HIV Therapeutic Area User Guide v1.0

Therapeutic Area User Guide for HIV

Version 1.0 (Provisional)


Notes to Readers

  • This is the provisional version 1.0 of the Therapeutic Area User Guide for HIV.
  • This document is based on SDTM v1.7, SDTMIG v3.3 CDASH Model v1.0, CDASHIG v2.0, SDTMIG-AP v1.0, SDTMIG-MD v1.1, SDTMIG-PGx v1.0, ADaMIG v1.1 and ADaM v2.1.

Revision History

DateVersion
2019-01-181.0 Provisional

© 2019 Clinical Data Interchange Standards Consortium, Inc. All rights reserved.

1 Introduction

This Therapeutic Area Data Standards User Guide for HIV (TAUG-HIV) was developed under the Coalition for Accelerating Standards and Therapies (CFAST) initiative.

The purpose of the TAUG-HIV is to describe how to use Clinical Data Interchange Standards Consortium (CDISC) standards to represent data pertaining to HIV or data commonly collected in HIV trials. These include studies of both HIV treatment and HIV prevention, as well as studies that may include HIV-infected individuals.

1.1 How to Read this Document

  1. First, read the Study Data Tabulation Model (SDTM) Version 1.7, SDTM Implementation Guide (SDTMIG) Version 3.3, Clinical Data Acquisition Standards Harmonization (CDASH) Model Version 1.0, CDASH Implementation Guide (CDASHIG) Version 2.0, Analysis Data Model (ADaM) Version 2.1, and ADaM Implementation Guide (ADaMIG) Version 1.1. These standards are available at http://www.cdisc.org/.
  2. As needed, visit Section 1.3, CDASH Metadata and Annotated CRFs, of this guide for an explanation of how to read the annotated CRF.
  3. Read the SDTMIG for Associated Persons (SDTMIG-AP), SDTMIG for Pharmacogenomics/Genetics (SDTMIG-PGx), and SDTMIG for Medical Devices (SDTMIG-MD) to gain some familiarity with representing non-study subjects, genetics, and medical devices in the SDTM. These standards are available from: http://www.cdisc.org/.
  4. Read the Introduction to Therapeutic Area Standards (http://wiki.cdisc.org/x/SSy8AQ) and/or take CDISC's free training module, TA001 - Overview of Therapeutic Area User Guides (https://www.cdisc.org/education), to understand what to expect from a therapeutic area user guide.
  5. Read this guide all the way through (without skipping any sections) at least once.
  6. Finally, revisit any sections of particular interest.

Draft standards of interest to this document are listed at: Draft Standards of Interest to TAUG-HIV ( https://wiki.cdisc.org/x/OJ2FAg ).

For information and specifications for the content of data sets that should be submitted as part of the sponsor or applicant's application for drugs intended to treat HIV, refer to the FDA's HIV Technical Specifications Guidance: https://www.fda.gov/downloads/ForIndustry/DataStandards/StudyDataStandards/UCM603323.pdf.

All general caveats for the standards given in the Introduction to Therapeutic Area Standards (http://wiki.cdisc.org/x/SSy8AQ) apply to this document.

Implementers should always verify terminology shown in examples against current, published CDISC Controlled Terminology, available at the National Cancer Institute website (https://www.cancer.gov/research/resources/terminology/cdisc).

1.2 Organization of this Document

This document is divided into the following sections:

1.3 CDASH Metadata and Annotated CRFs

CDASH examples include both metadata tables and sample case report forms (CRFs). Each table of CDASH metadata corresponds to an example annotated CRF (aCRF), built directly from the metadata. The annotations show the variables associated with each field in the context of data collection (CDASH) and submission (SDTM). The color of the variable name denotes the applicable context. SDTMIG variable names are shown in RED. If the same variable name is used for both the SDTMIG variable and the CDASHIG variable, only the SDTMIG variable is shown. If the CDASHIG variable differs from the one defined in the SDTMIG, the CDASHIG variable is also shown in GRAY. Data collected but not submitted in SDTM-based datasets are denoted as. Not submitted

The following diagram illustrates how to interpret the annotations.

aCRF_2color

When viewing sample aCRFs, bear in mind that:

  • Sample CRFs are provided to illustrate data collection instruments. These examples are not meant to imply that any particular layout is preferable over another.
  • Example CRFs include annotations that refer to SDTM and CDASH data elements. Refer to these standards for more information about the use of these elements (https://www.cdisc.org/standards/foundational).
  • Most example CRFs do not include header information such as subject identifier and visit, where applicable. Information in these headers may be populated in a variety of ways depending on the data management system.
  • Sponsors are responsible for understanding and implementing CDISC Controlled Terminology (https://www.cancer.gov/research/resources/terminology/cdisc) where applicable.
  • CDASH variable names for denormalized variables are examples. Sponsors may use other conventions for creating denormalized CDASH names.
  • SDTM variable names separated by "/" indicate that either SDTM variable may be used when creating the SDTM datasets.

When viewing the CRF metadata, bear in mind that:

  • Some CDASH metadata attributes are not included.
  • Some non-CDASH metadata attributes necessary for rendering the CRF are included (eg, Hidden, Pre-specified Values, etc).

1.4 Known Issues

  • Non-standard variables: This document has adopted the practices outlined in the proposed SDTMIG Section 8.4.4, Alternative Representation of Non-Standard Variables (available in draft form at: http://wiki.cdisc.org/x/Ui68AQ). Accordingly, SDTM-based examples containing sample data requiring the use of a variable outside the standard set of variables included in the SDTM v1.7 are represented not with Supplemental Qualifier records, but with non-standard variables (NSVs) appended to the parent domain, followed by sample variable-level metadata for the NSVs.

    In order to avoid confusion between standard variables and NSVs, NSVs have been rendered visually distinct, as shown below, with white text on black in the header row, and separated from the standard variables by a small space. Metadata for the NSVs, from the define.xml file that would accompany the submission, are tabulated below the example. Only those attributes or elements that assist the example are included. (For more information on variable-level metadata in general, see the Define-XML Specifications found at: https://www.cdisc.org/standards/data-exchange/define-xml ). A list of all NSVs used in this document, and the variable-level metadata that might become normative for the NSVs should they be promoted to standard variables, is given in Appendix C, Non-Standard Variables.

  • Representation of prespecified findings: This guide shows an example in which prespecified findings from a pelvic exam are represented (see Section 4.2, Pelvic Examination). Within the CDISC community there is an ongoing discussion regarding the best way to represent prespecified findings. Historically, prespecified findings have been coordinated in the --TESTCD/--TEST variables (i.e., the prespecified target of interest is named in an indicator TEST, and the result is simply Y/N to indicate whether or not it was found). However, this can lead to a proliferation of controlled terms for these variables. Other options, including a new variable to represent the prespecified finding of interest (--RESTRG), are currently being explored. Previous therapeutic area user guides (TAUGs) have represented prespecified findings in the NSV --RESTRG. However, there has been a lack of consensus regarding this approach. Due to the lack of consensus, TAUGs will continue to coordinate prespecified findings in the --TESTCD/--TEST variables. This decision may change in the future.
  • Representation of subject characteristics collected more than once during a study: The concepts of gender identity and gestational age may be collected more than once during a study. Although these concepts are generally thought to belong in the Subject Characteristics (SC) domain, the SDTMIG v3.3 indicates that subject characteristics collected more than once should be represented in the Subject Status (SS) domain. However, representing gender identity in both SC and SS, depending on how often it is collected, conflicts with the principle that data should be consistently represented in only a single place. This issue was evaluated by the CDISC Global Governance Group, which decided that the assumptions of the SC domain should be modified to allow the representation of subject characteristics regardless of the number of times the characteristic is collected. This decision will be published in a future version of the SDTMIG. In this TAUG-HIV, Sections 3.2 (Representation of Gender Identity over Time) and 5.4 (Gestational Age) reflect this modeling decision.

