during breastfeeding is applicable, 
specify the assessments to be performed, type and duration of 
monitoring, and what information will be collected for both the 
participant and child. 
Specify that pregnancy is not an AE, unless a negative or consequential 
outcome occurs in the participant or child/foetus. If the negative event 
meets the seriousness criteria, then this is considered an SAE (for 
example, spontaneous abortion, foetal death, stillbirth, congenital 
anomalies, ectopic pregnancy, or pre-eclampsia) and reported per 
Section 8.1.5, Reporting of SAEs. 
Conformance  Optional 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
482   
Page 253 of 346 
   
483  8.5.2  Participants Whose Partners Become Pregnant 
Term (Variable)  Participants Whose Partners Become Pregnant 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Participants Whose Partners Become Pregnant 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
484   
Page 254 of 346 
   
Term (Variable)  Participants Whose Partners Become Pregnant 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Specify: 
  If the Investigator will attempt to collect pregnancy information 
for a participants partner, who becomes pregnant while the participant 
is in the trial. 
  The assessments to be performed, type and duration of 
monitoring, and what information will be collected. 
Conformance  Optional 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
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485   
Page 255 of 346 
   
486  8.6  Medical Device Product Complaints for Drug/Device Combination 
487  Products 
Term (Variable)  Medical Device Product Complaints for Drug/Device Combination 
Products 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required  
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Medical Device Product Complaints for Drug/Device Combination 
Products 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
488   
489  8.6.1  Definition of Medical Device Product Complaints 
Term (Variable)  Definition of Medical Device Complaints 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Trial Assessment and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
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490   
Page 256 of 346 
   
Term (Variable)  Definition of Medical Device Compliance 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Add this section for drug/device combination products; otherwise, omit 
it. 
Conformance  Optional 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  The definitions and procedures in this section comply with ISO 14155 
and European Medical Device Regulation (MDR) 2017/745 for clinical 
device research (if applicable). 
Both the Investigator and the Sponsor will comply with all local medical 
device product complaint reporting requirements. 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
491   
492  8.6.2  Recording of Medical Device Product Complaints 
Term (Variable)  Recording of medical Device Product Complaints 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Recording of Medical Device Product Complaints 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
493   
Page 257 of 346 
   
Term (Variable)  Recording of Medical Device Product Complaints 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  When a product compliant occurs, the Investigator will review relevant 
documentation (for example, diary cards, memory aids, hospital 
progress notes, laboratory reports, and diagnostics reports) related to 
the event. 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
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494   
Page 258 of 346 
   
495  8.6.3  Time Period and Frequency for Collecting Medical Device 
496  Product Complaints 
Term (Variable)  Time Period and Frequency for Collecting Medical Device Product 
Complaints 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Trial Assessments and Procedures  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Time Period and Frequency for Collecting Medical Device Product 
Complaints 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
497   
Term (Variable)  Time Period and Frequency for Collection Medical Device Product 
Complaints 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Trial Assessments and Procedures  
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Time Period and Frequency for Collection Medical Device Product 
Complaints 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
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498   
Page 259 of 346 
   
499  8.6.4  Follow-Up of Medical Device Product Complaints 
Term (Variable)  Follow-up of Medical Device Product Complaints 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Follow-up of Medical Device Product Complaints 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
500   
Term (Variable)  Follow-up of Medical Device Product Complaints 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Specify how medical device product complaints will be followed until 
resolved or considered stable.  Specify the procedures for their follow-
up, including what assessment tools will be used to monitor the events 
and the duration of follow-up after appearance of the events. 
Conformance  Optional 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed:  
Relationship: n/a 
Concept: n/a 
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501   
Page 260 of 346 
   
502  8.6.5  Regulatory Reporting Requirements for Medical Device Product 
503  Complaints 
Term (Variable)  Regulatory Reporting Requirements for Medical Device Product 
Complaints 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Optional 
Cardinality   
Relationship content  Trial Assessment and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Regulatory Reporting Requirements for Medical Device Product 
Complaints 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
504   
Page 261 of 346 
   
Term (Variable)  Regulatory Reporting Requirements for Medical Device Product 
Complaints 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  This section addresses the Investigators responsibilities for reporting 
Medical Device Product Complaints (e.g., within 24 hours).  Sponsors 
have additional regulatory responsibilities that are not described in this 
template. 
Conformance  Optional 
Cardinality   
Relationship content  Trial Assessment and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
505   
506  8.7  Pharmacokinetics 
Term (Variable)  Pharmacokinetics 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Pharmacokinetics 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
507   
Page 262 of 346 
   
Term (Variable)  Pharmacokinetics 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance    Insert text as appropriate for this trial. If population PK will be 
included, provide appropriate text. If PK will not be part of the trial, 
include a statement to this effect.   
  Describe any trial treatment concentrations to be measured and 
the sample collection times relative to dosing. Samples of plasma, urine, 
or other fluids may be taken for the purpose of measuring compliance, 
adjusting dose, or determining if a therapeutic window exists. This 
section of the protocol will be written in collaboration with the 
appropriate PK representatives and will contain information about 
sampling times, sample volume, sample handling procedures, assay 
methods, etc. Specific sample collection and processing including 
retention time instructions can be described in an Appendix and cross-
referenced. 
  Indicate definitions for the PK parameters (for example, area 
under the curve [AUC], maximum observed concentration [Cmax], time 
to Cmax [Tmax], half-life [T12], volume of distribution [Vd], clearance 
[CL]) of interest and how they will be calculated. Consult with the PK 
representative for this information 
  Describe sampling time relative to ingestion of food, posture, and 
possible effects of concomitant medications/alcohol/caffeine/nicotine. 
  Describe the biological sample(s) collected (blood, urine, or other 
such as breath, saliva, biopsies, etc.), the handling of samples, and the 
assay method including references to published and/or internal assay 
validation documentation. 
  Specify other factors that are important in assessing the PK of 
the trial treatment (for example, soluble circulating receptors, renal or 
hepatic function) and the plan for measuring these factors. 
Conformance   
Optional/Repeated 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship  Pharmacokinetics  
(reference to high 
Assessments and Procedures 
level conceptual 
Link to objective endpoint or estimand 
model) 
Value   
Business rules  Value Allowed: potential controlled terminology 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeat for each assessment 
other sections 
508   
Page 263 of 346 
   
509  8.8  Genetics 
Term (Variable)  Genetics 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Genetics 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
510     
Page 264 of 346 
   
511   
Term (Variable)  Genetics 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Refer to ICH E15 and E18 as needed. 
Contact the appropriate sponsor functional area representatives to 
ensure that appropriate pharmacogenomic trial design text is included 
throughout the protocol.  
See the appropriate guidelines/templates from the sponsor functional 
area representatives (for example, standard attachments for shipping 
and handling of laboratory samples). Dependent upon the volume of 
these attachments, they may be added to the protocol in an additional 
section or provided in supplementary documents that will accompany the 
protocol. 
Conformance   
Optional/Repeated 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship  Genetic Assessments and Procedures 
(reference to high 
Link to objective endpoint or estimand 
level conceptual 
model) 
Value   
Business rules  Value Allowed: potential controlled terminology 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeat for each analysis 
other sections 
512   
Page 265 of 346 
   
513  8.9  Biomarkers 
Term (Variable)  Biomarkers 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Biomarkers 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
514   
Page 266 of 346 
   
Term (Variable)  Biomarkers 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Refer to ICH E15 and E18 as needed. 
If biomarkers will be evaluated: 
  Include analyses (e.g, ribonucleic acid [RNA], serum, plasma, or 
other soluble markers). 
  Indicate any additional analyses, such as flow cytometry, 
histology, serology, immunogenicity, or histochemical analyses. 
  Ensure language describing how long the samples will be stored 
and how they will be destroyed is included in an ICF and any sample 
handling manuals. 
  If instructions for collection of samples are complex, then 
consider including them in an appendix rather than the main text of 
protocol. 
  Specify whether optional or required (both here and in the SoA). 
Required samples must be based on a protocol objective. 
  To distinguish between different types of biomarker samples, 
include the following for each sample, as appropriate: 
o  Indicate if residual samples. 
o  Indicate the type of sample (e.g., serum, plasma, tissue, bone 
marrow aspirate) and volume of fluid or sample amount required and 
any other special instructions 
o  Indicate the purpose of the sample (e.g., participant eligibility, 
exploratory research, RNA analysis). 
o  Indicate the timing of collection (e.g., screening, disease 
progression); do not give specific time points (e.g., Week 4 or Cycle 4) 
as this information will be provided in the SoA. 
o  Indicate the biomarkers that will be studied. 
Conformance  Optional/Repeated 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship  Biomarker Assessments and Procedures 
(reference to high 
Link to objective endpoint or estimand 
level conceptual 
model) 
Value   
Business rules  Value Allowed: potential controlled terminology 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeat for each biomarker 
other sections 
515   
Page 267 of 346 
   
