Bioresearch Monitoring Technical Conformance Guide

Administrative guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

Contains Nonbinding Recommendations
BIORESEARCH MONITORING
TECHNICAL CONFORMANCE GUIDE
Technical Specifications Document
This Document is Referenced by the Following Draft Guidance Document:
Standardized Format for Electronic Submission of NDA and BLA Content for the
Planning of Bioresearch Monitoring (BIMO) Inspections for CDER Submissions
For questions regarding this technical specifications document, contact CDER-BIMO-
NDA-BLA-request@fda.hhs.gov.
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
September 2024

Contains Nonbinding Recommendations
BIORESEARCH MONITORING
TECHNICAL CONFORMANCE GUIDE
September 2024

Contains Nonbinding Recommendations
Revision History
Date 	Version 	Summary of Changes
12/28/2017 	1.0 	Original Version
07/23/2020 	2.0 	1. 	Corrected footnote hyperlinks
2. 	Edited variable names in
examples and tables to
maintain consistency across
document
3. 	Clarified document, listings,
and data requests
4. 	Deleted request for SITEFFE
and SITEFFS variables in
clinsite.xpt
5. 	Added COHORT variable
6. 	Revised PROTVIOL variable
to IMPDEV and NOIMPDEV
variables
7. 	Provided additional
instructions for placement of
files per eCTD format
08/11/2022 	3.0 	1. 	Rename BIMO Review Guide
to BIMO Data Review Guide.
2. 	Renamed TRTEFFR to
TRTEFFR1
3. 	Added EFFPOP, TRTEFFR2,
and CENSOR2 Variables
4. 	Deleted request for TRTEFFS
5. 	Change instructions for use of
ISO codes to use of
Geopolitical Entities, Names
and Codes (GENC) codelist.
6. 	Minor editorial changes.
09/03/2024 	3.1 	1. 	Updated introductory
language

Contains Nonbinding Recommendations
TABLE OF CONTENTS
I. 	CLINICAL STUDY-LEVEL INFORMATION 	1
A. 	COMPREHENSIVE AND R EADILY LOCATED L IST OF A LL CLINICAL S ITES ......................................................... 1
B. 	TABLE LISTING A LL ENTITIES TO W HOM S PONSOR H AS C ONTRACTED C LINICAL S TUDY-R ELATED
A CTIVITIES ....................................................................................................................................................... 1
C. 	P ROTOCOL, P ROTOCOL A MENDMENTS , AND A NNOTATED C ASE R EPORT F ORM ............................................... 2
II. 	SUBJECT-LEVEL DATA LINE LISTINGS BY CLINICAL SITE 	2
A. 	O RGANIZATION OF THE S UBJECT-L EVEL D ATA LINE L ISTINGS ........................................................................ 2
B. 	S ITE-S PECIFIC LISTINGS F ORMAT ..................................................................................................................... 4
III. 	SUMMARY-LEVEL CLINICAL SITE DATASET 	5
A. 	O RGANIZATION OF THE S ITE-L EVEL D ATASET ................................................................................................. 5
B. 	V ARIABLES AND V ARIABLE N AMES FOR S ITE -S PECIFIC EFFICACY RESULTS .................................................... 5
C. 	CREATING THE D ATA F ILE (T EMPLATE AND S TRUCTURE) ................................................................................ 7
IV. 	SUBMITTING BIMO CLINICAL DATA IN THE ECTD FORMAT 	7
A. 	S TUDY TAGGING F ILE ....................................................................................................................................... 7
B. 	ECTD F OLDER S TRUCTURE FOR CLINICAL S TUDY-L EVEL I NFORMATION AND S UBJECT-L EVEL LINE LISTINGS
BY CLINICAL S ITE ............................................................................................................................................. 8
C. 	ECTD F OLDER S TRUCTURE FOR S UMMARY-L EVEL C LINICAL S ITE D ATASET .................................................. 8
D. 	F ILE F ORMAT .................................................................................................................................................... 9
E. 	LEAF TITLES ..................................................................................................................................................... 9
F. 	S UBMISSION ...................................................................................................................................................... 9
APPENDIX 1: CLINICAL STUDY-LEVEL INFORMATION 	11
APPENDIX 2: FORMATTING SUBJECT-LEVEL DATA LINE LISTINGS BY CLINICAL SITE 	12
APPENDIX 3: CLINICAL SITE DATA ELEMENTS SUMMARY LISTING 	14
APPENDIX 4: EXAMPLES 	19

Contains Nonbinding Recommendations
1
Bioresearch Monitoring Technical Conformance Guide	1
2
This technical conformance guide represents the current thinking of the Food and Drug	3
Administration (FDA or Agency) on this topic. It does not establish any rights for any person	4
and is not binding on FDA or the public. You can use an alternative approach if it satisfies the	5
requirements of the applicable statutes and regulations. If you want to discuss an alternative	6
approach, contact the FDA staff responsible for this technical conformance guide. If you cannot	7
identify the appropriate FDA staff, send an email to cder-edata@fda.hhs.gov or	8
cber.cdisc@fda.hhs.gov.	9
10
This Bioresearch Monitoring Technical Conformance Guide (Guide) provides current FDA	11
specifications, recommendations, and general considerations for preparing and submitting	12
Clinical Study-Level Information, Subject-Level Data Line Listings by Clinical Site, and a	13
Summary-Level Clinical Site Dataset that are used by the Center for Drug Evaluation and	14
Research (CDER) for planning of Bioresearch Monitoring (BIMO) inspections in electronic	15
format for new drug applications (NDAs), biologics license applications (BLAs), and NDA or	16
BLA supplemental applications containing clinical data that are regulated by CDER.1 It also	17
applies when these data and information are submitted under certain investigational new drug	18
applications2 (INDs) in advance of a planned NDA, BLA, or supplemental submission.	19
20
21
I. 	CLINICAL STUDY-LEVEL INFORMATION	22
23
A. 	Comprehensive and Readily Located List of All Clinical Sites	24
25
The recommended format for the portable document format (PDF) of the comprehensive and	26
readily located list(s) of all clinical sites that participated in clinical studies for each major (i.e.,	27
pivotal) study is provided in Appendix 1 of this Guide.	28
29
B. 	Table Listing All Entities To Whom Sponsor Has Contracted Clinical Study-	30
Related Activities	31
32
In the table(s) listing entities to whom the sponsor has contracted clinical study-related activities,	33
which are provided in a PDF for each pivotal study, the applicant should identify the location of	34
study-related documents for each study and whether they are sponsor- or Contract Research	35
Organization-generated. For example, these documents may include, but are not limited to,	36
monitoring plans and reports, training records, and data analysis plans (e.g., items that some	37
applicants organize in a Trial Master File). When the location of study-related documents has	38
not been finalized, the applicant should provide contact information (i.e., phone number and	39
1 We update technical conformance guides periodically. For the most recent version of this Guide, check the FDA
guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents.
2 See FDA guidance for industry Providing Regulatory Submissions in Electronic Format – Certain Human
Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications (February 2020).
We update guidances periodically. For the most recent version of a guidance, check the FDA guidance web page at
https://www.fda.gov/regulatory-information/search-fda-guidance-documents.