  • Published gestational age controlled terminology: CDISC Controlled Terminology includes both RPTESTCD/RPTEST for EGESTAGE/Estimated Gestational Age and SCTESTCD/SCTEST for GSTABRTH/Gestational Age at Birth. Because gestational age is considered to be a subject characteristic of the infant, rather than a reproductive system finding, the published controlled terminology will be reviewed and updated. Section 5.4, Gestational Age, provides additional details.

  • Use of Device In Use (DU) to represent vaginal ring drug measurements:According to published controlled terminology the DU domain is "a domain for the findings for the values of measurements and settings that are intentionally set on a device when it is in use. These are characteristics that exist for the device, and have a specific setting for a use instance." However, there is ambiguity regarding whether or not the domain is intended to represent:

    • a domain for the findings for the values of (measurements and settings) that are intentionally set on a device when it is in use, or
    • a domain for the findings for the (values of measurements) and (settings that are intentionally set) on a device when it is in use.

    The Device Team has agreed that the second interpretation is what was originally intended when creating the domain. The definition and intended use will be clarified in the next version of the SDMTIG-MD. Because of this, the HIV Team felt it was appropriate to represent the vaginal ring drug measurements within DU (Section 6.2.1, Vaginal Ring).

  • Use of --RSDISC (Reason for Treatment Discontinuation) in the Device Exposure (DX) domain:In the vaginal ring example (Section 6.2.1, Vaginal Ring), the DXRSDISC variable is used to represent both the reason why each individual ring application ended and the overall reason for discontinuation of treatment with a vaginal ring.
  • Representation of the date of a particular medical history episode: The variable MHEVDTYP specifies the aspect of the medical condition or event by which MHSTDTC and/or the MHENDTC is defined. Current controlled terminology values are "DIAGNOSIS", "EPISODE", "EXACERBATION", and "SYMPTOM ONSET". When the date is for an episode or exacerbation, which episode or exacerbation (e.g., first, most recent, worst) must be specified. It has not yet been decided whether this information should be included in the value of MHEVDTYP (e.g., giving a value such as "MOST RECENT EPISODE"), or in a separate variable. In Section 4.1, Baseline Menstrual History, Example 1, a separate NSV (MHCRNORD) has been used to represent the fact that the date collected was for the most recent menstrual period.
  • Calculation of a single analysis value that is based on the data from more than 1 subject: The ADaM Basic Data Structure (BDS) class currently is designed to support subject-level analysis (as well as site-level analysis). However, grouping a number of subjects as an analysis unit has not been addressed. Example 1 in Section 8.3, Pregnancy Outcomes Analysis, proposes the variable USUBJGR1 (USUBJGRy as a generic variable) to allow for the grouping of subjects for analysis purposes. This allows for the calculation of a single analysis value that is based on the data from more than 1 subject. Because the ADOUTCOM dataset is summarized by family, based on the values across multiple subjects, a structure based on family and parameter is needed—which does not fit within the BDS definition. Therefore, it is proposed as an ADAM OTHER class of dataset.

2 Overview of HIV

Human immunodeficiency virus (HIV) causes a viral infection which, if not adequately controlled by treatment, may lead to acquired immunodeficiency syndrome (AIDS). HIV can weaken a person's immune system by reducing CD4+ T cells. AIDS is defined by the World Health Organization (WHO) as the occurrence of any 1 of more than 20 AIDS-defining clinical conditions, including opportunistic infections and HIV-related cancers.[1]The U.S. Centers for Disease Control and Prevention (CDC) definition is similar, but includes alternative criteria of a CD4+ cell count of fewer than 200 10^6/L or a CD4+ T cell percentage of total lymphocytes of less than 14%.[2] The 2 major types of HIV are HIV-1 and HIV-2. HIV-1 is the most common and most pathogenic. HIV-2 is less pathogenic and has been largely confined to Africa,although some cases have occurred in other parts of the world.

There are several populations that have a disproportionate burden of HIV. These groups include "men who have sex with men, transgender women in many settings and heterosexual men and women who have sexual partners with undiagnosed or untreated HIV infection".[3] Another population of interest is pregnant women with HIV. There are various approaches to preventing the mother-to-infant transmission of HIV. In HIV prevention studies involving pregnant women, infants will receive HIV testing and may receive antiretroviral therapy (ART) based on the mother's HIV status.

HIV treatment guidelines suggest a combination of antiretroviral (ARV) drugs to decrease the viral load below the levels of detection of sensitive HIV-RNA assays.[3,4] Antibody therapy may also be used to achieve this reduction in viral load. Current guidelines suggest lifelong treatment. Prevention of HIV in vulnerable populations includes the use of ARVs or treatment of potential sources (e.g., infected sexual partners, infected pregnant mothers to prevent perinatal transmission) prior to potential exposure to prevent transmission of HIV. Studies to develop vaccines for HIV have so far been unsuccessful. Vaccine trials are ongoing and may one day result in this being a viable option for prevention of HIV infection.[5,6]

Co-infections and complications of HIV-infected populations such as tuberculosis, hepatitis, and cardiovascular disease are also of interest. CDISC has published several therapeutic area user guides specifically for these indications. These guides can be found on the CDISC website (https://www.cdisc.org/standards/therapeutic-areas ).

3 Subject and Disease Characteristics

Information about subject and disease characteristics generally includes events and activities that have affected the subject prior to the study. In the TAUG-HIV, this includes:

3.1 Diagnosis of HIV

Diagnosing a subject with HIV requires an assay with a high degree of sensitivity and specificity. This is most easily achieved via a diagnostic algorithm that includes multiple redundant or complementary assays, as opposed to a single test.

The following concept map depicts a widely used algorithm for determining HIV status. Note that this algorithm does not apply to newborn infants of HIV-infected mothers.

Concept Map. HIV Diagnostic Algorithm

The following example illustrates a subject's progression through the diagnostic algorithm depicted in the concept map (second-stage confirmatory test results not shown).

Example

Because diagnosis of HIV involves a series of tests designed to detect antibodies to the virus, these findings are represented in the Immunogenicity Specimen Assessments (IS) domain. A final confirmatory test, which is designed to detect viral genetic material, is represented in the Microbiology Specimen (MB) domain. SPDEVID represents the device or kit used to obtain the individual results. The identifying details of these devices would be represented in the Device Identifiers (DI) dataset (example not shown).

The assays depicted in Rows 1-3 are antibody-only assays. Fourth-generation tests (combination tests that detect the presence of both HIV antibodies and HIV antigens) would be represented in the MB domain.