516  8.10  Immunogenicity Assessments 
Term (Variable)  Immunogenicity Assessments 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance 
Include any specific instructions for the collection of samples and 
interpretation of immunogenicity. If immunogenicity assessments are 
included within Efficacy Assessments or Safety Assessments, cross-
reference to that section. 
Conformance  Required 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Immunogenicity Assessments 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
517   
Page 268 of 346 
   
Term (Variable)  Immunogenicity Assessments 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Optional/Repeated 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship  Immunogenicity Assessments and Procedures 
(reference to high 
Link to objective endpoint and estimand 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeat for each procedure 
other sections 
518  8.11  Medical Resource Utilisation and Health Economics 
Term (Variable)  Medical Resource Utilization and Health Economics 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance   
Conformance  Required/Required 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Medical Resource Utilization and Health Economics 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
519   
Page 269 of 346 
   
Term (Variable)  Medical Resource Utilization and Health Economics 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Describes the health outcome measures, collection method (for example, 
diary, physician interview), and participant burden. 
User Guidance  If this section is not applicable, include a statement to this effect. 
Health Economics/Medical Resource Utilization and Health Economics 
parameters are not evaluated in this trial. 
This section does not apply to Patient Reported Outcomes [PROs] (for 
PROs cross reference the instructions in the efficacy and safety 
sections). 
Include this section only for any value evidence and outcomes 
assessment not included in either the efficacy or safety sections. 
Conformance  Optional/ Repeated 
Cardinality   
Relationship content  Trial Assessments and Procedures 
from ToC 
representing the 
protocol hierarchy 
Relationship  Medical Resource Utilisation and Health Economics Assessments and 
(reference to high 
Procedures 
level conceptual 
Link to objective endpoint or estimand 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeat for each evidence and outcome 
other sections 
520   
Page 270 of 346 
   
521  9.  Statistical Considerations 
Term (Variable)  Statistical Considerations 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance 
Ensure that the data analysis complies with ICH E9 and ICH E9(R1). 
 
Conformance  Required 
Cardinality   
Relationship content  Statistical Considerations 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Statistical Considerations 
Business rules  Value Allowed: Y 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
522   
Page 271 of 346 
   
Term (Variable)  Statistical Considerations 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Section Heading 
User Guidance 
Ensure that the data analysis complies with ICH E9 and ICH E9(R1). 
In general, all relevant data collected in the trial should be considered in 
this statistical considerations section.  
Provide a statement with regard to when the primary analyses will be 
conducted. For example: The analysis will be conducted on all subject 
data at the time the trial ends.   
Conformance  Required 
Cardinality   
Relationship content  Statistical Considerations 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Statistical Considerations 
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
523   
Page 272 of 346 
   
524  9.1  Analysis Sets 
Term (Variable)  Analysis Sets 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance 
Analysis sets to support each analysis will be specified here and 
described in the Statistical Analysis Plan. 
Conformance  Required 
Cardinality   
Relationship content  Analysis Sets 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Analysis Sets 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
525   
Term (Variable)  Analysis Datasets 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Detailed description of all efficacy assessments presented in the SoA  
User Guidance 
Analysis sets to support each analysis will be specified here and 
described in the Statistical Analysis Plan. 
Conformance  Required 
Cardinality   
Relationship content  Analysis Sets 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
526   
Page 273 of 346 
   
527  9.2  Analyses Supporting Primary Objective(s) 
Term (Variable)  Analysis Supporting Primary Objective(s) 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance  This section introduces the Statistical Analysis Plan, with the detail to be 
provided in the subsequent subsections. This includes describing the 
methods for defining the estimate in alignment with how the estimands 
are defined. Sensitivity analyses should be aligned with how the 
estimands and estimators are defined.  
Conformance  Required 
Cardinality   
Relationship content  Analysis Supporting Primary Objective(s) 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Analysis Supporting Primary Objective(s) 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
528   
Page 274 of 346 
   
Term (Variable)  Analysis Supporting Primary Objective(s) 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  This section introduces the Statistical Analysis Plan, with the detail to be 
provided in the subsequent subsections. This includes describing the 
methods for defining the estimate in alignment with how the estimands 
are defined. Sensitivity analyses should be aligned with how the 
estimands and estimators are defined.  
User Guidance 
Analysis sets to support each analysis will be specified here and 
described in the Statistical Analysis Plan. 
Conformance  Required/Repeated 
Cardinality   
Relationship content  Analysis Supporting Primary Objective(s) 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
529   
Page 275 of 346 
   
530  9.2.1  Statistical Model, Hypothesis, and Method of Analysis 
Term (Variable)  Statistical Model, Hypothesis, and Method of Analysis 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  Ensure that the statistical hypothesis/model (and corresponding 
assumptions)/analysis is aligned with the primary estimand(s). 
For all applicable objectives (e.g. primary, secondary), under the 
appropriate header, state the null and alternative hypotheses, including 
the pre-planned type 1 error, or alternative criteria to define trial 
success and relevant operating characteristics if appropriate. Describe 
the statistical model used and the factors that will be included 
(covariates and interactions) and any rules for handling these factors 
(for example, pooling of centres). If applicable, state and discuss any 
adjustments to account for multiplicity.  
If modelling and simulation methods are to be used, please describe the 
model (inputs and outputs), the underlying assumptions, and the 
method of model fitting. 
Conformance  Required 
Cardinality   
Relationship content  Statistical Considerations/Analyses Supporting Primary 
from ToC  Objective(s)/Statistical Model, Hypothesis, and Method of Analysis 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
531   
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Term (Variable)  Statistical Model, Hypothesis, and Method of Analysis 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Ensure that the statistical hypothesis/model (and corresponding 
assumptions)/analysis is aligned with the primary estimand(s). 
For all applicable objectives (e.g. primary, secondary), under the 
appropriate header, state the null and alternative hypotheses, including 
the pre-planned type 1 error, or alternative criteria to define trial 
success and relevant operating characteristics if appropriate. Describe 
the statistical model used and the factors that will be included 
(covariates and interactions) and any rules for handling these factors 
(for example, pooling of centres). If applicable, state and discuss any 
adjustments to account for multiplicity.  
If modelling and simulation methods are to be used, please describe the 
model (inputs and outputs), the underlying assumptions, and the 
method of model fitting. 
Conformance  Required/Repeated 
 
Cardinality   
Relationship content  Statistical Considerations/Analyses Supporting Primary 
from ToC  Objective(s)/Statistical Model, Hypothesis, and Method of Analysis 
representing the 
protocol hierarchy 
Relationship  For each primary estimand as related to secondary endpoint combination 
(reference to high 
level conceptual 
model) 
Value  Statistical Model, Hypothesis, and Method of Analysis 
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
532   
Page 277 of 346 
   
Term (Variable)  Statistical Model, Hypothesis, and Method of Analysis 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Ensure that the statistical hypothesis/model (and corresponding 
assumptions)/analysis is aligned with the primary estimand(s). 
For all applicable objectives (e.g. primary, secondary), under the 
appropriate header, state the null and alternative hypotheses, including 
the pre-planned type 1 error, or alternative criteria to define trial 
success and relevant operating characteristics if appropriate. Describe 
the statistical model used and the factors that will be included 
(covariates and interactions) and any rules for handling these factors 
(for example, pooling of centres). If applicable, state and discuss any 
adjustments to account for multiplicity.  
If modelling and simulation methods are to be used, please describe the 
model (inputs and outputs), the underlying assumptions, and the 
method of model fitting. 
Conformance  Required/Repeated 
 