Contains Nonbinding Recommendations
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email address) for the individual(s) who can provide updated location information upon request.	40
This information ensures that when CDER issues an inspection assignment for the application,	41
the inspection is of the most responsible entity for a given regulatory responsibility, and that the	42
inspection assignment is issued for the location where records are present for review.	43
44
C. 	Protocol, Protocol Amendments, and Annotated Case Report Form	45
46
The protocol and protocol amendments, with associated versions of the case report form, and the	47
final version of the annotated case report form (case report form containing Clinical Data	48
Interchange Standards Consortium and Study Data Tabulation Model (SDTM) annotations) are	49
generally included in Appendix 163 of the Clinical Study Report or in the datasets folder for each	50
study. When these items are included in an appendix to the Clinical Study Report or the dataset	51
folder for the study, there is no need to resubmit them. If the applicant is submitting a BIMO	52
Data Reviewer’s Guide,4 the applicant should note that these items are present in an appendix of	53
the Clinical Study Report or the dataset folder where they are placed.	54
55
These items are included in the background materials provided to the Office of Regulatory	56
Affairs for BIMO inspections; it is important to provide all versions of these documents so that	57
the field investigator performing the inspection can reference the correct versions of protocols	58
and case report forms in place at the time of the conduct of specific study procedures.	59
60
61
II. 	SUBJECT-LEVEL DATA LINE LISTINGS BY CLINICAL SITE	62
63
A. 	Organization of the Subject-Level Data Line Listings	64
65
Examples of the formatting for the PDF of subject-level data line listings provided for each	66
major (i.e., pivotal) study used to support safety and efficacy in the application, including studies	67
with different treatment indications, are provided in Appendix 2 of this Guide. If the sponsor	68
believes alternative listings or formats are preferable for its submission, proposed alternatives	69
should be discussed with the Office of Scientific Investigations in advance of the application	70
submission—for example, before or during pre-NDA or pre-BLA meetings.	71
72
For clinical investigator sites involved in multiple studies in support of an application, the	73
subject listings should be provided independently for each study within the study-associated	74
PDF.	75
76
Subject-level data line listings, by clinical site, should include consented subjects, treatment	77
assignment, discontinuations, study population, inclusion and exclusion criteria, adverse events,	78
protocol deviations, efficacy endpoints, concomitant medications, and safety monitoring, as	79
further described below.	80
81
3 See ICH guidance for industry E3 Structure and Content of Clinical Study Reports (July 1996).
4 A specific template for a BIMO Data Reviewer’s Guide is not specified. However, an example can be found at
https://advance.phuse.global/display/WEL/Deliverables.

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1. 	Consented Subjects	82
83
This by-subject, by-clinical site listing includes all subjects that consented to enroll in the study.	84
Consented subjects that were screen failures should also be included. For subjects that consented	85
but were not randomized to treatment or did not receive investigational product, the specific	86
reason they were not randomized or treated should be included in this listing.	87
88
2. 	Treatment Assignment	89
90
This by-subject, by-clinical site listing includes the treatment assignment to which the subject	91
was randomized. If a subject mistakenly received treatment different from the subject’s assigned	92
treatment for any duration of time, the actual treatment received should also be included.	93
94
3. 	Discontinuations	95
96
This by-subject, by-clinical site listing includes:	97
98
• 	All subjects that discontinued during run-in period (if applicable)	99
• 	All subjects that discontinued from study treatment	100
• 	All subjects that discontinued from the study completely	101
102
For each subject, the date of and reason for discontinuation should be provided.	103
104
4. 	Study Population	105
106
This by-subject, by-clinical site listing identifies the protocol-defined study population in which	107
each subject was analyzed (e.g., intent-to-treat, safety, per protocol). For subjects that did not	108
meet criteria for inclusion in the per-protocol population, the reason they were excluded from the	109
per-protocol population should be provided.	110
111
5. 	Inclusion and Exclusion Criteria	112
113
This by-subject, by-clinical site listing should display whether each subject met each inclusion	114
and exclusion criterion defined in the protocol.	115
116
6. 	Adverse Events	117
118
This by-subject, by-clinical site listing should include all adverse events (i.e., nonserious adverse	119
events and serious adverse events, including deaths), date of occurrence and time if collected,	120
treatment(s) administered, severity, whether considered serious by the clinical investigator,	121
whether considered serious by the sponsor, action taken, whether the event led to discontinuation	122
of study therapy, and outcome/date of resolution.	123
124
7. 	Protocol Deviations	125
126

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This by-subject, by-clinical site listing should include all protocol deviations. The listing should	127
include a description of the deviation and identify whether the sponsor considered the deviation	128
to be an important or non-important protocol deviation.5	
129
130
8. 	Efficacy Endpoints	131
132
This by-subject, by-clinical site listing(s) should contain primary and key secondary efficacy	133
parameters or events. For derived or calculated endpoints, the raw data points used to generate	134
the derived or calculated endpoint should be provided. For example, when efficacy endpoints	135
are assessed based on a laboratory, imaging, components of a clinical outcome assessment(s), or	136
other study procedures, the by-subject, by-clinical site listing should include all testing results	137
that contribute to the derived efficacy endpoint. When efficacy endpoints are collected as	138
clinical events, a by-subject, by-clinical site listing should be provided that includes clinical	139
event, date of event, and when adjudicated, the date of adjudication and the outcome of the	140
adjudication process.	141
142
9. 	Concomitant Medications	143
144
This by-subject, by-clinical site listing should contain all concomitant medications as specified	145
by the protocol. The date started, date stopped, dose, route of administration, and reason for	146
administration should be included.	147
148
10. 	Safety Monitoring	149
150
This by-subject, by-clinical site listing(s) should contain results of tests (e.g., laboratory,	151
electrocardiogram) performed for safety monitoring as defined in the protocol. When safety	152
endpoints are collected as clinical events, a by-subject, by-clinical site listing should be provided	153
that includes clinical event, date of event, and when adjudicated, the outcome of the adjudication	154
process.	155
156
B. 	Site-Specific Listings Format	157
158
The specified data line listings are anticipated to fit reporting requirements for most applications.	159
If a sponsor believes additional listings are needed to permit FDA to verify key study data during	160
inspections, additional listings should be included. If the size of the PDF file exceeds 500	161
megabytes, it should be split into smaller components.6	
162
163
Although listings are currently requested in PDF format, CDER is in the process of developing	164
tools to extract site-specific listings, needed for inspectional purposes, from submitted Clinical	165
Data Interchange Standards Consortium, SDTM, and Analysis Data Model (ADaM) datasets and	166
intends to make those tools available in the future. FDA intends to update these technical	167
5 See ICH guidance for industry E3 Structure and Content of Clinical Study Reports — Questions and Answers (R1)
(January 2013).
6 See ICH guideline Specification for Submission Formats for eCTD v1.3 (June 2021) at
https://www.ich.org/page/ich-m8-specification-submission-formats-ectd.