Rows 1-9:The combination of ISTESTCD / ISTEST and ISTSTDTL indicate that these tests are looking for the presence of the microbial-induced antibodies against the antigens identified in the non-standard variable ISBDAGNT.
Rows 1-3:Show the subject was tested with 3 separate enzyme immunoassay tests for HIV and tested positive on 2 and indeterminate on the other. These tests detect the presence of antibodies against HIV-1 and HIV-2, but do not differentiate which virus antibodies were detected.
Rows 4-9:Show the results from a confirmatory immunochromatographic assay that detects antibodies to specific antigens from both HIV-2 (Rows 4-5) and HIV-1 (Rows 6-9). Note that 2 distinct HIV-1 antibodies were detected (Rows 6 and 9).
Row 10:Shows the subject is HIV-2 negative according to the assay identified in SPDEVID. The sponsor has chosen to group this interpretation record via ISGRPID to the 2 records from the assay that are relevant to HIV-2 antibody detection.
Row 11:Shows the subject is HIV-1 positive according to the assay identified in SPDEVID. The sponsor has chosen to group this interpretation record via ISGRPID to the 4 records from the assay that are relevant to HIV-1 antibody detection.

is.xpt

RowSTUDYIDDOMAINUSUBJIDISSEQSPDEVIDISGRPIDISTESTCDISTESTISTSTDTLISORRESISSTRESCISSPECISMETHODVISITNUMVISITISDTC
ISBDAGNT
1ABCISABC-0031EIA01
MBABBinding Microbial-induced AntibodyDETECTIONDETECTEDDETECTEDBLOODEIA3WEEK 62017-05-22
HIV-1/2 Antigen
2ABCISABC-0032EIA02
MBABBinding Microbial-induced AntibodyDETECTIONINDETERMINATEINDETERMINATEBLOODEIA3WEEK 62017-05-22
HIV-1/2 Antigen
3ABCISABC-0033EIA03
MBABBinding Microbial-induced AntibodyDETECTIONDETECTEDDETECTEDBLOODEIA3WEEK 62017-05-22
HIV-1/2 Antigen
4ABCISABC-0034001051MBABBinding Microbial-induced AntibodyDETECTIONNOT DETECTEDNOT DETECTEDSERUMIMMUNOCHROMATOGRAPHY3WEEK 62017-05-22
HIV-2 GP36 Antigen
5ABCISABC-0035001051MBABBinding Microbial-induced AntibodyDETECTIONNOT DETECTEDNOT DETECTEDSERUMIMMUNOCHROMATOGRAPHY3WEEK 62017-05-22
HIV-2 GP140 Antigen
6ABCISABC-0036001052MBABBinding Microbial-induced AntibodyDETECTIONDETECTEDDETECTEDSERUMIMMUNOCHROMATOGRAPHY3WEEK 62017-05-22
HIV-1 P31 Antigen
7ABCISABC-0037001052MBABBinding Microbial-induced AntibodyDETECTIONNOT DETECTEDNOT DETECTEDSERUMIMMUNOCHROMATOGRAPHY3WEEK 62017-05-22
HIV-1 GP160 Antigen
8ABCISABC-0038001052MBABBinding Microbial-induced AntibodyDETECTIONNOT DETECTEDNOT DETECTEDSERUMIMMUNOCHROMATOGRAPHY3WEEK 62017-05-22
HIV-1 P24 Antigen
9ABCISABC-0039001052MBABBinding Microbial-induced AntibodyDETECTIONDETECTEDDETECTEDSERUMIMMUNOCHROMATOGRAPHY3WEEK 62017-05-22
HIV-1 GP41 Antigen
10ABCISABC-00310001051HIV2SRHIV-2 SeroreactivityINTERPRETATIONNEGATIVENEGATIVESERUMIMMUNOCHROMATOGRAPHY3WEEK 62017-05-22

11ABCISABC-00311001052HIV1SRHIV-1 SeroreactivityINTERPRETATIONPOSITIVEPOSITIVESERUMIMMUNOCHROMATOGRAPHY3WEEK 62017-05-22

IS NSV Metadata

The final confirmatory test detects the presence of viral RNA. Because this is not an antibody test, it is represented in MB rather than IS. This example shows that the subject was further tested for the presence of HIV-1 RNA using quantitative reverse transcriptase polymerase chain reaction. The target RNA was detected, confirming that the subject is HIV positive.

mb.xpt

RowSTUDYIDDOMAINUSUBJIDMBSEQMBTESTCDMBTESTMBTSTDTLMBORRESMBSTRESCMBSPECMBMETHODVISITNUMVISITMBDTC
1ABCMBABC-0031HIV1RNAHIV-1 RNADETECTIONDETECTEDDETECTEDBLOODQUANTITATIVE REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION3WEEK 62017-05-22

Because this event occurred during the course of the study, it is represented in the Clinical Events (CE) domain.

ce.xpt

RowSTUDYIDDOMAINUSUBJIDCESEQCETERMVISITNUMVISITCEDTC
1ABCCEABC-0031HIV test positive3WEEK 62017-05-22

There is no RELREC dataset included as part of this example. The sponsor could have used this dataset to create a link from the records in MB and IS, with the diagnosis record in CE. For more information on creating RELREC datastes, see SDTMIG Section 8.2, Relating Peer Records .

3.2 Representation of Gender Identity over Time

Transgender people are at high risk for HIV. Accurate capture and representation of gender identity in HIV prevention and treatment studies is important. Gender identity is the innermost concept of self as male, female, a blend of both, or neither. Gender is a spectrum, and not limited to just 2 possibilities. One's gender identity can be the same as the sex assigned at birth (cisgender) or different (transgender). A person may have a non-binary gender identity, meaning they do not identify strictly as male or female: They could identify as both, as neither, or as another gender entirely.[7,8,9]

Gender identity has traditionally been included in the Subject Characteristics (SC) domain. However, gender identity can be a fluid characteristic, especially in populations studied for HIV; thus it may be collected more than once during a study. A recent decision at CDISC allows subject characteristics collected as repeated measure to be included in SC. Further detail on this decision can be found in Section 1.4, Known Issues.

Because the terminology used to describe gender identity is evolving, CDISC has decided not to provide controlled terminology for potential values at this time. However, in order to populate the topic variable for SC consistently, a new SCTESTCD/SCTEST of "GENIDENT"/"Gender Identity" has been submitted to the CDISC Controlled Terminology Team.

In addition, the Tuberculosis Therapeutic Area User Guide v2.0 introduced the concept of "Sex Reported at Birth," which is also represented in the SC domain. The variable SEX in the Demographics (DM) domain is not well defined (sex of the subject) but is generally accepted to mean the self-reported sex of the subject. In support of this assumption, the CDASH Standard states that SEX is "the self-reported sex of the individual and/or is the clinician's assignment based on a physical examination. This is not to be confused with a genotypic determination of a subjects' chromosomally determined gender, but a less scientifically controlled method of visual determination that HL7 has defined as 'administrative sex.'" The concept of "Sex Reported at Birth" is intended to be used in cases where sex at birth differs from the subject's self-reported sex. However, sex and gender identity are complex issues that are only partially covered by the above concepts; further standards development work is required to adequately represent these concepts.

3.3 Risk Factors

Risk factors for contracting HIV include high-risk sexual behavior, intravenous drug use, prior sexually transmitted infections (STIs), and, for males, being uncircumcised.

Example 1 demonstrates a hypothetical CRF designed to capture the subject's history of HIV risk factors. The sponsor of this study chose to collect sexual behavior, sexually transmitted infections (STIs), intravenous drug use, and circumcision to assess the risk of HIV infection.

SDTM examples follow the aCRF.

This example refers to and makes use of the Environmental and Social Factors (ER) domain—a draft domain currently under discussion. As of the publication of this TAUG, the ER domain has no scheduled release date; the domain specification table can be found at https://wiki.cdisc.org/x/lIbIAQ.

Example

Annotated CRF: Risk Factors

This CRF collects information on e nvironmental and social risk factors. The specific STIs are collected on the Medical History CRF. In this example CRF, the following syntax was used to create denormalized CDASH variable names: SPONSOR DEFINED NAME_ROOT VARIABLE.