Cardinality   
Relationship content  Statistical Considerations/Analyses Supporting Primary 
from ToC  Objective(s)/Statistical Model, Hypothesis, and Method of Analysis 
representing the 
protocol hierarchy 
Relationship  For all applicable primary objectives sate the null state the null and 
(reference to high  alternative hypotheses, including the pre-planned type 1 error, or 
level conceptual  alternative criteria to define Trial success and relevant operating 
model)  characteristics if appropriate. Describe the statistical model used and the 
factors that will be included (covariates and interactions) and any rules 
for handling these factors (for example, pooling of centres). If 
applicable, state and discuss any adjustments to account for multiplicity. 
Value  Statistical Model, Hypothesis, and Method of Analysis 
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
533   
Page 278 of 346 
   
Term (Variable)  Statistical Model, Hypothesis, and Method of Analysis 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Ensure that the statistical hypothesis/model (and corresponding 
assumptions)/analysis is aligned with the primary estimand(s). 
For all applicable objectives (e.g. primary, secondary), under the 
appropriate header, state the null and alternative hypotheses, including 
the pre-planned type 1 error, or alternative criteria to define trial 
success and relevant operating characteristics if appropriate. Describe 
the statistical model used and the factors that will be included 
(covariates and interactions) and any rules for handling these factors 
(for example, pooling of centres). If applicable, state and discuss any 
adjustments to account for multiplicity.  
If modelling and simulation methods are to be used, please describe the 
model (inputs and outputs), the underlying assumptions, and the 
method of model fitting. 
Conformance  Optional/Repeated 
 
Cardinality   
Relationship content  Statistical Considerations/Analyses Supporting Primary 
from ToC  Objective(s)/Statistical Model, Hypothesis, and Method of Analysis 
representing the 
protocol hierarchy 
Relationship  Modelling and simulation methods are to be used, please describe the 
(reference to high  model (inputs and outputs), the underlying assumptions, and the 
level conceptual  method of model fitting 
model) 
Value  Statistical Model, Hypothesis, and Method of Analysis 
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
534   
Page 279 of 346 
   
535  9.2.2  Handling of Intercurrent Events of Primary Estimand(s) 
Term (Variable)  Handling of Intercurrent Events of Primary Estimand(s) 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance 
For each intercurrent event of the primary estimand(s) (Section 3.1, 
Estimand[s] for the Primary Objective[s]), explain how data will be 
handled for the statistical analysis in line with the primary estimand. The 
handling of intercurrent events in statistical analysis should be aligned 
with the specific estimand strategies being used.  
This section should avoid repetition with prior sections with more detail 
here on rationale and handling the data rather than repeating the 
guidance from the preceding sections.  
Conformance  Required 
Cardinality   
Relationship  Statistical Considerations/Analyses Supporting Primary Objective(s / 
content from ToC  Handling of Intercurrent Events of Primary Estimand(s) 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
536   
Page 280 of 346 
   
Term (Variable)  Handling of Intercurrent Events of Primary Estimand(s) 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance 
For each intercurrent event of the primary estimand(s) (Section 3.1, 
Estimand[s] for the Primary Objective[s]), explain how data will be 
handled for the statistical analysis in line with the primary estimand. The 
handling of intercurrent events in statistical analysis should be aligned 
with the specific estimand strategies being used.  
This section should avoid repetition with prior sections with more detail 
here on rationale and handling the data rather than repeating the 
guidance from the preceding sections.  
Conformance  Required/Repeated 
 
Cardinality   
Relationship  Statistical Considerations/Analyses Supporting Primary Objective(s / 
content from ToC  Handling of Intercurrent Events of Primary Estimand(s) 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
537   
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538  9.2.3   Handling of Missing Data 
Term (Variable)  Handling of Missing Data 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance 
This section should describe how missing data will be dealt with. Refer to 
the E9(R1) addendum when estimand framework is used. 
The protocol should describe how missing data will be handled (for 
example, type of imputation technique, if any, and provide justification)   
In cases where the Primary Objective is related to safety, this section 
should also be completed. It may also be helpful to include additional 
statements regarding handling of missing data in general for other 
important efficacy or safety endpoints or this information can be 
included in the analysis of secondary endpoint section below.  
 
Conformance  Required 
Cardinality   
Relationship content  Statistical Considerations/Analyses Supporting Primary Objective(s / 
from ToC  Handling of Missing Data 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in  For each estimand 
other sections 
539   
Page 282 of 346 
   
Term (Variable)  Handling of Missing Data 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance 
This section should describe how missing data will be dealt with. Refer to 
the E9(R1) addendum when estimand framework is used. 
The protocol should describe how missing data will be handled (for 
example, type of imputation technique, if any, and provide justification)   
In cases where the Primary Objective is related to safety, this section 
should also be completed. It may also be helpful to include additional 
statements regarding handling of missing data in general for other 
important efficacy or safety endpoints or this information can be 
included in the analysis of secondary endpoint section below.  
Conformance  Required/Repeated 
Cardinality   
Relationship content  Statistical Considerations/Analyses Supporting Primary Objective(s / 
from ToC  Handling of Missing Data 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
540  9.2.4  Sensitivity Analysis 
Term (Variable)  Sensitivity Analysis 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  Sensitivity analyses are a series of analyses conducted with the intent to 
explore the robustness of inferences from the main estimator to 
deviations from its underlying modelling assumptions and limitations in 
the data.  
Conformance  Required  
Cardinality   
Relationship content  Statistical Considerations/Analyses Supporting Primary 
from ToC  Objective(s)/Sensitivity Analysis 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Page 283 of 346 
   
Business rules  Value Allowed: yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
541   
Term (Variable)  Sensitivity Analysis 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Sensitivity analyses are a series of analyses conducted with the intent to 
explore the robustness of inferences from the main estimator to 
deviations from its underlying modelling assumptions and limitations in 
the data. 
Conformance  Required 
Cardinality   
Relationship content   Statistical Considerations/Analyses Supporting Primary 
from ToC  Objective(s)/Sensitivity Analysis 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
542  9.2.5  Supplementary Analysis 
Term (Variable)  Supplementary Analysis 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  Describe any supplementary analysis if applicable. 
 
Conformance  Required  
Cardinality   
Relationship content  Statistical Considerations/Analyses Supporting Primary 
from ToC  Objective(s)/Supplementary Analysis 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Supplementary Analysis 
Business rules  Value Allowed: yes 
Relationship: n/a 
Concept: n/a 
 
 
Page 284 of 346 
   
Duplicate field in   
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543   
Term (Variable)  Supplementary Analysis 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Describe any supplementary analysis if applicable. 
 
Conformance  Required  
Cardinality   
Relationship content  Statistical Considerations/Analyses Supporting Primary 
from ToC  Objective(s)/Supplementary Analysis 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
544   
Page 285 of 346 
   
545  9.3  Analysis Supporting Secondary Objective(s) 
Term (Variable)  Analysis Supporting Secondary Objective(s) 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance  This section should focus on estimands for Secondary Objectives. 
In this section describe the statistical analysis, handling of intercurrent 
events, handling of missing data, and if applicable, sensitivity analysis 
corresponding to each secondary estimand.  
Conformance  Required 
Cardinality   
Relationship content  Statistical Considerations/Analysis Supporting Secondary Objective(s) 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Analysis Supporting Secondary Objective(s) 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
546   
Page 286 of 346 
   
Term (Variable)  Statistical Models, Hypothesis and method Analysis 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  This section should focus on estimands for Secondary Objectives. 
In this section describe the statistical analysis, handling of intercurrent 
events, handling of missing data, and if applicable, sensitivity analysis 
corresponding to each secondary estimand.  
Conformance  Required/Repeated 
Cardinality   
Relationship content  Analysis Supporting Secondary Objective(s) 
from ToC 
representing the 
protocol hierarchy 
Relationship  For each secondary  estimand each statistcal hypothese/model (and 
(reference to high 
corresponding assumptions)/analysis 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
547   
Page 287 of 346 
   