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specifications to include details for the submission of SDTM and ADaM datasets, including	168
controlled terminology standards. In anticipation of the development of CDER tools for	169
extraction of by-site, by-subject data listings, sponsors should ensure that they are prepared to	170
submit clinical study data using standards specified in the Data Standards Catalog.7	
171
172
173
III. 	SUMMARY-LEVEL CLINICAL SITE DATASET	174
175
A. 	Organization of the Site-Level Dataset	176
177
A single summary-level clinical site dataset that contains data from all major (i.e., pivotal)	178
studies used to support safety and efficacy in the application, including studies with different	179
treatment indications, should be provided.	180
181
For each major (i.e., pivotal) study used to support safety and efficacy, data by clinical site and	182
treatment arm for the safety population (SAFPOP) and primary efficacy population (EFFPOP)	183
should be provided.	184
185
For clinical investigator sites involved in multiple studies in support of an application, the site	186
data should be reported independently for each study within the dataset.	187
188
B. 	Variables and Variable Names for Site-Specific Efficacy Results	189
190
For each study and investigator site, it is critical to submit the following variables associated	191
with efficacy and their variable names:	192
• 	Safety Population (SAFPOP) — Total number of subjects in safety population at a given	193
site by treatment arm. When a subject has transferred from one site to another, the	194
applicant should handle reporting of such subjects consistently across sites and include in	195
the define file, or the BIMO Data Review Guide when one is provided, the reporting	196
convention used.	197
• 	Primary Efficacy Population (EFFPOP) — Total number of subjects in the primary efficacy	198
population, as defined in the clinical study report, at a given site by treatment arm to support	199
the proposed indication in the application. The efficacy population used should be identified	200
in the define file provided for the clinsite.xpt (e.g., Full Analysis Set, Per Protocol, Intent to	201
Treat, Modified Intent to Treat).	202
• 	Treatment Efficacy Result One (TRTEFFR1) — The summary statistic for each primary	203
efficacy endpoint, by treatment arm at a site, based subjects in the SAFPOP. Values reported	204
in TRTEFFR1 generally reflect simple summary statistics for the primary efficacy	205
endpoint(s). The method used for deriving the TRTEFFR1, including a description of which	206
analysis datasets and associated variables are used to derive the TRTEFFR1, should be	207
described in the define file provided with the clinsite.xpt (see discussion below for examples	208
of summary statistics according to different types of efficacy endpoints).	209
7 Available at http://www.fda.gov/forindustry/datastandards/studydatastandards/default.htm.

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• 	Treatment Efficacy Result Two (TRTEFFR2) —The summary statistic for each primary	210
efficacy endpoint, by treatment arm at a site, based subjects in the EFFPOP. Values reported	211
in TRTEFFR2 generally reflect simple summary statistics for the primary efficacy	212
endpoint(s). The method used for deriving the TRTEFFR2, including a description of which	213
analysis datasets and associated variables are used to derive the TRTEFFR2, should be	214
described in the define file provided with the clinsite.xpt (see discussion below for examples	215
of summary statistics according to different types of efficacy endpoints).	216
• 	Endpoint (ENDPOINT) — A plain-text label that describes the primary endpoint as	217
described in the data definition file data dictionary included with each application.	218
• 	Treatment Arm (ARM) — A plain-text label for the treatment arm that is used in the Clinical	219
Study Report.	220
In addition, for studies whose primary endpoint is a time-to-event endpoint, it is critical to	221
include the following data element:	222
• 	Censored Observations (CENSOR1 and CENSOR2) — The number of censored	223
observations for the given site and by treatment arm for the SAFPOP and EFFPOP,	224
respectively.	225
If a study does not contain a time-to-event endpoint, this data element should be recorded as a	226
missing value (if not applicable, leave blank in clinsite.xpt).	227
228
To accommodate the variety of endpoint types that can be used in analyses, it is critical that the	229
following endpoint type definitions be referenced, and summaries be provided when tabulating	230
the site-specific summary statistic by treatment arm (for TRTEFFR1 and TRTEFFR2):	231
• 	Discrete Endpoints — Endpoints based on efficacy observations that can take on a discrete	232
number of values (e.g., binary, categorical). Summarize discrete endpoints by an event	233
frequency (i.e., number of events), proportion of patients with an event, proportion of	234
patients responding to treatment, or similar method at the site for the given treatment.	235
• 	Continuous Endpoints — Endpoints based on efficacy observations that can take on an	236
infinite number of values. Summarize continuous endpoints by the mean, median, or other	237
distributional quantile of the observations at the site for the given treatment.	238
• 	Time-to-Event Endpoints — Endpoints where the time to occurrence of an event is the	239
primary efficacy measurement. Summarize time-to-event endpoints by two data elements:	240
the number of events that occurred (TRTEFFR1 and TRTEFFR2) and the number of	241
censored observations (CENSOR1 and CENSOR2).	242
• 	Other — If the primary efficacy endpoint cannot be summarized in terms of the previous	243
guidelines, a single value or multiple values with precisely defined variable interpretations	244
should be submitted as part of the dataset.	245
In all cases, the endpoint description provided in the ENDPOINT plain-text label should be	246
expressed clearly to interpret the value provided in the TRTEFFR1 and TRTEFFR2 variables.	247
248