ERCAT Hidden/pre-populated
HIV RISK FACTORS
Indicate if the subject has engaged in sexual contact without a condom with same-sex partners at any point in their life, by checking Yes or No.Has the subject ever engaged in sexual contact without a condom with same-sex partners ?
UPSCSS_EROCCUR EROCCUR where ERTERM = "Sexual contact without a condom, same-sex partners"

<From NY codelist>

Indicate if the subject has engaged in sexual contact without a condom with opposite-sex partners at any point in their life, by checking Yes or No.Has the subject ever engaged in sexual contact without a condom with opposite-sex partners ?
UPSOP_EROCCUR EROCCUR where ERTERM = "Sexual contact without a condom, opposite-sex partners"

<From NY codelist>

Indicate if the subject has ever been diagnosed with an STI. If Yes, complete the STI Medical History CRF.Has the subject ever had a sexually transmitted infection (STI)?
PSTI_MHOCCUR MHOCCUR where MHTERM = "SEXUALLY TRANSMITTED INFECTIONS "

<From NY codelist>

Indicate if the subject has been or is an IV drug user.Has the subject ever been, or is now, an intravenous (IV) drug user?
IVU_EROCCUR EROCCUR where ERTERM = "Intravenous drug user"

<From NY codelist>

Indicate if the subject has ever been an uncircumcised male since becoming sexually active.Has the subject reported that he is, or that he has been, an uncircumcised male at any time since becoming sexually active?
UCM_EROCCUR EROCCUR where ERTERM = "Uncircumcised male"

<From NY codelist>

CRF Metadata
Order NumberTAUG ReferenceCDASHIG VariableCDASHIG Variable LabelQuestion TextPromptData TypeCRF Completion InstructionsMaps to the SDTMIG VariableSDTM Variable MappingControlled Terminology CodeList NameCRF Implementation NotesPermissible Valuesprespecified ValueQuery DisplayList StyleHidden
1TAUG-HIV v1.0ERCATEnvironment Risk CategoryWhat was the category of the environment risk?Environment Risk Factorstext
ERCAT



HIV RISK FACTORS

Y
2TAUG-HIV v1.0UPSCSS_EROCCUREnvironment Risk OccurrenceHas the subject ever engaged in sexual contact without a condom with same-sex partners ?Unprotected Same-SextextIndicate if the subject has engaged in sexual contact without a condom with same-sex partners at any point in their life, by checking Yes or No.EROCCUREROCCUR where ERTERM = "Sexual contact without a condom, same-sex partners"(NY)A sponsor may implement this as repeating rows or a table. The ERTERM would be included in a column and prespecified.Yes; No
question

3TAUG-HIV v1.0UPSOP_EROCCUREnvironment Risk OccurrenceHas the subject ever engaged in sexual contact without a condom with opposite-sex partners ?Unprotected Opposite-SextextIndicate if the subject has engaged in sexual contact without a condom with opposite-sex partners at any point in their life, by checking Yes or No.EROCCUREROCCUR where ERTERM = "Sexual contact without a condom, opposite-sex partners"(NY)A sponsor may implement this as repeating rows or a table. The ERTERM would be included in a column and prespecified.Yes; No



4TAUG-HIV v1.0PSTI_MHOCCUREnvironment Risk OccurrenceHas the subject ever had a sexually transmitted infection (STI)?STItextIndicate if the subject has ever been diagnosed with an STI. If Yes, complete the STI Medical History CRF.MHOCCURMHOCCUR where MHTERM = "SEXUALLY TRANSMITTED INFECTIONS "(NY)If a sponsor also collects the specific STI diagnosed on this CRF, these infections should be represented in the MH domain in accordance with the MH portion of the CRF.Yes; No



5TAUG-HIV v1.0IVU_EROCCUREnvironment Risk OccurrenceHas the subject ever been, or is now, an intravenous (IV) drug user?IV UsertextIndicate if the subject has been or is an IV drug user.EROCCUREROCCUR where ERTERM = "Intravenous drug user"(NY)
Yes; No



6TAUG-HIV v1.0UCM_EROCCUREnvironment Risk OccurrenceHas the subject reported that he is, or that he has been, an uncircumcised male at any time since becoming sexually active?Uncircumcised MaletextIndicate if the subject has ever been an uncircumcised male since becoming sexually active.EROCCUREROCCUR where ERTERM = "Uncircumcised male"(NY)
Yes; No



This Medical History CRF was used in this study to solicit the specific STI.

MHCAT Hidden/pre-populated
RISK FACTORS
MHSCAT Hidden/pre-populated
HISTORY OF STI
GONORRHEA_MHTERM MHTERM Hidden/pre-populated
GONORRHEA
Indicate if the subject has ever been diagnosed with gonorrhea.Has the subject ever had gonorrhea?
GONORRHEA_MHOCCUR MHOCCUR where MHTERM = "GONORRHEA"

<From NY codelist>

Record the start date of the medical event or condition.
GONORRHEA_MHSTDAT MHSTDTC
_________________
Indicate if the condition is ongoing at the time the history is collected.Is the event ongoing at the time of collection of this history?
GONORRHEA_MHONGO MHENRTPT where MHENTPT = Date of Collection

<From NY codelist>

Record the end date of the medical event or condition.
GONORRHEA_MHENDAT MHENDTC
_________________
CHLAMYDIA_MHTERM MHTERM Hidden/pre-populated
CHLAMYDIA
Indicate if the subject has ever been diagnosed with chlamydia.Has the subject ever had chlamydia?
CHLAMYDIA_MHOCCUR MHOCCUR where MHTERM = "CHLAMYDIA"

<From NY codelist>

Record the start date of the medical event or condition.
CHLAMYDIA_MHSTDAT MHSTDTC
_________________
Indicate if the condition is ongoing.Is the event ongoing at the time of collection of this history?
CHLAMYDIA_MHONGO MHENRTPT where MHENTPT = Date of Collection

<From NY codelist>

Record the end date of the medical event or condition.
CHLAMYDIA_MHENDAT MHENDTC
_________________
GENITAL_WARTS_MHTERM MHTERM Hidden/pre-populated
GENITAL WARTS
Indicate if the subject has ever been diagnosed with genital warts.Has the subject ever had genital warts?
GENITAL_WARTS_MHOCCUR MHOCCUR where MHTERM = "GENITAL WARTS"

<From NY codelist>

Record the start date of the medical event or condition.
GENITAL_WARTS_MHSTDAT MHSTDTC
_________________
Indicate if the condition is ongoing.Is the event ongoing at the time of collection of this history?
GENITAL_WARTS_MHONGO MHENRTPT where MHENTPT = Date of Collection

<From NY codelist>

Record the end date of the medical event or condition.
GENITAL_WARTS_MHENDAT MHENDTC
_________________
GENITAL_HERPES_MHTERM MHTERM Hidden/pre-populated
GENITAL HERPES
Indicate if the subject has ever been diagnosed with genital herpes.Has the subject ever had genital herpes?
GENITAL_HERPES_MHOCCUR MHOCCUR where MHTERM = "GENITAL HERPES"

<From NY codelist>

Record the start date of the medical event or condition.
GENITAL_HERPES_MHSTDAT MHSTDTC
_________________
Indicate if the condition is ongoing at the time of collection of this history.Is the event ongoing at the time of collection of this history?
GENITAL_HERPES_MHONGO MHENRTPT where MHENTPT = Date of Collection

<From NY codelist>

Record the end date of the medical event or condition.
GENITAL_HERPES_MHENDAT MHENDTC
_________________
SYPHILIS_MHTERM MHTERM Hidden/pre-populated
SYPHILIS
Indicate if the subject has ever been diagnosed with syphilis.Has the subject ever had syphilis?
SYPHILIS_MHOCCUR MHOCCUR where MHTERM = "SYPHILIS"

<From NY codelist>

Record the start date of the medical event or condition.
SYPHILIS_MHSTDAT MHSTDTC
_________________
Indicate if the condition is ongoing at the time of collection of this history.Is the event ongoing at the time of collection of this history?
SYPHILIS_MHONGO MHENRTPT where MHENTPT = Date of Collection