Term (Variable)  Statistical Models, Hypothesis and method Analysis 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  This section should focus on estimands for Secondary Objectives. 
In this section describe the statistical analysis, handling of intercurrent 
events, handling of missing data, and if applicable, sensitivity analysis 
corresponding to each secondary estimand.  
Conformance  Required/Repeated 
Cardinality   
Relationship content  Analysis Supporting Secondary Objective(s) 
from ToC 
representing the 
protocol hierarchy 
Relationship  For all applicable Secondary objectives sate the null state the null and 
(reference to high 
alternative hypotheses, including the pre-planned type 1 error, or 
level conceptual 
alternative criteria to define Trial success and relevant operating 
model) 
characteristics if appropriate. Describe the statistical model used and the 
factors that will be included (covariates and interactions) and any rules 
for handling these factors (for example, pooling of centres). If 
applicable, state and discuss any adjustments to account for multiplicity. 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
548   
Page 288 of 346 
   
Term (Variable)  Handling of Intercurrent events and Method Analysis 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  This section should focus on estimands for Secondary Objectives. 
In this section describe the statistical analysis, handling of intercurrent 
events, handling of missing data, and if applicable, sensitivity analysis 
corresponding to each secondary estimand.  
Conformance  Required/Repeatable 
Optional/Repeatable 
Cardinality   
Relationship content  Analysis Supporting Secondary Objective(s) 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
549   
Page 289 of 346 
   
Term (Variable)  Statistical Models, Hypothesis and method Analysis 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  This section should focus on estimands for Secondary Objectives. 
In this section describe the statistical analysis, handling of intercurrent 
events, handling of missing data, and if applicable, sensitivity analysis 
corresponding to each secondary estimand.  
Conformance  Optional/Repeated 
Cardinality   
Relationship content  Analysis Supporting Secondary Objective(s) 
from ToC 
representing the 
protocol hierarchy 
Relationship  Secondary modelling and simulation methods are to be used, please 
(reference to high 
describe the model (inputs and outputs), the underlying assumptions, 
level conceptual 
and the method of model fitting 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
550   
Page 290 of 346 
   
Term (Variable)  Handling of Intercurrent events and Method Analysis 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  This section should focus on estimands for Secondary Objectives. 
In this section describe the statistical analysis, handling of intercurrent 
events, handling of missing data, and if applicable, sensitivity analysis 
corresponding to each secondary estimand.  
Conformance  Required/Repeated 
Cardinality   
Relationship content  Analysis Supporting Secondary Objective(s) 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
551   
Page 291 of 346 
   
Term (Variable)  Handling of Missing Data 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  This section should focus on estimands for Secondary Objectives. 
In this section describe the statistical analysis, handling of intercurrent 
events, handling of missing data, and if applicable, sensitivity analysis 
corresponding to each secondary estimand.  
Conformance  Required/Repeated 
Cardinality   
Relationship content  Analysis Supporting Secondary Objective(s) 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
552   
Page 292 of 346 
   
553  9.4  Analysis of Exploratory Objective(s) 
Term (Variable)  Analysis of Exploratory Objectives 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance 
Analyses Supporting Tertiary/Exploratory Endpoint(s) 
Conformance  Required 
Cardinality   
Relationship content  Statistical Considerations/ Analysis of Exploratory Endpoint(s) 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Analysis of Exploratory Endpoint(s) 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
554   
Page 293 of 346 
   
Term (Variable)  Analysis Supporting Tertiary/Exploratory Objectives(s) 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  This section should focus on estimands for Secondary Objectives. 
In this section describe the statistical analysis, handling of intercurrent 
events, handling of missing data, and if applicable, sensitivity analysis 
corresponding to each secondary estimand.  
 
Conformance  Required/Repeated 
Cardinality   
Relationship content  Analysis Supporting Tertiary/Exploratory Objective(s) 
from ToC 
representing the 
protocol hierarchy 
Relationship  Exploratory endpoint combination 
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeat as related to tertiary/exploratory endpoint combination 
other sections 
555   
Page 294 of 346 
   
556  9.5  Safety Analyses 
Term (Variable)  Safety Analyses 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Statistical Considerations / Safety Analyses 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
557   
Term (Variable)  Safety Analyses 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Statistical Considerations / Safety Analyses 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
558   
Page 295 of 346 
   
559  9.6  Other Analyses 
Term (Variable)  Other Analyses 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Statistical Considerations / Other Analyses 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Other Analyses 
Business rules  Value Allowed: yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
560   
Term (Variable)  Other Analyses 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Statistical Considerations / Other Analyses 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
561   
Page 296 of 346 
   
562  9.7  Interim Analyses 
Term (Variable)  Interim Analyses 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Statistical Considerations / Interim Analyses 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Interim Analyses 
Business rules  Value Allowed: yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
563   
Term (Variable)  Interim Analyses 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required/Repeated 
Cardinality   
Relationship content  Statistical Considerations / Interim Analyses 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in  For each interim 
other sections 
564   
Page 297 of 346 
   
565  9.8  Sample Size Determination 
Term (Variable)  Sample Size Determination 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  This section should detail the methods used for the determination of the 
sample size and a reference to tables or statistical software used to carry 
out the calculation. Sufficient information should be provided so that the 
sample size calculation can be reproduced or described. 
If the planned sample size is not derived statistically, then this should be 
explicitly stated along with a rationale for the intended sample size (for 
example, exploratory nature of pilot studies; pragmatic considerations 
for trials in rare diseases). 
Conformance  Required 
Cardinality   
Relationship content  Statistical Considerations / Sample Size Determination 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Sample Size Determination 
Business rules  Value Allowed: yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
566   
Page 298 of 346 
   
567  9.9  Protocol Deviations 
Term (Variable)  Protocol Deviations 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Statistical Considerations / Sample Size Determination 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Protocol Deviations  
Business rules  Value Allowed: yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
568   
Term (Variable)  Protocol Deviations Plans 
Data Type  Text 
Topic, Value or  D 
Header   
Definition   
User Guidance 
Conformance  Required 
 
Cardinality 
Relationship content  Statistical Considerations / Sample Size Determination 
from ToC 
representing the 
protocol hierarchy   
Relationship 
(reference to high 
level conceptual 
model)   
Value 
Business rules  Value Allowed: yes 
Relationship: n/a 
Concept: n/a 
 
Duplicate field in 
other sections 
569   
Page 299 of 346 
   
570  10.  General Considerations: Regulatory, Ethical, and Trial Oversight  
Term (Variable)  General Considerations: Regulatory, Ethical, and Trial Oversight 
Considerations 
Data Type   
Topic, Value or   
Header 
Definition   
User Guidance   
Conformance   
Cardinality   
Relationship content   
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed:  
Relationship:  
Concept:  
Duplicate field in   
other sections 
571   
Page 300 of 346 
   
572  10.1  Regulatory and Ethical Considerations 
Term (Variable)  Regulatory and Ethical Considerations 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance 
List the prevailing ethical, legal, and regulatory guidelines that will be 
applied throughout the trial. 
This trial will be conducted in accordance with the protocol and with the 
following: 
  Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines  
  ICH Good Clinical Practice (GCP) Guidelines  
  Applicable laws and regulations  
  {insert additional as needed} 
List the investigators and sponsors responsibilities in this regard. 
Investigator Responsibilities 
[Investigator Responsibilities] 
Sponsor Responsibilities 
[Sponsor Responsibilities] 
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Regulatory, Ethical, and Trial Oversight 
from ToC 
Considerations 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Regulatory and Ethical Considerations 
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
573   
Page 301 of 346 
   
Term (Variable)  Regulatory and Ethical Considerations 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance 
List the prevailing ethical, legal, and regulatory guidelines that will be 
applied throughout the trial. 
This trial will be conducted in accordance with the protocol and with the 
following: 
  Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines  
  ICH Good Clinical Practice (GCP) Guidelines  
  Applicable laws and regulations  
  {insert additional as needed} 
List the investigators and sponsors responsibilities in this regard. 
Investigator Responsibilities 
[Investigator Responsibilities] 
Sponsor Responsibilities 
[Sponsor Responsibilities] 
Conformance  Required/Repeatable 
Required/Repeatable 
Cardinality   
Relationship content  General Considerations: Regulatory, Ethical, and Trial Oversight 
from ToC 
Considerations / Regulatory and Ethical Considerations 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
 
Note: This field can contain a text value 
Duplicate field in   
other sections 
574   
Page 302 of 346 
   
