Study Data Reviewer’s Guide
A One-Month Oral Toxicology Study in the Rat with C1234 followed by a One-Month
Recovery Period
(Study 12345)
A Pharma Company
500 Farm Road
West Orange, New Jersey 07052
United States
CONTENTS
1. Introduction 3
1.1 Study Protocol Title, Number, and Report Version 3
1.2 Summary of SEND Dataset Creation Process 3
1.3 SEND Dataset Verification 3
2. Study Design 3
2.1 Study Design Summary 3
2.2 Trial Design Domain Overview 4
3. Standards, Formats, Terminologies and their Versions 4
3.1 Standards Used 4
3.2 Rationale for Standards Selection 4
3.3 Nonstandard Terminology 4
4. Description of Study Datasets 5
4.1 Dataset Summary 5
4.2 Use of Supplemental Qualifiers 6
5. Data Standards, Validation Rules, Versions, and Conformance Issues 6
5.1 Validation Outcome Summary 6
5.2 Validation Method Used 6
5.3 Errors 6
5.4 Warnings 6
5.5 Notices 6
6. Description of Sponsor Decisions Related to Data Standard Implementations 7
6.1 Sponsor-Defined Standardization Descriptions 7
6.2 Differences between SEND Datasets and Study Report 7
6.3 Nonstandard Electronic Data Submitted 7
1. Introduction
1.1 Study Protocol Title, Number, and Report Version
Study Title / A One-Month Repeat-Dose Oral Toxicology Study in the Rat with C1234 followed by a One-Month Recovery PeriodStudy Number / 12345
Study Version / There have been no report amendments.
1.2 Summary of SEND Dataset Creation Process
All in-life, clinical pathology, and postmortem data were collected using LIMS 1 (Vendor). Bioanalytical data (plasma drug concentrations) were determined using LIMS 2 (Vendor). Pharmacokinetic parameters were calculated in Excel. Input (raw data) from each of the LIMS and the Excel PK calculations via LIMS and Excel-specific adaptors was processed by SEND solution XXX (Vendor) to produce one integrated SEND dataset, a define XML and PDF file, and a validation report. SEND solution XXX and the adaptors are Part 11 compliant.
1.3 SEND Dataset Verification
Data in the SEND datasets are an accurate representation of data in the study report for Study No. 12345. Any differences between the datasets and the report are described in Section 6.2.
2. Study Design
2.1 Study Design Summary
In study 12345, C1234 was given to male and female rats by oral gavage at doses of 0 (vehicle control), 10, 30, and 100 mg/kg/day for 28 consecutive days followed by a two-month recovery period for the control and high doses.
2.2 Trial Design Domain Overview
Study Group / Trial Arms / Element in each Epoch / Trial SetSPGRPCD / ARMCD / ARM / Predosing / Treatment / Recovery / SETCD / SET
1 / 01 / 0 mg/kg Vehicle / Predosing / Vehicle / 01 / 0 mg/kg Vehicle Main
01TK / 0 mg/kg Vehicle TK
01R / 0 mg/kg Recovery / Predosing / Vehicle Recovery / Recovery / 01R / 0 mg/kg Vehicle Recovery
2 / 02 / 10 mg/kg C1234 / Predosing / 10 mg/kg / 02 / 10 mg/kg C1234 Main
02TK / 10 mg/kg C1234 TK
3 / 03 / 30 mg/kg C1234 / Predosing / 30 mg/kg / 03 / 30 mg/kg C1234Main
03TK / 30 mg/kg C1234 TK
4 / 04 / 100 mg/kg C1234 / Predosing / 100 mg/kg / 04 / 100 mg/kg C1234 Main
04TK / 100 mg/kg C1234 TK
04R / 100 mg/kg C1234 Recovery / Predosing / 100 mg/kg Recovery / Recovery / 04R / 100 mg/kg C1234 Recovery
3. Standards, Formats, Terminologies and their Versions
3.1 Standards Used
Standard or Dictionary / Standard or Dictionary / Versions Used /Tabulation Datasets / CDISC SEND / 3.0
Data Definition file / CDISC DEFINE.XML / 1.0
Controlled Terminology / CDISC SEND Controlled Terminology / 2014-12-26
Tabulation Dataset Validator / Open CDISC / 1.4
3.2 Rationale for Standards Selection
The standards versions used were the most current ones listed in FDA’s Study Data Standards Catalog at the time of dataset creation.