<From NY codelist>

Record the end date of the medical event or condition.
SYPHILIS_MHENDAT MHENDTC
_________________
HEPATITIS_B_MHTERM MHTERM Hidden/pre-populated
HEPATITIS B
Indicate if the subject has ever been diagnosed with hepatitis B.Has the subject ever had hepatitis B?
HEPATITIS_B_MHOCCUR MHOCCUR where MHTERM = "HEPATITIS B"

<From NY codelist>

Record the start date of the medical event or condition.
HEPATITIS_B_MHSTDAT MHSTDTC
_________________
Indicate if the condition is ongoing at the time of collection of this history.Is the event ongoing at the time of collection of this history?
HEPATITIS_B_MHONGO MHENRTPT where MHENTPT = Date of Collection

<From NY codelist>

Record the end date of the medical event or condition.
HEPATITIS_B_MHENDAT MHENDTC
_________________
CRF Metadata
Order NumberTAUG ReferenceCDASH VariableCDASHIG Variable LabelQuestion TextPromptTypeCRF Completion InstructionsInformation for SponsorsMaps to the SDTMIG VariableSDTM Variable MappingCRF Implementation NotesControlled Terminology CodeList NamePermissible Valuesprespecified ValueDisplayed QueryListHidden
1TAUG-HIV v1.0MHCATCategory for Medical HistoryWhat was the category of the medical history?Medical History CategorytextIndicate the category of the medical history event or condition.
MHCAT



RISK FACTORS

Y
2TAUG-HIV v1.0MHSCATSubcategory for Medical HistoryWhat was the subcategory of the medical history?Medical History SubcategorytextIndicate the subcategory of the medical history event or condition.
MHSCAT



HISTORY OF STI

Y
3TAUG-HIV v1.0GONORRHEA_MHTERMMedical History Event prespecifiedN/AGonorrheatextN/AMHPRESP would be prespecified as "Y" for all STI that are solicited.MHTERM
MHPRESP would be prespecified as "Y" for all STI that are solicited.

GONORRHEA

Y
4TAUG-HIV v1.0GONORRHEA_MHOCCURMedical History OccurrenceHas the subject ever had gonorrhea?GonorrheatextIndicate if the subject has ever been diagnosed with gonorrhea.A sponsor may also collect the specific STI diagnosed on this CRF. However, these infections should be represented in the MH domain.MHOCCURMHOCCUR where MHTERM = "GONORRHEA"A sponsor may also collect the specific STI diagnosed on this CRF. However, these infections should be represented in the MH domain.(NY)Yes;No

Radio Buttons
5TAUG-HIV v1.0GONORRHEA_MHSTDATMedical History Event Start DateWhat was the medical condition or event start date?Start DatetextRecord the start date of the medical event or condition.If the dates are not available, the sponsor may use reference timing variables as appropriate.MHSTDTC
If the dates are not available, the sponsor may use reference timing variables as appropriate.N/A




6TAUG-HIV v1.0GONORRHEA_MHONGOMedical History Event OngoingIs the event ongoing at the time of collection of this history?OngoingtextIndicate if the condition is ongoing at the time the history is collected.MHENTPT is the date of collection that informs MHENRTPT.MHENRFMHENRTPT where MHENTPT = Date of CollectionMHENTPT is the date of collection that informs MHENRTPT.(NY)Yes;No

Radio Buttons
7TAUG-HIV v1.0GONORRHEA_MHENDATMedical History Event End DateWhat was the medical condition or event end date?End DatetextRecord the end date of the medical event or condition.If the dates are not available, the sponsor may use reference timing variables as appropriate.MHENDTC
If the dates are not available, the sponsor may use reference timing variables as appropriate.N/A




8TAUG-HIV v1.0CHLAMYDIA_MHTERMMedical History Event prespecifiedN/AChlamydiatextN/AMHPRESP would be prespecified as "Y" for all STI that are solicited.MHTERM
MHPRESP would be prespecified as "Y" for all STI that are solicited.

CHLAMYDIA

Y
9TAUG-HIV v1.0CHLAMYDIA_MHOCCURMedical History OccurrenceHas the subject ever had chlamydia?ChlamydiatextIndicate if the subject has ever been diagnosed with chlamydia.A sponsor may also collect the specific STI diagnosed on this CRF. However, these infections should be represented in the MH domain.MHOCCURMHOCCUR where MHTERM = "CHLAMYDIA"A sponsor may also collect the specific STI diagnosed on this CRF. However, these infections should be represented in the MH domain.(NY)Yes;No

Radio Buttons
10TAUG-HIV v1.0CHLAMYDIA_MHSTDATMedical History Event Start DateWhat was the medical condition or event start date?Start DatetextRecord the start date of the medical event or condition.If the dates are not available, the sponsor may use reference timing variables as appropriate.MHSTDTC
If the dates are not available, the sponsor may use reference timing variables as appropriate.N/A




11TAUG-HIV v1.0CHLAMYDIA_MHONGOMedical History Event OngoingIs the event ongoing at the time of collection of this history?OngoingtextIndicate if the condition is ongoing.MHENTPT is the date of collection that informs MHENRTPT.MHENRTPTMHENRTPT where MHENTPT = Date of CollectionMHENTPT is the date of collection that informs MHENRTPT.(NY)Yes;No

Radio Buttons
12TAUG-HIV v1.0CHLAMYDIA_MHENDATMedical History Event End DateWhat was the medical condition or event end date?End DatetextRecord the end date of the medical event or condition.If the dates are not available, the sponsor may use reference timing variables as appropriate.MHENDTC
If the dates are not available, the sponsor may use reference timing variables as appropriate.N/A




13TAUG-HIV v1.0GENITAL_WARTS_MHTERMMedical History Event prespecifiedN/AGenital WartstextN/AMHPRESP would be prespecified as "Y" for all STI that are solicited.MHTERM
MHPRESP would be prespecified as "Y" for all STI that are solicited.

GENITAL WARTS

Y
14TAUG-HIV v1.0GENITAL_WARTS_MHOCCURMedical History OccurrenceHas the subject ever had genital warts?Genital WartstextIndicate if the subject has ever been diagnosed with genital warts.A sponsor may also collect the specific STI diagnosed on this CRF. However, these infections should be represented in the MH domain.MHOCCURMHOCCUR where MHTERM = "GENITAL WARTS"A sponsor may also collect the specific STI diagnosed on this CRF. However, these infections should be represented in the MH domain.(NY)Yes;No

Radio Buttons
15TAUG-HIV v1.0GENITAL_WARTS_MHSTDATMedical History Event Start DateWhat was the medical condition or event start date?Start DatetextRecord the start date of the medical event or condition.If the dates are not available, the sponsor may use reference timing variables as appropriate.MHSTDTC
If the dates are not available, the sponsor may use reference timing variables as appropriate.N/A




16TAUG-HIV v1.0GENITAL_WARTS_MHONGOMedical History Event OngoingIs the event ongoing at the time of collection of this history?OngoingtextIndicate if the condition is ongoing.If the end date is not available, the relative timing variables may be used. In this case, the relative timing variables ENRTPT and --ENTPT are used. MHENRTPT refer to the "time point anchor" described in --ENTPT.MHENRTPTMHENRTPT where MHENTPT = Date of CollectionIf the end date is not available, the relative timing variables may be used. In this case, the relative timing variables, ENRTPT and --ENTPT are used. MHENRTPT refer to the "time point anchor" described in --ENTPT.(NY)Yes;No

Radio Buttons
17TAUG-HIV v1.0GENITAL_WARTS_MHENDATMedical History Event End DateWhat was the medical condition or event end date?End DatetextRecord the end date of the medical event or condition.If the dates are not available, the sponsor may use reference timing variables as appropriate.MHENDTC
If the dates are not available, the sponsor may use reference timing variables as appropriate.N/A




18TAUG-HIV v1.0GENITAL_HERPES_MHTERMMedical History Event prespecifiedN/AGenital HerpestextN/AMHPRESP would be prespecified as "Y" for all STI that are solicited.MHTERM
MHPRESP would be prespecified as "Y" for all STI that are solicited.