Term (Variable) 
Investigator Responsibilities 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance 
List the prevailing ethical, legal, and regulatory guidelines that will be 
applied throughout the trial. 
This trial will be conducted in accordance with the protocol and with the 
following: 
  Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines  
  ICH Good Clinical Practice (GCP) Guidelines  
  Applicable laws and regulations  
  {insert additional as needed} 
List the investigators and sponsors responsibilities in this regard. 
Investigator Responsibilities 
[Investigator Responsibilities] 
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Regulatory, Ethical, and Trial Oversight 
from ToC 
Considerations / Regulatory and Ethical Considerations 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value 
Investigator Responsibilities 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
575   
Page 303 of 346 
   
Term (Variable) 
Investigator Responsibilities 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance 
List the prevailing ethical, legal, and regulatory guidelines that will be 
applied throughout the trial. 
This trial will be conducted in accordance with the protocol and with the 
following: 
  Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines  
  ICH Good Clinical Practice (GCP) Guidelines  
  Applicable laws and regulations  
  {insert additional as needed} 
List the investigators and sponsors responsibilities in this regard. 
Investigator Responsibilities 
[Investigator Responsibilities] 
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Regulatory, Ethical, and Trial Oversight 
from ToC 
Considerations / Regulatory and Ethical Considerations 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value 
 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
576   
Page 304 of 346 
   
Term (Variable) 
Sponsor Responsibilities 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance 
List the prevailing ethical, legal, and regulatory guidelines that will be 
applied throughout the trial. 
This trial will be conducted in accordance with the protocol and with the 
following: 
  Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines  
  ICH Good Clinical Practice (GCP) Guidelines  
  Applicable laws and regulations  
  {insert additional as needed} 
List the investigators and sponsors responsibilities in this regard. 
Sponsor Responsibilities 
[Sponsor Responsibilities] 
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Regulatory, Ethical, and Trial Oversight 
from ToC 
Considerations / Regulatory and Ethical Considerations 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value 
Sponsor Responsibilities 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
577   
Page 305 of 346 
   
Term (Variable) 
Sponsor Responsibilities 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance 
List the prevailing ethical, legal, and regulatory guidelines that will be 
applied throughout the trial. 
This trial will be conducted in accordance with the protocol and with the 
following: 
  Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines  
  ICH Good Clinical Practice (GCP) Guidelines  
  Applicable laws and regulations  
  {insert additional as needed} 
List the investigators and sponsors responsibilities in this regard. 
Sponsor Responsibilities 
[Sponsor Responsibilities] 
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Regulatory, Ethical, and Trial Oversight 
from ToC 
Considerations / Regulatory and Ethical Considerations 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value 
 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
578   
Page 306 of 346 
   
579  10.2  Committees 
Term (Variable)  Committees 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  Briefly describe the administrative structure for the trial (for example, 
Internal Review Committee/Internal Review Forum, Steering Committee, 
Expert Advisory Committee, Data Monitoring Committee or Data Safety 
Monitoring Board). Note that specific details are not required. 
 
[Committees Structure] 
 
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Regulatory, Ethical, and Trial Oversight 
from ToC 
Considerations / Committees Structure 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Committees 
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
 
 Specific details are not required 
Duplicate field in   
other sections 
580   
Page 307 of 346 
   
Term (Variable)  Committees Structure 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Briefly describe the administrative structure for the trial (for example, 
Internal Review Committee/Internal Review Forum, Steering Committee, 
Expert Advisory Committee, Data Monitoring Committee or Data Safety 
Monitoring Board). Note that specific details are not required. 
[Committees Structure] 
Conformance  Required/Repeated 
Cardinality   
Relationship content  General Considerations: Regulatory, Ethical, and Trial Oversight 
from ToC 
Considerations / Committees Structure 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
 
Specific details are not required 
Duplicate field in  For each committee 
other sections 
581   
Page 308 of 346 
   
582  10.3  Informed Consent Process  
Term (Variable)  Informed Consent Process 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance  Include the primary ethical concerns of this trial. Consider the key 
elements of the informed consent process, including any special 
concerns and how addressed (for example, assent, capacity, legally 
acceptable representative). 
[Informed Consent Process] 
If enrolment in the trial may occur during an emergency in which the 
participant or their legally authorised representative is not able or 
available to give consent, describe the consent process.   
[Emergency Consent Process] 
Rescreening 
If participants can be rescreened, add the text to state whether the 
participant needs to complete a new consent.  Screen failure and 
rescreening should be clearly defined in the protocol, with cross-
reference to those definitions. 
[Consent Requirements for Rescreening] 
If participants will be asked to consent to optional exploratory research 
using the remainder of mandatory samples, include text that addresses 
the use of remaining samples for optional exploratory research. 
[Additional ICF text for Use of Remaining Samples in Optional 
Exploratory Research] 
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Regulatory, Ethical, and Trial Oversight 
from ToC 
Considerations / Informed Consent Process 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Informed Consent Process 
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
583   
Page 309 of 346 
   
Term (Variable)  Informed Consent Process 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Include the primary ethical concerns of this trial. Consider the key 
elements of the informed consent process, including any special 
concerns and how addressed (for example, assent, capacity, legally 
acceptable representative). 
[Informed Consent Process]-Required/Required 
If enrollment in the trial may occur during an emergency in which the 
participant or their legally authorised representative is not able or 
available to give consent, describe the consent process.   
 
[Emergency Consent Process]-Required/Required 
 
[Rescreening]-Required/Required 
Value-Rescreening 
If participants can be rescreened, add the text to state whether the 
participant needs to complete a new consent.  Screen failure and 
rescreening should be clearly defined in the protocol, with cross-
reference to those definitions. 
 
[Consent Requirements for Rescreening]Required/Required 
If participants will be asked to consent to optional exploratory research 
using the remainder of mandatory samples, include text that addresses 
the use of remaining samples for optional exploratory research. 
 
[Additional ICF text for Use of Remaining Samples in Optional 
Exploratory Research] 
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Regulatory, Ethical, and Trial Oversight 
from ToC 
Considerations / Informed Consent Process 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: yes 
Relationship: n/a 
Concept: n/a 
 
Note: This field can contain a text value 
Duplicate field in   
other sections 
584   
Page 310 of 346 
   
585  10.4  Data Protection 
Term (Variable)  Data Protection 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  Include all measures to be taken to comply with the applicable rules on 
protection of personal data and any relevant information on measures to 
be taken in case of a data security breach 
[Data Protection] 
 
Conformance  Optional 
Cardinality   
Relationship content  General Considerations: Regulatory, Ethical, and Trial Oversight 
from ToC 
C  onsiderations / Data Protection 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Data Protection 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Note: This field can contain a text value 
Duplicate field in   
other sections 
586   
Page 311 of 346 
   
587  10.5  Early Site Closure or Trial Termination 
Term (Variable)  Early Site Closure orTrial Termination 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Regulatory, Ethical, and Trial Oversight 
from ToC 
Considerations / Data Protection 
representing the 
 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Note: This field can contain a text value 
Duplicate field in   
other sections 
Duplicate field in   
other sections 
588   
Page 312 of 346 
   
Term (Variable)  Decision Rights for Site Closure and Trial Termination 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Regulatory, Ethical, and Trial Oversight 
from ToC 
Considerations / Data Protection 
representing the 
 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Note: This field can contain a text value 
Duplicate field in   
other sections 
Duplicate field in   
other sections 
589   
Term (Variable)  Criteria for Early Closure 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Regulatory, Ethical, and Trial Oversight 
from ToC 
Considerations / Data Protection 
representing the 
 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Note: This field can contain a text value 
Duplicate field in   
other sections 
Duplicate field in   
other sections 
590   
Page 313 of 346 
   
Term (Variable)  Responsibilities Following Termination or Suspension 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Regulatory, Ethical, and Trial Oversight 
from ToC 
Considerations / Data Protection 
representing the 
 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Note: This field can contain a text value 
Duplicate field in   
other sections 
Duplicate field in   
other sections 
591   
Page 314 of 346 
   
592  11.  General Considerations: Risk Management and Quality Assurance 
Term (Variable)  General Considerations: Risk Management and Quality Assurance 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Risk Management and Quality Assurance 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  General Considerations: Risk Management and Quality Assurance 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
593  11.1  Quality Tolerance Limits 
Term (Variable)  Quality Tolerance Limits 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Risk Management and Quality Assurance 
from ToC 
/Quality by Design and Quality Tolerance Limits 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Quality Tolerance Limits 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
594   
Page 315 of 346 
   