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When more than one primary efficacy endpoint exists, additional rows should be added to the	249
dataset to report additional ENDPOINT, Primary Endpoint Type (ENDPTYPE), TRTEFFR1,	250
and TRTEFFR2 values by arm for each site.	251
252
It is anticipated that efficacy data for all subjects included in the SAFPOP and EFFPOP variables	253
will be included in TRTEFFR1 and TRTEFFR2 variables reported, respectively. If efficacy data	254
is not available for all subjects reported in the SAFPOP or EFFPOP variables, then efficacy data	255
for these subjects should be reported as specified in the study Data Analysis Plan, and the	256
method used for calculation of efficacy variables should be described in the data define table	257
provided with the clinsite.xpt file.	258
259
The summary-level clinical site dataset should be accompanied by a data definition file. The	260
contents of the define file for a dataset and fictional examples are presented in Appendix 3 and	261
Appendix 4 of this Guide.	262
263
C. 	Creating the Data File (Template and Structure)	264
265
A sample summary-level clinical site data submission using the variables identified in Appendix	266
3 of this Guide is provided in Appendix 4.	267
268
269
IV. 	SUBMITTING BIMO CLINICAL DATA IN THE eCTD FORMAT	270
271
Clinical study-level information, subject-level data line listings by clinical site, and the	272
summary-level clinical site dataset submitted with an application, in Electronic Common	273
Document (eCTD) format, should be placed in eCTD Module 5 (M5) — Clinical Study Reports,	274
using the following conventions:	275
A. 	Study Tagging File	276
277
Construct a BIMO study tagging file (STF) and place it in eCTD Module 5.3.5.4, “Other Study	278
reports and related information.” The study identifier (ID) for this STF is “BIMO.” Files	279
described in section III (e.g., Description of Clinical Study-Level Information, Subject-Level	280
Data Line Listings by Clinical Site, and Summary-Level Clinical Site Dataset) of the draft	281
guidance Standardized Format for Electronic Submission of NDA and BLA Content for the	282
Planning of Bioresearch Monitoring (BIMO) Inspections for CDER Submissions (February	283
2018) are linked to this BIMO STF using file tags as indicated below.8 Leaf titles for these data	284
are named “BIMO [list study ID, followed by brief description of file being submitted].”	285
286
Table 1: STF File Tags	287
Requested
Item STF File Tag 	Used For Required
File Formats
III.A.1-2 	data-listing-dataset General clinical study-
level information .pdf
8 When final, this guidance will represent the FDA’s current thinking on this topic.

Contains Nonbinding Recommendations
8
Requested
Item STF File Tag 	Used For Required
File Formats
III.A.3 	Protocol-or-amendment Protocol and Protocol
Amendments, by study .pdf
III.A.3 	annotated-crf Sample annotated case
report form, by study .pdf
III.B 	data-listing-dataset Data listings, by study
(Line listings, by site) .pdf
III.C 	data-listing-dataset Site-level dataset, across
studies .xpt
III.C data-listing-data-
definition Define file 	.xml
Optional 	data-listing-dataset BIMO Data Reviewer’s
Guide .pdf
288
B. 	eCTD Folder Structure for Clinical Study-Level Information and Subject-	289
Level Line Listings by Clinical Site	290
291
Clinical study-level information and subject-level line listings by clinical site are submitted for	292
each major (i.e., pivotal) study used to support safety and efficacy in the application.	293
294
Within the eCTD folder structure, place clinical study-level information and subject-level line	295
listings by clinical site in the M5 folder as follows:	296
297
Figure 2: Place Clinical Study-Level Information and Subject-Level Line Listings by	298
Clinical Site in the M5 Folder	299
300
301
302
C. 	eCTD Folder Structure for Summary-Level Clinical Site Dataset	303
304
For the site-level dataset, use the filename “clinsite.xpt.” A single file containing data from all	305
major (i.e., pivotal) studies9 used to support safety and efficacy in the application should be	306
provided.	307
9 For questions regarding whether a study is considered major (i.e., pivotal), applicants should consult the relevant
Office of New Drugs review division during Type C Integrated Summary of Safety or pre NDA/BLA meetings.

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308
Within the eCTD folder structure, place the site-level dataset define file and BIMO Data	309
Reviewer’s Guide, if it is being submitted, in the M5 folder as follows:	310
311
Figure 2: Place the Site-Level Dataset Define File and BIMO Data Reviewer’s Guide in the	312
M5 Folder	313
314
315
316
D. 	File Format	317
318
The Clinical Study-Level Information and Subject-Level Data Line Listings by Clinical Site	319
should be submitted in PDF (*.pdf). When submitting a BIMO Data Reviewer’s Guide, it should	320
also be submitted in PDF (*.pdf). The summary-level clinical site data should be submitted in	321
SAS transport file format (*.xpt). The define file for the summary-level clinical site data should	322
be submitted in Extensible Markup Language (define.xml) format. For more information, see	323
the Study Data Technical Conformance Guide.10	
324
E. 	Leaf Titles	325
326
Leaf titles for study-level information and study-level, subject-level data line listings by clinical	327
site are named “BIMO [list study ID, followed by brief description of file being submitted].” For	328
the leaf representing the clinsite.xpt dataset, please clearly identify it with the leaf title “BIMO	329
summary-level clinical site data.”	330
331
F. 	Submission	332
333
See the technical specifications in Transmitting Electronic Submissions Using eCTD	334
Specifications for details on electronic transmission or physical media submissions.11	
335
336
The following are helpful references for eCTD submission:	337
10 Available at https://www.fda.gov/industry/fda-resources-data-standards/study-data-standards-resources.
11 Available at
http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSub
missions/UCM163567.pdf.

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• 	ICH eCTD STF Specification V 2.6.1, The eCTD Backbone File Specification for Study	338
Tagging Files (June 2008) (available at https://www.fda.gov/media/159383/download).	339
• 	FDA guidance for industry Providing Regulatory Submissions in Electronic Format –	340
Certain Human Pharmaceutical Product Applications and Related Submissions Using the	341
eCTD Specifications (February 2020) (available at https://www.fda.gov/regulatory-	342
information/search-fda-guidance-documents).	343
• 	FDA eCTD web page	344
(http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/E	345
lectronicSubmissions/ucm153574.htm ).	346
• 	For general help with eCTD submissions, submit your questions to the following email	347
address: ESUB@fda.hhs.gov.	348
349
350

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APPENDIX 1: CLINICAL STUDY-LEVEL INFORMATION	351
352
Format for comprehensive and readily located list of all clinical sites that participated in each	353
clinical study. A separate table should be provided for each clinical study.	354
Table A: Format for Clinical Site Lists	355
Protocol Number: Protocol Title
Site
Identifier
Investigator
Name
(Prior Clinical
Investigator(s))
Site Address at Time of
Clinical Study
(Updated Site Address
when exists and available)
Site Contact
Information at Time
of Clinical Study
(Updated Contact
Information when
exists and available)
SITEID 	LASTNAME,
FRSTNAME,
MINITIAL
FACILITY NAME
STREET
CITY, STATE, POSTAL
COUNTRY
PHONE
FAX
EMAIL
0001* 	Doe, John M. 	Doe University Department of
Medicine
1 Main St., Suite 100
Silver Spring, MD 20850
USA
Phone: 1-555-555-5555
Fax: 1-555-555-5555
Email:
john.doe@mail.com
0002 	Doe, Jean
(Smith, John)
Doe University Department of
Medicine
1 Main St., Suite 100
Silver Spring, MD 20850
USA
Phone: 1-555-555-5555
Fax: 1-555-555-5555
Email:
john.smith@mail.com
(Phone: 1-555-555-5554
Email:
jean.doe@mail.com )
003 	Dietric-Fischer,
Inge
Hartmannstrasse 7
5300 Bonn 1
Germany
Phone:49-555-555-5555
Fax: 49-555-555-5555
Email:
Dietric.Fischer@web.de
* Site terminated, or clinical investigator changed, at request of sponsor before study
completion.
356
357

