To change this title, go to Notes Master 4/6/2017 SDTM IG 3.1.4 (Batch 1 – Release for Public Review) Standards for Therapeutic Areas Quintiles QBLM SDTM Forum

To change this title, go to Notes Master 4/6/2017 Part 1: SDTM IG 3.1.4 (Batch 1 – Release for Public Review) Quintiles QBLM SDTM Forum

To change this header/title, go to Notes Master SDTM-IG 3.1.4 (Batch 1) 4/6/2017 http://www.cdisc.org/sdtm Public review Aug/Sep Batch 1 Released for Public Review Aug/Sept 2012 - these domains may still undergo changes due to suggested enhancements or responses to comments from the Public Review Documents in Batch 1 will not be considered final until they are incorporated in the official posting of the SDTM 1.4 and SDTM-IG 3.1.4. At such time, Batch 1 will cease to exist in draft form and its various components will take their place within the appropriate SDTM-IG sections. Given the volume of new specialty IG and domains, the SDS Team decided to divide materials targeted for inclusion in SDTM-IG 3.1.4 into two manageable batches for public review Batch 1 package: Exposure Domains Supplement: Clarification on variables, Added/Updated Variables Variables proposed for Deprecation New domain is introduced, Exposure as Collected (EC). Immunogenicity Domains Supplement: Immunogenicity Specimen Assessments (IS) {Findings Domain} Skin Response (SR) {Findings About Domain} Reproductive Details Domain Supplement: Reproductive Details {Findings Domain}

To change this header/title, go to Notes Master IG 3.1.4 (Batch 1) 4/6/2017 http://www.cdisc.org/sdtm Public review Aug/Sep Exposure Domains Supplement : Clarification on variables Added / Updated Variables Variables proposed for Deprecation Variable clarifications, new variables and additional examples have been requested for the Exposure (EX) domain model. Clarified Definitions EX Domain: Recognized as a derived dataset Reflecting Subject Exposure: to protocol-specified study treatment(s), in protocol-specified unit(s) Reflecting collected information descriptive of doses not taken, not given or missed

To change this header/title, go to Notes Master IG 3.1.4 (Batch 1) 4/6/2017 http://www.cdisc.org/sdtm Public review Aug/Sep Exposure Domains Supplement : Clarification on variables EXVAMT: this variable has been identified for deprecation (see slide 12) Clarified Definitions EXDOSU: Values to reflect protocol-specified unit(s) Derivation from collected unit to protocol-specified unit may be required EXDOSE: Values to reflect the amount of active ingredient administered in protocol- specified unit EXDOSE = Number of units (e.g., TABLET) multiplied by Pharmaceutical Strength (active ingredient/unit), adjusted as-needed to protocol-specified unit. EXVAMT: Values to reflect the total amount of the prepared product (treatment + vehicle) administered

To change this header/title, go to Notes Master IG 3.1.4 (Batch 1) 4/6/2017 http://www.cdisc.org/sdtm Public review Aug/Sep Exposure Domains Supplement : Clarification on variables Added / Updated Variables Variables proposed for Deprecation EXOCCUR: Used to indicate whether a treatment occurred when information about the occurrence is solicited. EXOCCUR = ‘N’ when a treatment was not taken, not given, or missed. EXREASND Used in conjunction with EXOCCUR = ‘N’ to describe the reason the treatment administration was not taken, not given, or missed. Added / Updated Variables Added as permissible variables : EX domain EXOCCUR , EXREASND Definition Updates: • --DOSE: SDTM definition updated by adding –DOSTOT to the following sentence: ‘Not populated when --DOSTXT or --DOSTOT is populated.’ • --REASND: SDTM definition expanded; used in conjunction with --STAT value of ‘NOT DONE’ or --OCCUR value of ‘N’. .