Term (Variable)  Quality Tolerance Limits 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance 
Indicate aspects of the trial design which attend to the principles of 
Quality by Design, such as clear trial objectives, meaningful endpoints, 
and selection of appropriate trial population.  Indicate where Quality 
Tolerance Limits will be predefined, how they will be monitored during 
the trial, and expected discussion in the clinical trial report. 
[QTL] 
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Risk Management and Quality Assurance 
from ToC 
/Quality by Design and Quality Tolerance Limits 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Note: This field can contain a text value 
Duplicate field in   
other sections 
595   
Page 316 of 346 
   
596  11.2  Data Quality Assurance 
Term (Variable)  Data Quality Assurance 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance  Delineate the responsibilities of the Sponsor and Investigator with 
respect to data quality assurance. 
[Sponsor or Designee Responsibilities for Data Quality 
Assurance] 
[Investigator Responsibilities for Data Quality Assurance] 
 
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Risk Management and Quality Assurance /Data 
from ToC 
Quality Assurance 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Data Quality Assurance 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
597   
Page 317 of 346 
   
Term (Variable)  Data Quality Assurance 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance  Delineate the responsibilities of the Sponsor and Investigator with 
respect to data quality assurance. 
[Sponsor or Designee Responsibilities for Data Quality Assurance] 
[Investigator Responsibilities for Data Quality Assurance] 
 
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Risk Management and Quality Assurance /Data 
from ToC 
Quality Assurance 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Data Quality Assurance 
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Note: This field can contain a text value 
Duplicate field in   
other sections 
598   
Page 318 of 346 
   
Term (Variable)  Data Quality Assurance 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Delineate the responsibilities of the Sponsor and Investigator with 
respect to data quality assurance. 
[Sponsor or Designee Responsibilities for Data Quality 
Assurance] 
[Investigator Responsibilities for Data Quality Assurance] 
 
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Risk Management and Quality Assurance /Data 
from ToC 
Quality Assurance 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Note: This field can contain a text value 
Duplicate field in   
other sections 
599   
Page 319 of 346 
   
600  11.3  Source Data 
Term (Variable)  Source Data 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance 
Establish the importance of source data and expectation for traceability 
of transcribed information back to source.  Delineate expectations for 
Investigators and trial monitors.  Define what constitutes source data 
and its origin or provide a reference to the location of these definitions, 
if contained in a separate document, such as a monitoring guideline or 
source data acknowledgement). 
[Source Data Introduction]- Required/Required 
[Investigator Expectations for Source Data]- Required/Required 
[Trial Monitor Expectations for Source Data]- Required/Required 
[Definition of Source Data]- Required/Required 
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Risk Management and Quality Assurance 
from ToC 
/Source Data 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Source Data 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
601   
Page 320 of 346 
   
Term (Variable)  Source Data Introduction 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Procedures for the identification of data to be recorded directly on the 
CRF considered as source data. 
User Guidance 
Establish the importance of source data and expectation for traceability 
of transcribed information back to source.  Delineate expectations for 
Investigators and trial monitors.  Define what constitutes source data 
and its origin or provide a reference to the location of these definitions, 
if contained in a separate document, such as a monitoring guideline or 
source data acknowledgement). 
[Source Data Introduction]- Required/Required 
[Investigator Expectations for Source Data]- Required/Required 
[Trial Monitor Expectations for Source Data]- Required/Required 
[Definition of Source Data]- Required/Required 
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Risk Management and Quality Assurance 
from ToC 
/Source Data 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Note: This field can contain a text value 
Duplicate field in   
other sections 
602   
Page 321 of 346 
   
Term (Variable)  Investigator Expectations for Source Data 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Procedures for the identification of data to be recorded directly on the 
CRF considered as source data. 
User Guidance 
Establish the importance of source data and expectation for traceability 
of transcribed information back to source.  Delineate expectations for 
Investigators and trial monitors.  Define what constitutes source data 
and its origin or provide a reference to the location of these definitions, 
if contained in a separate document, such as a monitoring guideline or 
source data acknowledgement). 
[Source Data Introduction]- Required/Required 
[Investigator Expectations for Source Data]- Required/Required 
[Trial Monitor Expectations for Source Data]- Required/Required 
[Definition of Source Data]- Required/Required 
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Risk Management and Quality Assurance 
from ToC 
/Source Data 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Note: This field can contain a text value 
Duplicate field in   
other sections 
603   
Page 322 of 346 
   
Term (Variable)  Trial Monitor Expectations for Source Data 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Procedures for the identification of data to be recorded directly on the 
CRF considered as source data. 
User Guidance 
Establish the importance of source data and expectation for traceability 
of transcribed information back to source.  Delineate expectations for 
Investigators and trial monitors.  Define what constitutes source data 
and its origin or provide a reference to the location of these definitions, 
if contained in a separate document, such as a monitoring guideline or 
source data acknowledgement). 
[Source Data Introduction]- Required/Required 
[Investigator Expectations for Source Data]- Required/Required 
[Trial Monitor Expectations for Source Data]- Required/Required 
[Definition of Source Data]- Required/Required 
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Risk Management and Quality Assurance 
from ToC 
/Source Data 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Note: This field can contain a text value 
Duplicate field in   
other sections 
604   
Page 323 of 346 
   
Term (Variable)  Definition of Source Data 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Procedures for the identification of data to be recorded directly on the 
CRF considered as source data. 
User Guidance 
Establish the importance of source data and expectation for traceability 
of transcribed information back to source.  Delineate expectations for 
Investigators and trial monitors.  Define what constitutes source data 
and its origin or provide a reference to the location of these definitions, 
if contained in a separate document, such as a monitoring guideline or 
source data acknowledgement). 
[Source Data Introduction]- Required 
[Investigator Expectations for Source Data]- Required 
[Trial Monitor Expectations for Source Data]- Required 
[Definition of Source Data]- Required 
Conformance  Required 
Cardinality   
Relationship content  General Considerations: Risk Management and Quality Assurance 
from ToC 
/Source Data 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Note: This field can contain a text value 
Duplicate field in   
other sections 
605   
Page 324 of 346 
   
606  12.  Appendix: Adverse Events and Serious Adverse Events-Definitions, 
607  Severity, and Causality 
Term (Variable)  Appendix / Appendix 12 Adverse Events and Serious Adverse Events-
Definitions, Severity, and Causality 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Appendix / Appendix 12 Adverse Events and Serious Adverse Events-
from ToC 
Definitions, Severity, and Causality 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Appendix / Appendix 12 Adverse Events and Serious Adverse Events-
Definitions, Severity, and Causality 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
608   
Page 325 of 346 
   
609  12.1  Further Details and Clarifications on the AE Definition 
Term (Variable)  Further Details and Clarifications on the AE Definition 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product and which does not 
necessarily have a causal relationship with this treatment. An adverse 
event (AE) can therefore be any unfavourable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational) 
product, whether or not related to the medicinal (investigational) 
product (see the ICH Guideline for Clinical Safety Data Management: 
Definitions and Standards for Expedited Reporting). 
User Guidance  Specify: 
  The AE definition.  The standard definition is below is from ICH 
E2A Clinical Safety Data Management:  Definitions and Standards for 
Expedited Reporting.  Note that clarifications of events that do and do 
not meet the definition are not standard and may need to be customised 
for the trial. 
  Any relevant regional requirements. 
  Events that meet and do not meet the AE definition. 
  Any trial-specific clarifications. 
Conformance  Required 
Cardinality   
Relationship content  Appendix / Appendix 12 Adverse Events and Serious Adverse Events-
from ToC 
Definitions, Severity, and Causality/Definition of Adverse Event 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Further Details and Clarifications on the AE Definition 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
610   
Page 326 of 346 
   
Term (Variable)  Further Details and Clarifications on the AE Definition 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product and which does not 
necessarily have a causal relationship with this treatment. An adverse 
event (AE) can therefore be any unfavourable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational) 
product, whether or not related to the medicinal (investigational) 
product (see the ICH Guideline for Clinical Safety Data Management: 
Definitions and Standards for Expedited Reporting). 
User Guidance  Specify: 
  The AE definition.  The standard definition is below is from ICH 
E2A Clinical Safety Data Management:  Definitions and Standards for 
Expedited Reporting.  Note that clarifications of events that do and do 
not meet the definition are not standard and may need to be customised 
for the trial. 
  Any relevant regional requirements. 
  Events that meet and do not meet the AE definition. 
  Any trial-specific clarifications. 
Conformance  Required 
Cardinality   
Relationship content  Appendix / Appendix 12 Adverse Events and Serious Adverse Events-
from ToC 
Definitions, Severity, and Causality/Definition of Adverse Event 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
611   
Page 327 of 346 
   