Contains Nonbinding Recommendations
12
APPENDIX 2: FORMATTING SUBJECT-LEVEL DATA LINE LISTINGS BY	358
CLINICAL SITE	359
360
By Site, by Listing Option A:	361
362
Figure A: By Site, by Listing Option A	363
364
365
366
By Site, by Subject Profile Option B:	367
368
Figure B: By Site, by Subject Profile Option B	369
370
371
Protocol Number
Next Site Number
Next Site Number
Site Number
Subject Number
Next Subject Number
Next Subject Number
+
+
-
Subject Profile That Containing
All Elements of Requested Line
Listings for this Subject
-
+
+
Protocol Number
Next Site Number
Next Site Number
Site Number
Listing “1”
Listing “2”
Listing “3”
Listing “4”
Etc.
+
+
-
Etc.
Etc.

Contains Nonbinding Recommendations
13
Example of By Site, by Listing Option A:	372
373
Figure C: Example of By Site, by Listing Option A	374
375
376
Example of By Site, by Listing Option B:	377
378
Figure D: Example of By Site, by Listing Option B	379
380
Protocol #1234
Site #0002
Site #0003
Site #0001
Subject Number #0001-001
Subject Number #0001-101
Subject Number #0001-064
+
+
-
Subject Profile Containing
All Elements of Requested
Line Listings for this Subject
-
+
+
Protocol #1234
Site #0002
Site #0003
Site #0001
Consented Subjects
Treatment Assignment
Discontinuations
Study Population
Etc.
+
+
-
Etc.
Etc.

Contains Nonbinding Recommendations
14
APPENDIX 3: CLINICAL SITE DATA ELEMENTS SUMMARY LISTING
Table B: Clinical Site Data Elements Summary Listing
Variable
Index Variable Name 	Variable Label 	Type 	Controlled Terms or
Format Notes or Description 	Sample Value
1 	STUDYID 	Study Identifier 	Char 	String 	Study or trial identification number. 	ABC-123
2 	TITLE 	Study Title 	Char 	String 	Title of the study as listed in the clinical study report
(limit 200 characters).
If the title exceeds 200 characters, provide
shortened title and define (e.g., use the abbreviated
title from clinicaltrial.gov).
Double blind,
randomized, placebo-
controlled clinical
study on the influence
of drug X on indication
Y
3 	SPONCNT 	Sponsor Count 	Num 	Integer 	Total count of sponsors throughout the study. If
there was a change in the sponsor while the study
was ongoing, with sponsors as defined in § 312.3
(21 CFR 312.3), enter an integer indicating the total
count of sponsors. If there was no change in the
sponsor while the study was ongoing, enter “1.”
1
4 	SPONSOR 	Sponsor Name 	Char 	String 	Full name of the sponsor organization conducting
the study at the time of study completion, as
sponsor is defined in § 312.3. If the sponsor name
exceeds 200 characters, provide short-form sponsor
name and define.
DrugCo, Inc.
5 	IND 	IND Number 	Num 	6 digit identifier 	IND number. If study not performed under IND,
leave blank.
010010
6 	UNDERIND 	Under IND 	Char 	String 	Value should equal “Y” if study at the site was
conducted under an IND (i.e., a Form FDA 1572
was signed by the investigator) and “N” if study was
not conducted under an IND at the site (i.e., a Form
FDA 1572 was not signed by the investigator).
Y
7 	NDA 	NDA Number 	Num 	6 digit identifier 	FDA NDA number, if available/applicable. If not
applicable, leave blank.
021212
8 	BLA 	BLA Number 	Num 	6 digit identifier 	FDA identification number for BLA, if
available/applicable. If not applicable, leave blank.
123456
9 	SUPPNUM 	Supplement
Number
Num 	Integer 	Serial number for supplemental application, if
applicable. If no information is available, leave
blank.
4
10 	SITEID 	Study Site
Identifier
Char 	String 	Investigator site identifier assigned by the sponsor. 	50
11 	ARM 	Description of
Planned
Treatment Arm
Char 	String 	Plain-text label for the name given to an arm or
treatment group as referenced in the clinical study
report (limit 200 characters). When no arm or
treatment group is available due to only screen
failure subjects at site, use label “Screen Failure.”
Active name and dose
(e.g., “Active 25mg”),
Comparator product
name (e.g., “Drug x”),
Placebo, Screen
Failure

Contains Nonbinding Recommendations
15
Variable
Index Variable Name 	Variable Label 	Type 	Controlled Terms or
Format Notes or Description 	Sample Value
12 	COHORT 	Description of
Planned Cohort
Char 	String 	For cohort studies, the plain-text label given to a
cohort as referenced in the clinical study report (limit
200 characters). When not a cohort study, leave
blank.
A
13 	SAFPOP 	Number of
Subjects in
Safety
Population
Num 	Integer 	Total number of subjects in safety population at a
given site by treatment arm. When a subject has
transferred from one site to another, the applicant
should handle reporting of such subjects
consistently across sites and include in the define
file the reporting convention used. The applicant
may opt to further explain the reasons subjects
transferred between sites in the BIMO Data
Reviewer’s Guide, if a guide will be provided.
20
14 	EFFPOP 	Number of
Subjects in
Efficacy
Population
Num 	Integer 	Total number of subjects in primary efficacy
population as reported in the Clinical Study Report
at a given site by treatment arm. Further describe
the population reported as EFFPOP (e.g.,. Per
Protocol, Full Analysis Set, Intent to Treat, modified
Intent to Treat) in the clinsite define.html. When a
subject has transferred from one site to another, the
applicant should handle reporting of such subjects
consistently across sites and include in the define
file the reporting convention used. The applicant
may opt to further explain the reasons subjects
transferred between sites in the BIMO Data
Reviewer’s Guide, if a guide will be provided.
18
15 	SCREEN 	Number of
Subjects
Screened
Num 	Integer 	Total number of subjects screened (and consented)
at a given site (overall number per site as subjects
have not yet been assigned to treatment arm).
When a subject has transferred from one site to
another, the applicant should handle reporting of
such subjects consistently across sites and include
the reporting convention used in the define file or the
BIMO Data Reviewer’s Guide (if provided). The
applicant may opt to further explain the reasons
subjects transferred between sites in the BIMO Data
Reviewer’s Guide, if provided.
100
16 	DISCSTUD 	Number
Subjects
Discont. Study
Num 	Integer 	Number of subjects in the safety population who
discontinued from the study by treatment arm at a
given site.
5
17 	DISCTRT 	Number
Subjects
Discont. Study
Treatment
Num 	Integer 	Number of subjects in the safety population who
discontinued from the study treatment by treatment
arm at a given site.
10
18 	ENDPOINT 	Primary
Endpoint
Char 	String 	Plain-text label used to describe the primary
endpoint as described in the define file included with
each application (limit 200 characters).
Average increase in
blood pressure