To change this header/title, go to Notes Master IG 3.1.4 (Batch 1) 4/6/2017 http://www.cdisc.org/sdtm Public review Aug/Sep Added / Updated Variables (continued) Variables added to the Interventions General Observation Class New Interventions General Observation Class : -- MOOD Identify records as either ‘SCHEDULED’ or ‘PERFORMED’. --FAST Describe the fasting status at the time of the administration --METHOD Describe the method of administration --PSTRG Reflect the pharmaceutical strength of a treatment defined as the content of an active ingredient expressed quantitatively per dosage unit, per unit of volume, or per unit of weight, according to the pharmaceutical dose form --PSTRGU Reflect the associated unit of the pharmaceutical strength (e.g., mg/mL, mg/TABLET). --DOSTKN Represent the number of doses taken within an interval of time defined by --STDTC and --ENDTC or --DUR.

To change this header/title, go to Notes Master IG 3.1.4 (Batch 1) 4/6/2017 http://www.cdisc.org/sdtm Public review Aug/Sep Added / Updated Variables (continued) New General Observation Class : -- MTHOBS Represent the method of observation (e.g., OBSERVED, AUTOMATED DISPENSEMENT, SUBJECT DIARY, SUBJECT RECALL). If more than one value applies at the record-level, then --MTHOBS should be populated. --PTTMFL Permissible Timing variable to indicate if an intervention or event occurred at a point in time. If ‘Y’, then --ENDTC must be null. If null, then --ENDTC or --DUR should be populated

To change this header/title, go to Notes Master IG 3.1.4 (Batch 1) 4/6/2017 http://www.cdisc.org/sdtm Public review Aug/Sep Exposure Domains Supplement : Clarification on variables Added / Updated Variables Variables proposed for Deprecation Deprecation EXDOSTOT: was not intended to reflect a derived total daily dose (EXDOSE multiplied by EXDOSFRQ). Deprecation of this variable allows exposure dose representation to be in a single variable (i.e., EXDOSE) and eliminates inconsistent implementations of the variables across industry. (--DOSTOT will be deprecated (phased out) by the next (post v1.4 / v3.1.4) release ) TAETORD: Deleted from EX domain table; intended use in the domain was unclear. EXVAMT and EXVAMTU: With the addition of the EC domain model and use of FA to represent doses in alternative units, EXVAMT and EXVAMTU will be deprecated (phased out)

To change this header/title, go to Notes Master IG 3.1.4 (Batch 1) 4/6/2017 http://www.cdisc.org/sdtm Public review Aug/Sep Exposure Domains Supplement : New domain EC: Exposure as Collected EC Definition The Exposure as Collected domain model reflects protocol-specified study treatment administrations, as-collected. • EC should be used in all cases where collected exposure information cannot or should not be directly represented in EX or DA. For example, administrations collected in tablets but protocol-specified unit is mg, administrations collected in mL but protocol-specified unit is mg/kg, or administration details are collected as Drug Accountability. • If EC is an exact duplicate of EX, then EC is not necessary. • Exposure data are either represented in EX only or EC & EX or DA & EX.

To change this header/title, go to Notes Master IG 3.1.4 (Batch 1) 4/6/2017 http://www.cdisc.org/sdtm Public review Aug/Sep Domains introduced in IG 3.1.4 Immunogenicity Specimen Assessments (IS) : Definition: The Immunogenicity Specimen Assessments (IS) domain model is used for assessments, which determines whether a therapy provoked/caused/induced an immune response. For example, a vaccine is expected to induce an immune response to the therapeutic agent. Alternatively, a cellular therapy such as Erythropoiesis stimulating agents may induce an immune response that is not desired.

To change this header/title, go to Notes Master IG 3.1.4 (Batch 1) 4/6/2017 http://www.cdisc.org/sdtm Public review Aug/Sep Domains introduced in IG 3.1.4 Skin Responses (SR): Definition: The SR domain is a Findings About domain used to submit dermal responses to antigens. The method of assessment is typically a skin-prick test. Because a subject is typically exposed to many test materials at the same time. SROBJ is needed to represent the test material for each response record. .