GENITAL HERPES

Y
19TAUG-HIV v1.0GENITAL_HERPES_MHOCCURMedical History OccurrenceHas the subject ever had genital herpes?Genital HerpestextIndicate if the subject has ever been diagnosed with genital herpes.A sponsor may also collect the specific STI diagnosed on this CRF. However, these infections should be represented in the MH domain.MHOCCURMHOCCUR where MHTERM = "GENITAL HERPES"A sponsor may also collect the specific STI diagnosed on this CRF. However, these infections should be represented in the MH domain.(NY)Yes;No

Radio Buttons
20TAUG-HIV v1.0GENITAL_HERPES_MHSTDATMedical History Event Start DateWhat was the medical condition or event start date?Start DatetextRecord the start date of the medical event or condition.If the dates are not available, the sponsor may use reference timing variables as appropriate.MHSTDTC
If the dates are not available, the sponsor may use reference timing variables as appropriate.N/A




21TAUG-HIV v1.0GENITAL_HERPES_MHONGOMedical History Event OngoingIs the event ongoing at the time of collection of this history?OngoingtextIndicate if the condition is ongoing at the time of collection of this history.If the end date is not available,the relative timing variables may be used. In this case, the relative timing variables ENRTPT and --ENTPT are used. MHENRTPT refer to the "time point anchor" described in --ENTP.MHENRTPTMHENRTPT where MHENTPT = Date of CollectionIf the end date is not available,the relative timing variables may be used. In this case, the relative timing variables, ENRTPT and --ENTPT are used. MHENRTPT refer to the "time point anchor" described in --ENTP(NY)Yes;No

Radio Buttons
22TAUG-HIV v1.0GENITAL_HERPES_MHENDATMedical History Event End DateWhat was the medical condition or event end date?End DatetextRecord the end date of the medical event or condition.If the dates are not available, the sponsor may use reference timing variables as appropriate.MHENDTC
If the dates are not available, the sponsor may use reference timing variables as appropriate.N/A




23TAUG-HIV v1.0SYPHILIS_MHTERMMedical History Event prespecifiedN/ASyphilistextN/AMHPRESP would be prespecified as "Y" for all STI that are solicited.MHTERM
MHPRESP would be prespecified as "Y" for all STI that are solicited.

SYPHILIS

Y
24TAUG-HIV v1.0SYPHILIS_MHOCCURMedical History OccurrenceHas the subject ever had syphilis?SyphilistextIndicate if the subject has ever been diagnosed with syphilis.A sponsor may also collect the specific STI diagnosed on this CRF. However, these infections should be represented in the MH domain.MHOCCURMHOCCUR where MHTERM = "SYPHILIS"A sponsor may also collect the specific STI diagnosed on this CRF. However, these infections should be represented in the MH domain.(NY)Yes;No

Radio Buttons
25TAUG-HIV v1.0SYPHILIS_MHSTDATMedical History Event Start DateWhat was the medical condition or event start date?Start DatetextRecord the start date of the medical event or condition.If the dates are not available, the sponsor may use reference timing variables as appropriate.MHSTDTC
If the dates are not available, the sponsor may use reference timing variables as appropriate.N/A




26TAUG-HIV v1.0SYPHILIS_MHONGOMedical History Event OngoingIs the event ongoing at the time of collection of this history?
textIndicate if the condition is ongoing at the time of collection of this history.If the end date is not available, the relative timing variables may be used. In this case, the relative timing variables ENRTPT and --ENTPT are used. MHENRTPT refer to the "time point anchor" described in --ENTP.MHENRTPTMHENRTPT where MHENTPT = Date of CollectionIf the end date is not available,the relative timing variables may be used. In this case, the relative timing variables ENRTPT and --ENTPT are used. MHENRTPT refer to the "time point anchor" described in --ENTP.(NY)Yes;No

Radio Buttons
27TAUG-HIV v1.0SYPHILIS_MHENDATMedical History Event End DateWhat was the medical condition or event end date?End DatetextRecord the end date of the medical event or condition.If the dates are not available, the sponsor may use reference timing variables as appropriate.MHENDTC
If the dates are not available, the sponsor may use reference timing variables as appropriate.N/A




28TAUG-HIV v1.0HEPATITIS_B_MHTERMMedical History Event prespecifiedN/AHepatitis BtextN/AMHPRESP would be prespecified as "Y" for all STI that are solicited.MHTERM
MHPRESP would be prespecified as "Y" for all STI that are solicited.

HEPATITIS B

Y
29TAUG-HIV v1.0HEPATITIS_B_MHOCCURMedical History OccurrenceHas the subject ever had hepatitis B?Hepatitis BtextIndicate if the subject has ever been diagnosed with hepatitis B.A sponsor may also collect the specific STI diagnosed on this CRF. However, these infections should be represented in the MH domain.MHOCCURMHOCCUR where MHTERM = "HEPATITIS B"A sponsor may also collect the specific STI diagnosed on this CRF. However, these infections should be represented in the MH domain.(NY)Yes;No

Radio Buttons
30TAUG-HIV v1.0HEPATITIS_B_MHSTDATMedical History Event Start DateWhat was the medical condition or event start date?Start DatetextRecord the start date of the medical event or condition.If the dates are not available, the sponsor may use reference timing variables as appropriate.MHSTDTC
If the dates are not available, the sponsor may use reference timing variables as appropriate.N/A




31TAUG-HIV v1.0HEPATITIS_B_MHONGOMedical History Event OngoingIs the event ongoing at the time of collection of this history?
textIndicate if the condition is ongoing at the time of collection of this history.If the end date is not available,the relative timing variables may be used. In this case, the relative timing variables ENRTPT and --ENTPT are used. MHENRTPT refer to the "time point anchor" described in --ENTP.MHENRTPTMHENRTPT where MHENTPT = Date of CollectionIf the end date is not available,the relative timing variables may be used. In this case, the relative timing variables ENRTPT and --ENTPT are used. MHENRTPT refer to the "time point anchor" described in --ENTP.(NY)Yes;No

Radio Buttons
32TAUG-HIV v1.0HEPATITIS_B_MHENDATMedical History Event End DateWhat was the medical condition or event end date?End DatetextRecord the end date of the medical event or condition.If the dates are not available, the sponsor may use reference timing variables as appropriate.MHENDTC
If the dates are not available, the sponsor may use reference timing variables as appropriate.N/A




This example shows the results of a prespecified risk factors assessment for a subject enrolled in an HIV prevention study. This assessment is intended to be administered at the beginning of the study. Most of the items in the assessment pertain to any point in the subject's past, so EREVINTX is populated as "LIFETIME" for these items. One item pertains to the time since the subject became sexually active, and therefore has a value of "SINCE BECOMING SEXUALLY ACTIVE" in EREVINTX. In this example, the sponsor collected partial dates for the start date of the events .


Risk factors are represented in the Environmental and Social Factors (ER) domain. Because all of the risk factors queried for also exist as MedDRA terms, the sponsor chose to populate ERDECOD with the matching Preferred Term.