612  12.2  Further Details and Clarifications on the SAE Definition 
Term (Variable)  Further Details and Clarifications on the SAE Definition 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section heading 
User Guidance  Specify: 
  The SAE definition.  The standard definition is in ICH E2A. 
  Any relevant regional requirements. 
  Events that meet and do not meet the SAE definition. 
  Any trial-specific clarifications.  
[Further Details and Clarifications on the SAE Definition] 
 
Conformance  Required 
Cardinality   
Relationship content  Appendix / Appendix 12 Adverse Events and Serious Adverse Events-
from ToC 
Definitions, Severity, and Causality/Further Details and Clarifications on 
representing the 
the SAE Definition 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Further Details and Clarifications on the SAE Definition 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
613   
Page 328 of 346 
   
Term (Variable)  Further Details and Clarifications on the SAE Definition 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  A SAE is any untoward medical occurrence that, at any dose: 
a.  Results in death 
b.  Is life-threatening 
c.  Requires hospitalisation or prolongation of existing hospitalisation 
d.  Results in persistent disability or incapacity 
e.  Is a congenital anomaly or birth defect 
f.  Is another important medical event that may not result in death, 
be life-threatening, or require hospitalisation, but is considered serious 
when, based upon appropriate medical judgment, it may jeopardise the 
participant and may require medical or surgical intervention to prevent 
one of the outcomes listed above. 
User Guidance  Specify: 
  The SAE definition.  The standard definition is in ICH E2A. 
  Any relevant regional requirements. 
  Events that meet and do not meet the SAE definition. 
  Any trial-specific clarifications.  
[Further Details and Clarifications on the SAE Definition] 
 
Conformance  Required 
Cardinality   
Relationship content  Appendix / Appendix 12 Adverse Events and Serious Adverse Events-
from ToC 
Definitions, Severity, and Causality/Further Details and Clarifications on 
representing the 
the SAE Definition 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Page 329 of 346 
   
Value  A SAE is any untoward medical occurrence that, at any dose: 
  Results in death 
  Is life-threatening 
a.  Requires hospitalisation or prolongation of existing hospitalisation 
b.  Results in persistent disability or incapacity 
c.  Is a congenital anomaly or birth defect 
d.  Is another important medical event that may not result in death, 
be life-threatening, or require hospitalisation, but is considered serious 
when, based upon appropriate medical judgment, it may jeopardise the 
participant and may require medical or surgical intervention to prevent 
one of the outcomes listed above. 
Examples include intensive treatment in an emergency room or at home 
for allergic bronchospasm, blood dyscrasias or convulsions that do not 
result in hospitalisation, or development of drug dependency or drug 
abuse. 
 
Clarifications of the SAE definition: 
1)  An event is life-threatening if its occurrence places the participant 
at immediate risk of death. It does not include an event that, had it 
occurred in a more severe form, might have caused death. 
2)  An event is serious if it is not appropriate to administer treatment 
in a physicians office or an outpatient setting, and it requires 
hospitalisation. An event is also serious if it prolongs hospitalisation. 
When in doubt as to whether hospitalisation occurred or was 
necessary, the event is considered serious. 
3)  Hospitalisation for elective treatment of a pre-existing condition 
that did not worsen from baseline is not an AE. 
4)  Disability is a substantial or significant disruption of a persons 
ability to conduct normal life functions. 
5)  The investigator may deem as an SAE any other important 
medical event that did not result in any of the outcomes listed in this 
section due to medical or surgical intervention 
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
614   
Page 330 of 346 
   
615  12.3  Severity 
Term (Variable)  Severity 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Appendix / Appendix 12 Adverse Events and Serious Adverse Events-
from ToC 
Definitions, Severity, and Causality/Severity 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Severity 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a  
Duplicate field in   
other sections 
616   
Term (Variable)  Severity  
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance  Specify the rating categories/scale to be used in the trial to assess 
severity.  Example scales are in [document name]. Considerations for 
assessing severity are discussed in ICH E2A. 
[Severity] 
Conformance  Required 
Cardinality   
Relationship content  Appendix / Appendix 12 Adverse Events and Serious Adverse Events-
from ToC 
Definitions, Severity, and Causality/Severity 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
617   
Page 331 of 346 
   
618  12.4  Causality 
Term (Variable)  Causality 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Appendix / Appendix 12 Adverse Events and Serious Adverse Events-
from ToC 
Definitions, Severity, and Causality/Severity 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Causality 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
619   
Page 332 of 346 
   
Term (Variable)  Causality 
Data Type  Text 
Topic, Value or  D 
Header 
Definition  Defines the relationship of an AE to a trial intervention 
User Guidance  Specify the causality categories/scale that the investigator will use for 
his/her assessment.  Considerations for assessing causality are 
discussed in ICH E2A. Evaluation of relatedness must consider 
temporality and biologic plausibility as well as etiologies such as natural 
history of the underlying disease, concurrent illness, concomitant 
therapy, trial-related procedures, accidents, and other external factors.  
In a clinical trial, the trial intervention must always be suspect. The 
Investigators assessment of an AE's relationship to trial intervention is 
not a factor in determining what is or is not reported in the trial. If there 
is any doubt as to whether a clinical observation is an AE, the event 
should be reported. 
[Causality] 
Conformance  Required 
Cardinality   
Relationship content  Appendix / Appendix 12 Adverse Events and Serious Adverse Events-
from ToC 
Definitions, Severity, and Causality/Severity 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
620   
Page 333 of 346 
   
621  13.  Appendix: Definitions and Supporting Operational Details 
Term (Variable)  Appendix: Definitions and Supporting Operational Details 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Appendix: Definitions and Supporting Operational Details 
from ToC 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Appendix: Definitions and Supporting Operational Details 
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
622  13.1  Contraception and Pregnancy Testing 
Term (Variable)  Contraception and Pregnancy Testing 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Appendix 13: Definitions and Supporting Operational Details/ 
from ToC 
Contraception and Pregnancy Testing 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Contraception and Pregnancy Testing 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
623  13.1.1  Definitions Related to Childbearing Potential 
Page 334 of 346 
   
Term (Variable)  Definitions for Contraception and Pregnancy Testing 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance   
Conformance  Required 
Cardinality   
Relationship content  Appendix: Definitions and Supporting Operational Details/ Contraception 
from ToC 
and Pregnancy Testing/Definitions for Contraception and Pregnancy 
representing the 
Testing 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
624  13.1.2  Contraception 
Term (Variable)  Contraception 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance 
Optional section to specify the:  
  Contraceptive methods required   
  Duration of use 
[Contraception] 
 
Conformance  Required 
Cardinality   
Relationship content  Appendix 13: Definitions and Supporting Operational Details/ 
from ToC 
Contraception and Pregnancy Testing/Contraception 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Contraception 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
625   
Page 335 of 346 
   
Term (Variable)  Contraception 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance 
Optional section to specify the:  
  Contraceptive methods required   
  Duration of use 
[Contraception] 
 
Conformance  Required 
Cardinality   
Relationship content  Appendix: Definitions and Supporting Operational Details/ Contraception 
from ToC 
and Pregnancy Testing/Contraception 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
626   
Page 336 of 346 
   
627  13.1.3  Pregnancy Testing 
Term (Variable)  Pregnancy Testing 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance 
Optional section to specify pregnancy testing requirements. 
[Pregnancy Testing] 
 
 
Conformance  Required 
Cardinality   
Relationship content  Appendix: Definitions and Supporting Operational Details/ Contraception 
from ToC 
and Pregnancy Testing/Pregnancy Testing 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Pregnancy Testing 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
628   
Page 337 of 346 
   
Term (Variable)  Pregnancy Testing 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance 
Optional section to specify pregnancy testing requirements. 
[Pregnancy Testing] 
 