Contains Nonbinding Recommendations
16
Variable
Index Variable Name 	Variable Label 	Type 	Controlled Terms or
Format Notes or Description 	Sample Value
19 	ENDPTYPE 	Primary
Endpoint Type
Char 	String 	Variable type of the primary endpoint (i.e.,
“continuous,” “discrete,” “time to event,” or “other”).
Continuous
20 	TRTEFFR1 	Treatment
Efficacy Result
for SAFPOP
Num 	Floating Point 	Summary statistic for each primary efficacy endpoint
by treatment arm at a given site for subjects in
SAFPOP.
1.00
21 	TRTEFFR2 	Treatment
Efficacy Result
for EFFPOP
Num 	Floating Point 	Summary statistic for each primary efficacy endpoint
by treatment arm at a given site for subjects in
EFFPOP.
0.98
22 	CENSOR1 	Censored
Observations in
SAFPOP
Num 	Integer 	Total number of censored observations in SAFPOP
at a given site by treatment arm for primary endpoint
(e.g., applicable to time-to-event). If not applicable,
leave blank.
5
23 	CENSOR2 	Censored
Observations in
EFFPOP
Num 	Integer 	Total number of censored observations in EFFPOP
at a given site by treatment arm for primary endpoint
(e.g., applicable to time-to-event). If not applicable,
leave blank.
3
24 	NSAE 	Number of Non-
Serious
Adverse Events
Num 	Integer 	Total number of nonserious adverse events at a
given site by treatment arm for subjects in the
SAFPOP. This value should include multiple events
per subject and all event types (i.e., not limited to
only those that are deemed related to study drug or
that are treatment emergent events). When events
with the same preferred term have occurred on
different dates for a subject, each event should be
counted separately in event count.
10
25 	SAE 	Number of
Serious
Adverse Events
Num 	Integer 	Total number of serious adverse events, excluding
deaths, at a given site by treatment arm for subjects
in the SAFPOP. This value should include multiple
events per subject. When events with the same
preferred term have occurred on different dates for a
subject, each event should be counted separately in
event count.
5
26 	DEATH 	Number of
Deaths
Num 	Integer 	Total number of deaths at a given site by treatment
arm for subjects in the SAFPOP.
1
27 	IMPDEV 	Number of
Important
Protocol
Deviations
Num 	Integer 	Total number of important protocol deviations at a
given site by treatment arm for subjects in the
SAFPOP. A protocol deviation is any change,
divergence, or departure from the study design or
procedures defined in the protocol or associated
investigational plans that is not implemented or
intended as a systematic change. This value should
include multiple deviations per subject and all major
deviation types. Important deviations are those
deviations that might significantly affect the
completeness, accuracy, and/or reliability of the
study data or that might significantly affect a
subject's rights, safety, or well-being.
2

Contains Nonbinding Recommendations
17
Variable
Index Variable Name 	Variable Label 	Type 	Controlled Terms or
Format Notes or Description 	Sample Value
28 	NOIMPDEV 	Number of Non-
Important
Protocol
Deviations
Num 	Integer 	Total number of protocol deviations, excluding
important protocol deviations, at a given site by
treatment arm for subjects in the SAFPOP. A
protocol deviation is any change, divergence, or
departure from the study design or procedures
defined in the protocol or associated investigational
plans that is not implemented or intended as a
systematic change.
98
29 	FINLDISC 	Financial
Disclosure
Amount
Char 	String 	Total financial disclosure amount (US$) by site
calculated as the sum of disclosures for the clinical
investigator and all sub-investigators, to include all
required parities under the applicable regulations
(21 CFR 54, 312, 314, 320, 330, 601, 807, 812, 814,
and 860). Enter “>=$25,000,” “< $25,000,”
“unknown” if a proper value is applicable but is not
known (i.e., unable to obtain information from
investigator at site), or “masked” if information on
this item is available but it has not been provided by
the sender due to security, privacy, or other
reasons.
>= $25,000
30 	LASTNAME 	Investigator
Last Name
Char 	String 	Last name of the clinical investigator as it appears
on the Form FDA 1572 or the signed investigator
agreement. At sites where the clinical investigator
has changed during the course of the study, the
most recent clinical investigator should be listed.
Doe
31 	FRSTNAME 	Investigator
First Name
Char 	String 	First name of the clinical investigator as it appears
on the Form FDA 1572 or the signed investigator
agreement.
John
32 	MINITIAL 	Investigator
Middle Initial
Char 	String 	Middle initial of the clinical investigator, if any, as it
appears on the Form FDA 1572 or the signed
investigator agreement.
M
33 	PHONE 	Investigator
Phone Number
Char 	String 	Phone number of the clinical investigator. Include
country code for non-U.S. numbers.
44-555-555-5555
34 	FAX 	Investigator Fax
Number
Char 	String 	Fax number of the clinical investigator. Include
country code for non-U.S. numbers. If not available,
leave blank.
44-555-555-5555
35 	EMAIL 	Investigator
Email Address
Char 	String 	Email address of the clinical investigator. 	John.doe@mail.com
36 	COUNTRY 	Country 	Char 	Geopolitical Entities,
Names and Codes
(GENC)
GENC code for the country in which the site is
located.
USA

Contains Nonbinding Recommendations
18
Variable
Index Variable Name 	Variable Label 	Type 	Controlled Terms or
Format Notes or Description 	Sample Value
37 	STATE 	State 	Char 	GENC 	GENC subdivision unabbreviated preferred name in
which the site is located. If not applicable, enter
“NA.”
Maryland
38 	CITY 	City 	Char 	String 	Unabbreviated city or village in which the site is
located.
Silver Spring
39 	POSTAL 	Postal Code 	Char 	String 	Postal code in which the site is located. If not
applicable, enter “NA.”
20850
40 	STREET 	Street Address 	Char 	String 	Street address and office number at which the site is
located (limit 200 characters).
2005 John Fitzgerald
Kennedy Boulevard
Northwest,
International
Technology Center,
Department of
Medicine and
Pharmacokinetics,
National Institute of
Clinical Research
Twin Towers Building,
41 	STREET1 	Street Address
Continued
Char 	String 	Street address and office number at which the site is
located. Use this field when the STREET variable
does not permit sufficient space to fully describe
street address and office number at which the site is
located.
The Executive Wing,
Suite # 209