Rows 1-2:Show that the subject was asked about sexual contact without a condom. The subject indicated engagement in this risk-associated behavior with both same-sex and opposite-sex partners.
Row 3:Shows that the subject has never been an intravenous drug user.
Row 4:Shows that the subject has not been an uncircumcised male at any time since becoming sexually active.

er.xpt

RowSTUDYIDDOMAINUSUBJIDERSEQERTERMERDECODERCATERPRESPEROCCURERDTCEREVINTX
1ABCERABC-01-1011Sexual contact without a condom, same-sex partnersHigh-risk sexual behaviorHIV RISK FACTORSYY2017-10-02LIFETIME
2ABCERABC-01-1012Sexual contact without a condom, opposite-sex partnersHigh-risk sexual behaviorHIV RISK FACTORSYY2017-10-02LIFETIME
3ABCERABC-01-1013Intravenous drug userDrug abuserHIV RISK FACTORSYN2017-10-02LIFETIME
4ABCERABC-01-1014Uncircumcised maleUncircumcisedHIV RISK FACTORSYN2017-10-02SINCE BECOMING SEXUALLY ACTIVE

In this study, the risk factors assessment CRF triggered the investigator to review the subject's medical history for the occurrence of selected specific STIs. The sponsor allowed partial dates to be provided for the start dates of any events. The investigators were required to indicate if any event was ongoing at the time of data collection; however, the actual end date was allowed to be missing. In the example below, MHCAT and MHSCAT are used to indicate that these items were collected as part of a risk factors assessment.          

Row 1:Shows the subject responded "Yes" to the risk factors indicator question regarding past diagnosis of any STI.
Rows 2, 4:Show that the subject had past diagnoses of gonorrhea and genital warts. MHENRTPT and MHENTPT are used to indicate that the event ended before the date of collection of the STI history but the end date was not known.
Rows 3, 5-7:Show that the subject was asked about history of chlamydia, genital herpes, hepatitis B, and syphilis, but indicated never having contracted these diseases.

mh.xpt

RowSTUDYIDDOMAINUSUBJIDMHSEQMHTERMMHDECODMHCATMHSCATMHPRESPMHOCCURMHDTCMHSTDTCMHENDTCMHENRTPTMHENTPT
1ABCMHABC-01-1011SEXUALLY TRANSMITTED INFECTIONSexually transmitted diseaseHIV RISK FACTORSHISTORY OF STIYY2017-10-02

BEFORE2017-10-02
2ABCMHABC-01-1012GONORRHEAGonorrhoeaHIV RISK FACTORSHISTORY OF STIYY2017-10-022016-09-09
BEFORE2017-10-02
3ABCMHABC-01-1013CHLAMYDIAChlamydial infectionHIV RISK FACTORSHISTORY OF STIYN2017-10-02



4ABCMHABC-01-1014GENITAL WARTSAnogenital wartsHIV RISK FACTORSHISTORY OF STIYY2017-10-022013-04
BEFORE2017-10-02
5ABCMHABC-01-1015GENITAL HERPESGenital herpesHIV RISK FACTORSHISTORY OF STIYN2017-10-02



6ABCMHABC-01-1016SYPHILISSyphilisHIV RISK FACTORSHISTORY OF STIYN2017-10-02



7ABCMHABC-01-1017HEPATITIS BHepatitis BHIV RISK FACTORSHISTORY OF STIYN2017-10-02



3.4 Mode of Transmission

In HIV studies, it may be important to collect information about how the subject contracted the HIV virus (i.e., mode of disease transmission). At the broadest level, the mode of disease transmission can be categorized as either vertical transmission or horizontal transmission. Vertical transmission means that the virus is passed from mother to infant during pregnancy, birth, or breastfeeding. Horizontal transmission means that the virus is passed between individuals through activities such as sexual encounters and the sharing of IV needles.



As described below, HIV infections may be represented in either the Clinical Events (CE) domain or the Medical History (MH) domain, depending on the focus of the study. In either case, the mode of HIV transmission can be represented in the non-standard variable (NSV) --MODTR (Mode of Disease Transmission). If a study allows a subject to report more than 1 mode of transmission, --MODTR can be populated with "MULTIPLE". Additional NSVs can be added using the naming convention of --MODTR1 to --MODTRnto represent each mode of transmission reported. The level of granularity collected around the mode of transmission may vary by study. For example, a study may collect a category of mode of transmission such as "HORIZONTAL TRANSMISSION" or "VERTICAL TRANSMISSION". However, another study may collect a more granular mode of transmission that falls into 1 of these categories (e.g., "BLOOD TRANSFUSION", a type of horizontal transmission). Submission values can be found in the SDTM codelist, Mode of Disease Transmission (--MODTRN), and include:

HORIZONTAL TRANSMISSIONVERTICAL TRANSMISSION
SAME-SEX SEXUAL CONTACTINTRAUTERINE EXPOSURE
OPPOSITE-SEX SEXUAL CONTACTBREASTFEEDING
SEXUAL CONTACTLABOR AND DELIVERY
BLOOD TRANSFUSION
INJECTION NEEDLE REUSE
OCCUPATIONAL EXPOSURE

Example

This example shows the mode of transmission collected as part of a prevention study where subjects may contract the HIV virus during the course of the study. In this scenario, the mode of transmission is represented as a non-standard variable of the CE domain. The study allowed subjects to report more than 1 mode of transmission. Mode of transmission may also be collected in a treatment study. In that case, because the subject is already infected with HIV at the beginning of the study, mode of transmission could be represented as a MH NSV.

ce.xpt

RowSTUDYIDDOMAINUSUBJIDCESEQCETERMCEDECODCESTDTC
CEMODTRCEMODTR1CEMODTR2
1HIV-01CEHIV-01-0011HIV INFECTIONHIV infection2011-04-15
MULTIPLEOPPOSITE-SEX SEXUAL CONTACTINJECTION NEEDLE REUSE
2HIV-01CEHIV-01-0021HIV INFECTIONHIV infection2010-07-08
BLOOD TRANSFUSION

3HIV-01CEHIV-01-0031HIV INFECTIONHIV infection2010-06-05
MULTIPLEINJECTION NEEDLE REUSESAME-SEX SEXUAL CONTACT
4HIV-01CEHIV-01-0041HIV INFECTIONHIV infection2009-02-02
OCCUPATIONAL EXPOSURE

5HIV-01CEHIV-01-0051HIV INFECTIONHIV infection2009-05-11
UNKNOWN

CE NSV Metadata

4 Baseline Medical History and Physical Exams of Special Interest

This section contains examples and discussion on baseline menstrual history and pelvic examinations.

4.1 Baseline Menstrual History

HIV may cause more severe premenstrual symptoms for some women.[10] It is also possible that some women and girls living with or at risk for HIV, including those participating in clinical research for HIV/AIDS, do not menstruate. Reasons may include premenarche, menopause (natural or induced), long-acting contraceptives, and conditions that cause amenorrhea. Therefore, HIV/AIDS studies may need to collect more comprehensive data about the subject's gynecological assessments in order to place menstrual information within appropriate context.

Example 1 illustrates collecting information on premenstrual symptoms such as fatigue, cramps, headache, dysphoric disorder, pain, menstrual spotting, and diarrhea. Example 2 includes the number of days between menses and the range of usual bleeding days for the subject.

Example

This CRF was designed to collect menstrual history. General medical history was collected separately from this example. See Section 1.3, CDASH Metadata and Annotated CRFs, for explanation of annotations. In this example CRF, the following syntax was used to create denormalized CDASH variable names: <condition/event>_<root variable> (e.g., FATIGUE_MHOCCUR).