To change this header/title, go to Notes Master IG 3.1.4 (Batch 1) 4/6/2017 http://www.cdisc.org/sdtm Public review Aug/Sep Domains introduced in IG 3.1.4 Reproductive Details (RD): Definition: This domain captures all Reproduction details captured in a study related to the subject in a FINDINGS domain Many of the findings proposed originated in legacy data conversions. Any new prospective reproductive tests need to be proposed with the CDISC Terminology Committee for formal inclusion All medication questions related to Reproduction Details should be mapped to the CM Interventions domain and categorized accordingly The current practice proposed for some Therapeutic Area’s is to populate a subject’s Birth Control Method in the Subject Characteristics (SC) domain. This was a practice based on previous SDTM alignment, with no specific Reproduction type domain existing. This finding should now be populated in the RD Findings domain as RDTESTCD=BCMETHOD and RDTEST=Birth Control Method to formalize the capture of this data value .

Part 2: Therapeutic Area Standards To change this title, go to Notes Master 4/6/2017 Part 2: Therapeutic Area Standards QBLM SDTM Forum

Therapeutic Specific Standards To change this header/title, go to Notes Master Therapeutic Specific Standards 4/6/2017 http://www.cdisc.org/therapeutic Draft Standards up for public review: Virology Draft Standards This is CDISC’s first attempt to develop submission standards for virology-focused trials. This document contains 5 proposed new SDTM domains, which includes basic information gene expression, human genetic variation, viral genetics and resistance data.

Therapeutic Specific Standards To change this header/title, go to Notes Master 4/6/2017 http://www.cdisc.org/sdtm Draft Standards up for public review: 2 core questionnaires for PD: National Institute of Nervous Disorder and Stroke (NINDS) core questionnaires Parkinson’s Disease Therapeutic Area User Guide This is a supplement to the SDTM User Guide and will be used with the SDTMIG. It will guide the user in the organization, structure and format of standard Parkinson’s disease clinical trial tabulation datasets. The PD User Guide includes the following in the review package: Assumptions and examples for using 10 existing SDTM standard domains implemented with PD specific common data elements. Draft domains and examples for 5 new SDTM draft domains that are important for PD and are included here to provide context for reviewers. Mapping and examples for the core questionnaires, along with their SDTM annotated CRF’s 

Therapeutic Specific Standards To change this header/title, go to Notes Master 4/6/2017 http://www.cdisc.org/sdtm Standards Available Pain therapeutic Area: The User Guide provides the background on the standards along with the specific Pain implementations of the MH domain, Questionnaire domain and Findings About domain. TB: Draft Domains are proposed standards that have been circulated for discussion in the CDISC user community but have not yet been included in a formal release of the SDTMIG, and thus may undergo further changes before being finalized. These draft domains will be released for public comment separately by the SDS team and incorporated in a future release of the SDTMIG, and are included here to provide context for users. Pain Therapeutic Area Standards User Guide, 19 Questionnaire Supplements 13 SDTM Annotated CRFs. (CT relevant to this PAIN User Guide is being been prepared through the CDISC Terminology Team and will be released as part of terminology package 12) Tuberculosis Therapeutic Area User Guide Includes 4 Draft Domains: Device in Use (DU) Morphology (MO) Microscopic Findings (MI) Skin Response (SR) (CT relevant to this TB User Guide is being been prepared through the

Therapeutic Specific Standards To change this header/title, go to Notes Master 4/6/2017 http://www.cdisc.org/therapeutic Standards Available Pain therapeutic Area: The User Guide provides the background on the standards along with the specific Pain implementations of the MH domain, Questionnaire domain and Findings About domain. Alzheimer’s disease/Mild Cognitive Impairment User Guide This document comprises version 1.0 of the Alzheimer's disease-specific Therapeutic Area Supplement User Guide ((SDTMUG-ALZHEIMERS v1.0).   This guide describes the explicit implementation of a subset of the existing and new SDTM safety domains. The Questionnaires selected for standardization in Alzheimer's disease studies The UG describes the assumptions and rules for the SDTM domains, a data example of specific domains and a SDTM mapping strategy as necessary The CDISC Questionnaire Terminology Team in the process of assessing copyright issues and developing controlled terminology for questionnaires.  The CDISC website will be updated on a regular basis to inform you of their progress