 
Conformance  Required 
Cardinality   
Relationship content  Appendix: Definitions and Supporting Operational Details/ Contraception 
from ToC 
and Pregnancy Testing/Pregnancy Testing 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
629   
Page 338 of 346 
   
630  13.2  Clinical Laboratory Tests 
Term (Variable)  Clinical Laboratory Tests 
Data Type  Text 
Topic, Value or  H 
Header 
Definition  Section Heading 
User Guidance 
Provide additional information, if needed, about clinical laboratory tests, 
such as  
  whether they will be performed by a central or local laboratory (if 
important to distinguish)  
  specific analytes or parameters included in a panel  
  equations and references for locally calculated labs  
  acceptability of additional tests deemed necessary by the 
Investigator or local regulations 
  instructions for situations in which central laboratory results are 
not available in time for trial intervention and/or response 
evaluation, or in the event of a severe disruption (for example, a 
pandemic or natural disaster) 
  treatment algorithms for results out of normal range. 
A tabular presentation for such information is common. 
[Clinical Laboratory Tests] 
 
Conformance  Required 
Cardinality   
Relationship content  Appendix: Definitions and Supporting Operational Details/Clinical 
from ToC 
Laboratory Tests 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Clinical Laboratory Tests 
Business rules  Value Allowed: Yes 
Relationship: n/a 
Concept: n/a 
Duplicate field in  Repeat for lab values 
other sections 
631   
Page 339 of 346 
   
Term (Variable)  Clinical Laboratory Tests 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance 
Provide additional information, if needed, about clinical laboratory tests, 
such as  
  whether they will be performed by a central or local laboratory (if 
important to distinguish)  
  specific analytes or parameters included in a panel  
  equations and references for locally calculated labs  
  acceptability of additional tests deemed necessary by the 
Investigator or local regulations 
  instructions for situations in which central laboratory results are 
not available in time for trial intervention and/or response 
evaluation, or in the event of a severe disruption (for example, a 
pandemic or natural disaster) 
  treatment algorithms for results out of normal range. 
A tabular presentation for such information is common. 
[Clinical Laboratory Tests] 
 
Conformance  Required/Repeatable (for lab values) 
Cardinality   
Relationship content  Appendix: Definitions and Supporting Operational Details/Clinical 
from ToC 
Laboratory Test 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
632   
Page 340 of 346 
   
633  13.3  Country/Region-Specific Differences 
Term (Variable)  Country-Specific Differences 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance 
Although global clinical trial practices are increasingly harmonised, some 
country- and region-specific differences in requirements do exist (for 
example, document retention periods, contraception requirements).  
Where differences in requirements cannot be reconciled, sponsors should 
explain how they will document and communicate country-specific 
differences (for example, by country-specific amendments or addenda).   
An alternative to country- or region-specific amendments is to list the 
specific differences by country or countries in this section, including a 
reference to the relevant section of the protocol where the differing 
requirement applies.   
[Country-specific Differences] 
Conformance  Required 
Cardinality   
Relationship content  Appendix: Definitions and Supporting Operational Details/Country-
from ToC 
Specific Differences 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Country-Specific Differences 
Business rules  Value Allowed: Yes 
Relationship: 0 to many 
Concept: n/a 
Duplicate field in   
other sections 
634   
Page 341 of 346 
   
Term (Variable)  Country 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance 
Although global clinical trial practices are increasingly harmonised, some 
country- and region-specific differences in requirements do exist (for 
example, document retention periods, contraception requirements).  
Where differences in requirements cannot be reconciled, sponsors should 
explain how they will document and communicate country-specific 
differences (for example, by country-specific amendments or addenda).   
An alternative to country- or region-specific amendments is to list the 
specific differences by country or countries in this section, including a 
reference to the relevant section of the protocol where the differing 
requirement applies.   
[Country] 
Conformance  Required/Repeatable 
Cardinality   
Relationship content  Appendix: Definitions and Supporting Operational Details/Country-
from ToC 
Specific Differences/Country 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Country 
Business rules  Value Allowed: n/a 
Relationship: 0 to many 
Concept: n/a 
Duplicate field in   
other sections 
635   
Page 342 of 346 
   
Term (Variable)  Header of Protocol Section to be Changed for the Country 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance 
Although global clinical trial practices are increasingly harmonised, some 
country- and region-specific differences in requirements do exist (for 
example, document retention periods, contraception requirements).  
Where differences in requirements cannot be reconciled, sponsors should 
explain how they will document and communicate country-specific 
differences (for example, by country-specific amendments or addenda).   
An alternative to country- or region-specific amendments is to list the 
specific differences by country or countries in this section, including a 
reference to the relevant section of the protocol where the differing 
requirement applies.   
[Header of Protocol Section to be Changed for the Country] 
Conformance  Required/Repeatable 
Cardinality   
Relationship content  Appendix: Definitions and Supporting Operational Details/Country-
from ToC 
Specific Differences/Country/Header of Protocol Section to be Changed 
representing the 
for the Country 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Header of Protocol Section to be Changed for the Country 
Business rules  Value Allowed: n/a 
Relationship: 0 to many 
Concept: n/a 
Duplicate field in   
other sections 
636   
Page 343 of 346 
   
Term (Variable)  [Change-depends on Section] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance 
Although global clinical trial practices are increasingly harmonised, some 
country- and region-specific differences in requirements do exist (for 
example, document retention periods, contraception requirements).  
Where differences in requirements cannot be reconciled, sponsors should 
explain how they will document and communicate country-specific 
differences (for example, by country-specific amendments or addenda).   
An alternative to country- or region-specific amendments is to list the 
specific differences by country or countries in this section, including a 
reference to the relevant section of the protocol where the differing 
requirement applies.   
[Header of Protocol Section to be Changed for the Country] 
 
Conformance  Optional (follows original section) 
Cardinality   
Relationship content  Appendix: Definitions and Supporting Operational Details/Country-
from ToC 
Specific Differences/Country/Header of Protocol Section to be Changed 
representing the 
for the Country 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: 0 to many 
Concept: n/a 
Duplicate field in   
other sections 
637   
Page 344 of 346 
   
638  13.4   Prior Protocol Amendments 
Term (Variable)  Prior Protocol Amendments 
Data Type  Text 
Topic, Value or  H 
Header 
Definition   
User Guidance 
Choose the appropriate text. 
{This protocol has not been amended.} 
or 
{The Protocol Amendment Summary of Changes for the current 
amendment is located directly before the Table of Contents.  Details of 
prior amendments are presented below, beginning with the most 
recent}. 
See the instructions in the Protocol Amendment Summary of Changes 
located before the Table of Contents. Move all Protocol Amendment 
Summaries of Changes for previous amendments to this section in 
reverse chronological order (most recent first). 
Amendment {amendment number}: ({date}) 
{Amendment details from this amendment} 
Add additional amendments/details as protocol amendments 
accrue. 
Amendment {amendment number}: ({date}) 
{Amendment details from this amendment} 
Conformance  Required 
Cardinality   
Relationship content  Appendix: Definitions and Supporting Operational Details/Prior Protocol 
from ToC 
Amendments 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value  Prior Protocol Amendments 
Business rules  Value Allowed: Yes 
Relationship: 0 to many 
Concept: n/a 
Duplicate field in   
other sections 
639   
Page 345 of 346 
   
Term (Variable)  [Statement] 
Data Type  List 
Topic, Value or  D 
Header 
Definition   
User Guidance 
 
Conformance  Required 
Cardinality   
Relationship content  Appendix: Definitions and Supporting Operational Details/Prior Protocol 
from ToC 
Amendments/Statement 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: n/a 
Concept: n/a 
Duplicate field in   
other sections 
640   
Term (Variable)  [Protocol Amendment Summary] 
Data Type  Text 
Topic, Value or  D 
Header 
Definition   
User Guidance 
 
Conformance  Required/Repeated 
Cardinality   
Relationship content  Appendix: Definitions and Supporting Operational Details/Prior Protocol 
from ToC 
Amendments/Protocol Amendment Summary 
representing the 
protocol hierarchy 
Relationship   
(reference to high 
level conceptual 
model) 
Value   
Business rules  Value Allowed: n/a 
Relationship: 104 to 144 from preceding amendment list all in most 
recent order 
Concept: n/a 
Duplicate field in   
other sections 
641   
Page 346 of 346