Contains Nonbinding Recommendations
19
APPENDIX 4: EXAMPLES
The following is a fictional example of a dataset for a placebo-controlled trial. Four international sites enrolled a total of 205 subjects
who were randomized in a 1:1 ratio to active or placebo. In the first example there is a single primary endpoint (percent of
responders). In the second example there are co-primary endpoints (percent of responders and change from baseline). Note that since
there were two treatment arms, in the first example, each site contains two rows and there are a total of eight rows for the entire
dataset. In the second example, each site contains a total of 4 rows, and there are a total of 16 rows for the entire dataset.
Table C: Example for Clinical Site Data Elements Summary Listing with One Endpoint
STUDYID 	TITLE 	SPONCNT 	SPONSOR 	IND 	UNDER-
IND 	NDA 	BLA 	SUPP-
NUM 	SITEID 	ARM 	COHORT 	SAFPOP 	EFFPOP 	SCREEN 	DISCSTUD 	DISCTRT
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	001 	Active 	- 	26 	54 	61 	3 	2
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	001 	Placebo 	- 	25 	54 	61 	4 	1
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	002 	Active 	- 	23 	44 	54 	2 	1
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	002 	Placebo 	- 	25 	43 	54 	4 	3
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	003 	Active 	- 	27 	55 	62 	3 	0
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	003 	Placebo 	- 	26 	56 	62 	5 	3
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	004 	Active 	- 	26 	49 	60 	2 	2
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	004 	Placebo 	- 	27 	50 	60 	1 	0
ENDPOINT 	ENDPTYPE 	TRTEFFR1 	TRTEFFR2 	CENSOR1 	CENSOR2 	NSAE 	SAE 	DEATH 	IMPDEV 	NOIMPDEV 	FINLDISC 	LASTNAME 	FRSTNAME
Percent
Responders 	Binary 	0.48 	0.64 	∙ 	- 	0 	2 	0 	1 	4 	< $25,000 	Doe 	John
Percent
Responders 	Binary 	0.14 	0.19 	∙ 	- 	2 	2 	0 	1 	6 	< $25,000 	Doe 	John
Percent
Responders 	Binary 	0.48 	0.42 	∙ 	- 	3 	2 	1 	0 	9 	>= $25,000 	Washington 	George
Percent
Responders 	Binary 	0.14 	0.20 	∙ 	- 	0 	2 	0 	3 	11 	>= $25,000 	Washington 	George
Percent
Responders 	Binary 	0.54 	0.48 	∙ 	- 	2 	2 	0 	1 	4 	>= $25,000 	Jefferson 	Thomas
Percent
Responders 	Binary 	0.19 	0.32 	∙ 	- 	3 	6 	0 	0 	7 	>= $25,000 	Jefferson 	Thomas
Percent
Responders 	Binary 	0.46 	0.45 	∙ 	- 	4 	1 	0 	0 	8 	unknown 	Lincoln 	Abraham
Percent
Responders 	Binary 	0.12 	0.16 	∙ 	- 	1 	2 	0 	1 13 unknown 	Lincoln 	Abraham
MINITIAL 	PHONE 	FAX 	EMAIL 	COUNTRY 	STATE 	CITY 	POSTAL 	STREET 	STREET1
M 	555-123-4567 	555-123-4560 	John@mail.com 	RUS 	Moskovskaya
Oblast’ 	Moscow 	103009 	Kremlin Road 1
M 	555-123-4567 	555-123-4560 	John@mail.com 	RUS 	Moskovskaya
Oblast’ 	Moscow 	103009 	Kremlin Road 1
020-3456-7891 	020-3456-7890 	george@mail.com 	GBR 	Westminster 	London 	SW1A 2 	10 Downing St

Contains Nonbinding Recommendations
20
020-3456-7891 	020-3456-7890 	george@mail.com 	GBR 	Westminster 	London 	SW1A 2 	10 Downing St
01-89-12-34-56 	01-89-12-34-51 	tom@mail.com 	FRA 	Paris 	Paris 	75002 	1, Rue Road
01-89-12-34-56 	01-89-12-34-51 	tom@mail.com 	FRA 	Paris 	Paris 	75002 	1, Rue Road
555-987-6543 	555-987-6540 	abe@mail.com 	USA 	Maryland 	Rockville 	20852
10903 New Hampshire Avenue,
Office of Medical Products and
Tobacco, Center for Drug
Evaluation and Research
Building 4,
Room 1375
555-987-6543 	555-987-6540 	abe@mail.com 	USA 	Maryland 	Rockville 	20852
10903 New Hampshire Avenue,
Office of Medical Products and
Tobacco, Center for Drug
Evaluation and Research
Building 4,
Room 1375
Table D: Example for Clinical Site Data Elements Summary Listing with Multiple Primary Endpoints
STUDYID 	TITLE 	SPONCNT 	SPONSOR 	IND 	UNDER-
IND 	NDA 	BLA 	SUPP-
NUM 	SITEID 	ARM 	COHORT 	SAFPOP 	EFFPOP 	SCREEN 	DISCSTUD 	DISCTRT
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	001 	Active 	A 	26 	22 	61 	3 	2
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	001 	Active 	B 	26 	22 	61 	3 	2
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	001 	Placebo 	A 	25 	23 	61 	4 	1
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	001 	Placebo 	B 	25 	23 	61 	4 	1
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	002 	Active 	A 	23 	19 	54 	2 	1
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	002 	Active 	B 	23 	19 	54 	2 	1
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	002 	Placebo 	A 	25 	23 	54 	4 	3
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	002 	Placebo 	B 	25 	23 	54 	4 	3
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	003 	Active 	A 	27 	26 	62 	3 	0
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	003 	Active 	B 	27 	26 	62 	3 	0
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	003 	Placebo 	A 	26 	23 	62 	5 	3
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	003 	Placebo 	B 	26 	23 	62 	5 	3
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	004 	Active 	A 	26 	19 	60 	2 	2
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	004 	Active 	B 	26 	19 	60 	2 	2
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	004 	Placebo 	A 	27 	20 	60 	1 	0
ABC-123 	Double
blind… 	1 	DrugCo, Inc. 	000001 	Y 	200001 	∙ 	∙ 	004 	Placebo 	B 	27 	20 	60 	1 	0
ENDPOINT 	ENDPTYPE 	TRTEFFR1 	TRTEFFR2 	CENSOR1 	CENSOR2 	NSAE 	SAE 	DEATH 	IMPDEV 	NOIMPDEV 	FINLDISC 	LASTNAME 	FRSTNAME
Percent Responders 	Binary 	0.48 	0.58 	∙ 	∙ 	0 	2 	0 	1 	5 	< $25,000 	Doe 	John
Change from
Baseline 	Continuous 	0.74 	0.76 	∙ 	∙ 	0 	2 	0 	1 	8 	< $25,000 	Doe 	John
Percent Responders 	Binary 	0.14 	0.12 	∙ 	∙ 	2 	2 	0 	1 	5 	< $25,000 	Doe 	John
Change from
Baseline 	Continuous 	0.14 	0.16 	∙ 	∙ 	2 	2 	0 	1 	8 	< $25,000 	Doe 	John
Percent Responders 	Binary 	0.48 	0.44 	∙ 	∙ 	3 	2 	1 	0 	11 	>= $25,0000 	Washington 	George