3.3 Nonstandard Terminology
The following nonstandard terminology was used. It was submitted to NCI for consideration, but no resolution was received prior to dataset creation:
Dataset Name / Variable / Codelist / Term Used / Meaning /LB / LBTEST / LBTEST / Melamine abutyltransferfree / A measurement of the melamine abutyltransferfree in a biological specimen.
LB / LBTESTCD / LBTESTCD / MELTRFRE / A measurement of the melamine abutyltransferfree in a biological specimen.
4. Description of Study Datasets
4.1 Dataset Summary
Dataset Name / Dataset Label / Supplemental Qualifiers? / Observation Class /TA / Trial Arms / Trial Design
TE / Trial Elements / Trial Design
TS / Trial Summary / Trial Design
TX / Trial Sets / Trial Design
CO / Comments / Special Purpose
DM / Demographics / Special Purpose
SE / Subject Elements / Special Purpose
EX / Exposure / Interventions
DS / Disposition / Events
BW / Body Weight / Findings
BG / Body Weight Gain / Findings
CL / Clinical Observations / Findings
FW / Food and Water Consumption / Findings
LB / Laboratory Test Results / Findings
MA / Macroscopic Findings / X / Findings
MI / Microscopic Findings / X / Findings
OM / Organ Measurements / Findings
PC / Pharmacokinetic Concentrations / Findings
PP / Pharmacokinetic Parameters / Findings
RELREC / Related Records / Relationship
POOLDEF / Pooled Definition / Relationship
Define.xml / Data Definition File
4.2 Use of Supplemental Qualifiers
Dataset Name / Associated Dataset / Qualifiers Used /SUPPMA / Macroscopic Observations / Modifiers that were part of MAORRES which SEND variables have not yet been developed.
SUPPMI / Microscopic Observations / Modifiers that were part of MIORRES which SEND variables have not yet been developed.
5. Data Standards, Validation Rules, Versions, and Conformance Issues
5.1 Validation Outcome Summary
There were no conformance errors or issues that impacted the quality of these SEND datasets.
5.2 Validation Method Used
OpenCDISC Validator Version 1.4 was used to evaluate conformance to SEND 3.0.
5.3 Errors
There were no errors reported.
5.4 Warnings
The following warnings were reported:
OpenCDISC (1.4) Rule / FDA (2.1) Rule / Message / Domain(s) / Count / Explanation /SD1117 / FDAN212 / Duplicate records / LB, MA, MI, PP / 216 / The variables considered for uniqueness by SD1117 / FDAN212 do not include a sufficient number to determine uniqueness. For example, ORRES was not included. We therefore do not consider these warnings to be applicable.
5.5 Notices
OpenCDISC (1.4) Rule / FDA (2.1) Rule / Message / Domain(s) / Count / Explanation /SD1076 / FDAN031 / Model permissible variable added into standard domain / CL / 1 / The permissible variable included in the Cl (clinical observations) domain was CLREFID (clinical observations reference identifier).
6. Description of Sponsor Decisions Related to Data Standard Implementations
6.1 Sponsor-Defined Standardization Descriptions
There were no custom domains or custom endpoints for this study.
6.2 Differences between SEND Datasets and Study Report
The first day of dosing in the report and protocol is Day 0. The first day of dosing in the SEND datasets is Day 1 in compliance with SEND. Accordingly, all study days starting with the first day of dosing in the SEND dataset are 1 day later than the corresponding day in the protocol and study report.
6.3 Nonstandard Electronic Data
Ocular data was provided in a non-standard format, since there is no SEND 3.0 domain definition for this data. Refer to the file Ocular_def.txt for format details.
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