Contains Nonbinding Recommendations
21
ENDPOINT 	ENDPTYPE 	TRTEFFR1 	TRTEFFR2 	CENSOR1 	CENSOR2 	NSAE 	SAE 	DEATH 	IMPDEV 	NOIMPDEV 	FINLDISC 	LASTNAME 	FRSTNAME
Change from
Baseline 	Continuous 	0.67 	0.63 	∙ 	∙ 	3 	2 	1 	0 	13 	>= $25,0000 	Washington 	George
Percent Responders 	Binary 	0.14 	0.15 	∙ 	∙ 	0 	2 	0 	3 	11 	>= $25,0000 	Washington 	George
Change from
Baseline 	Continuous 	0.14 	0.16 	∙ 	∙ 	0 	2 	0 	3 	13 	>= $25,0000 	Washington 	George
Percent Responders 	Binary 	0.54 	0.50 	∙ 	∙ 	2 	2 	0 	1 	9 	>= $25,0000 	Jefferson 	Thomas
Change from
Baseline 	Continuous 	0.65 	0.61 	∙ 	∙ 	2 	2 	0 	1 	5 	>= $25,0000 	Jefferson 	Thomas
Percent Responders 	Binary 	0.19 	0.22 	∙ 	∙ 	3 	6 	0 	0 	9 	>= $25,0000 	Jefferson 	Thomas
Change from
Baseline 	Continuous 	0.19 	0.26 	∙ 	∙ 	3 	6 	0 	0 	5 	>= $25,0000 	Jefferson 	Thomas
Percent Responders 	Binary 	0.46 	0.51 	∙ 	∙ 	4 	1 	0 	0 	0 	unknown 	Lincoln 	Abraham
Change from
Baseline 	Continuous 	0.71 	0.81 	∙ 	∙ 	4 	1 	0 	0 	3 	unknown 	Lincoln 	Abraham
Percent Responders 	Binary 	0.12 	0.17 	∙ 	∙ 	1 	2 	0 	0 0 unknown 	Lincoln 	Abraham
Change from
Baseline 	Continuous 	0.15 	0.19 	∙ 	∙ 	1 	2 	0 	1 3 unknown 	Lincoln 	Abraham
MINITIAL 	PHONE 	FAX 	EMAIL 	COUNTRY 	STATE 	CITY 	POSTAL 	STREET 	STREET1
M 	555-123-4567 	555-123-4560 	John@mail.com 	RUS 	Moskovskaya
Oblast’ 	Moscow 	103009 	Kremlin Road 1
M 	555-123-4567 	555-123-4560 	John@mail.com 	RUS 	Moskovskaya
Oblast’ 	Moscow 	103009 	Kremlin Road 1
M 	555-123-4567 	555-123-4560 	John@mail.com 	RUS 	Moskovskaya
Oblast’ 	Moscow 	103009 	Kremlin Road 1
M 	555-123-4567 	555-123-4560 	John@mail.com 	RUS 	Moskovskaya
Oblast’ 	Moscow 	103009 	Kremlin Road 1
∙ 	020-3456-7891 	020-3456-7890 	george@mail.com 	GBR 	Westminster 	London 	SW1A 2 	10 Downing St Suite 2058
∙ 	020-3456-7891 	020-3456-7890 	george@mail.com 	GBR 	Westminster 	London 	SW1A 2 	10 Downing St Suite 2058
∙ 	020-3456-7891 	020-3456-7890 	george@mail.com 	GBR 	Westminster 	London 	SW1A 2 	10 Downing St Suite 2058
∙ 	020-3456-7891 	020-3456-7890 	george@mail.com 	GBR 	Westminster 	London 	SW1A 2 	10 Downing St Suite 2058
∙ 	01-89-12-34-56 	01-89-12-34-51 	tom@mail.com 	FRA 	Paris 	Paris 	75002 	1, Rue Road
∙ 	01-89-12-34-56 	01-89-12-34-51 	tom@mail.com 	FRA 	Paris 	Paris 	75002 	1, Rue Road
∙ 	01-89-12-34-56 	01-89-12-34-51 	tom@mail.com 	FRA 	Paris 	Paris 	75002 	1, Rue Road
∙ 	01-89-12-34-56 	01-89-12-34-51 	tom@mail.com 	FRA 	Paris 	Paris 	75002 	1, Rue Road
∙
555-987-6543 	555-987-6540 	abe@mail.com 	USA 	Maryland 	Rockville 	20852
2005 John Fitzgerald Kennedy Boulevard Northwest,
International Technology Center, Department of
Medicine and Pharmacokinetics, National Institute of
Clinical Research Twin Towers Building,
The Executive
Wing, Suite # 209
∙
555-987-6543 	555-987-6540 	abe@mail.com 	USA 	Maryland 	Rockville 	20852
2005 John Fitzgerald Kennedy Boulevard Northwest,
International Technology Center, Department of
Medicine and Pharmacokinetics, National Institute of
Clinical Research Twin Towers Building,
The Executive
Wing, Suite # 209
∙
555-987-6543 	555-987-6540 	abe@mail.com 	USA 	Maryland 	Rockville 	20852
2005 John Fitzgerald Kennedy Boulevard Northwest,
International Technology Center, Department of
Medicine and Pharmacokinetics, National Institute of
Clinical Research Twin Towers Building,
The Executive
Wing, Suite # 209
∙ 	555-987-6543 	555-987-6540 	abe@mail.com 	USA 	Maryland 	Rockville 	20852 	2005 John Fitzgerald Kennedy Boulevard Northwest, 	The Executive

Contains Nonbinding Recommendations
22
MINITIAL 	PHONE 	FAX 	EMAIL 	COUNTRY 	STATE 	CITY 	POSTAL 	STREET 	STREET1
International Technology Center, Department of
Medicine and Pharmacokinetics, National Institute of
Clinical Research Twin Towers Building,
Wing, Suite # 209