Baseline Menstrual History CRF

MHCAT Hidden/pre-populated
BASELINE MENSTRUAL HISTORY
MENSTRUAL_PERIOD_MHTERM MHTERM Hidden/pre-populated
Menstrual Period
Indicate if menses has occurred in the past 3 months by checking Yes or No.In the past 3 months, has the subject had her menses?
MENSTRUAL_PERIOD_MHOCCUR MHOCCUR where MHTERM = "Menstrual Period" and MHEVLINT = "-P3M"

<From NY codelist>

MHCRNORD NSV.MHCRNORD Hidden/pre-populated
MOST RECENT
Indicate the bleeding extent of the menstrual flow by choosing Light, Moderate, or Heavy.What was the bleeding extent of the most recent menses?
MHBLEXNT NSV.MHBLEXNT
Record the start date of the most recent menses.
MENSTRUAL_PERIOD_MHSTDAT MHSTDTC
_________________
Record the end date of the most recent menses.
MENSTRUAL_PERIOD_MHENDAT MHENDTC
_________________
MHSCAT Hidden/pre-populated
PREMENSTRUAL SYMPTOMS
PREMENSTRUAL_SYMPTOMS _MHTERM MHTERM Hidden/pre-populated
Premenstrual Symptoms
Indicate if premenstrual symptoms have occurred by checking Yes or No.Did the subject have premenstrual symptoms with the most recent menses?
PREMENSTRUAL_SYMPTOMS_MHOCCUR MHOCCUR where MHTERM = "Premenstrual Symptoms " and MHEVLINT = "-P3M"

<From NY codelist>

FATIGUE_MHTERM MHTERM Hidden/pre-populated
Fatigue
Indicate if fatigue has occurred by checking Yes or No.Did the subject have fatigue with the most recent menses?
FATIGUE_MHOCCUR MHOCCUR

<From NY codelist>

PREMENSTRUAL_CRAMPS_MHTERM MHTERM Hidden/pre-populated
Premenstrual Cramps
Indicate if premenstrual cramps have occurred by checking Yes or No.Did the subject have premenstrual cramps with the most recent menses?
PMCRAMPS_MHOCCUR MHOCCUR where MHTERM = "Premenstrual Cramps "

<From NY codelist>

HEADACHE_MHTERM MHTERM Hidden/pre-populated
Headache
Indicate if headache has occurred by checking Yes or No.Did the subject experience headache with the most recent menses?
HEADACHE_MHOCCUR MHOCCUR where MHTERM = "Headache "

<From NY codelist>

DYSPHORIC_DISORDER_MHTERM MHTERM Hidden/pre-populated
Dysphoric Disorder
Indicate if dysphoric disorder has occurred by checking Yes or No.Did the subject have dysphoric disorder with the most recent menses?
DYSPHORIC_DISORDER_MHOCCUR MHOCCUR where MHTERM = "Dysphoric Disorder "

<From NY codelist>

PAIN_MHTERM MHTERM Hidden/pre-populated
Pain
Indicate if pain has occurred by checking Yes or No.Did the subject have pain with the most recent menses?
PAIN_MHOCCUR MHOCCUR where MHTERM = "Pain "

<From NY codelist>

MENSTRUAL_SPOTTING_MHTERM MHTERM Hidden/pre-populated
Menstrual Spotting
Indicate if spotting has occurred by checking Yes or No.Did the subject experience menstrual spotting with the most recent menses?
MENSTRUAL_SPOTTING _MHOCCUR MHOCCUR where MHTERM = "Menstrual Spotting "

<From NY codelist>

List other symptoms, 1 per row or page.
OTHER_SYMPTOMS_MHTERM MHTERM where NSV.MHCRNORD = "MOST RECENT"
_________________
CRF Metadata
Order NumberTAUG ReferenceCDASH Variable NameCDASHIG Variable LabelQuestion TextPromptData TypeCRF Completion InstructionsMaps to the SDTMIG VariableSDTM Variable MappingCRF Implementation NotesControlled Terminology CodeList NamePermissible ValuesPre-specified ValueDisplayed QueryList StyleHidden
1TAUG-HIV v1.0MHCATCategory for Medical HistoryWhat is the category of the medical history?Medical History CategorytextIf collected on the CRF, the sponsor provides instructions to ensure the data is entered as intended.MHCAT
The sponsor may or may not preprint on the CRF the type of medical history being captured. If specific medical history (e.g., disease diagnosis) is captured in addition to the general medical history, it may be helpful to preprint the history type on the CRF. Regardless, MHCAT may be populated in the database as a derived field.N/A
BASELINE MENSTRUAL HISTORY

hidden
2TAUG-HIV v1.0MENSTRUAL_PERIOD_MHTERMMedical History Event Reported TermWhat is the verbatim term for the medical history condition/event?Medical History Event Reported TermtextN/AMHTERM

N/A
Menstrual Period

hidden
3TAUG-HIV v1.0MENSTRUAL_PERIOD_MHOCCURMedical History Event OccurrenceIn the past 3 months, has the subject had her menses?Menstrual Period OccurrencetextIndicate if menses has occurred in the past 3 months by checking Yes or No.MHOCCURMHOCCUR where MHTERM = "Menstrual Period" and MHEVLINT = "-P3M"
NYYes;No



4TAUG-HIV v1.0MHCRNORDChronological OrderWhat was the chronological order of the event?Medical History Event Chronological Ordertext
NSV.MHCRNORD
The sponsor populated MHCRNORD as "MOST RECENT" whenever MHOCCUR = "Y".N/A
MOST RECENT

hidden
5TAUG-HIV v1.0MHBLEXNTBleeding ExtentWhat was the bleeding extent of the most recent menses?Bleeding ExtenttextIndicate the bleeding extent of the menstrual flow by choosing Light, Moderate, or Heavy.NSV.MHBLEXNT


Light;Moderate;Heavy



6TAUG-HIV v1.0MENSTRUAL_PERIOD_MHSTDATMedical History Event Start DateWhat was the start date of the most recent menses?Start DatetextRecord the start date of the most recent menses.MHSTDTC
The sponsor may choose to capture a complete date or any variation thereof (e.g., month and year, year).N/A




7TAUG-HIV v1.0MENSTRUAL_PERIOD_MHENDATMedical History Event End DateWhat was the end date of the most recent menses?End DatetextRecord the end date of the most recent menses.MHENDTC
The sponsor may choose to capture a complete date or any variation thereof (e.g., month and year, year).N/A




8TAUG-HIV v1.0MHSCATSubcategory for Medical History EventWhat is the subcategory of the medical history?Medical History SubcategorytextIf collected on the CRF, the sponsor provides instructions to ensure the data is entered as intended.MHSCAT
This subcategory is only assigned to the records associated with premenstrual symptoms.N/A
PREMENSTRUAL SYMPTOMS

hidden
9TAUG-HIV v1.0PREMENSTRUAL_SYMPTOMS _MHTERMMedical History Event Reported TermWhat is the verbatim term for the medical history condition/event?Premenstrual SymptomstextN/AMHTERM

N/A
Premenstrual Symptoms

hidden
10TAUG-HIV v1.0PREMENSTRUAL_SYMPTOMS_MHOCCURMedical History Event OccurrenceDid the subject have premenstrual symptoms with the most recent menses?Premenstrual Symptoms OccurrencetextIndicate if premenstrual symptoms have occurred by checking Yes or No.MHOCCURMHOCCUR where MHTERM = "Premenstrual Symptoms " and MHEVLINT = "-P3M"
NYYes;No



11TAUG-HIV v1.0FATIGUE_MHTERMMedical History Event Reported TermWhat is the verbatim term for the medical history condition/event?Fa tiguetextN/AMHTERM

N/A
Fatigue

hidden
12TAUG-HIV v1.0FATIGUE_MHOCCURMedical History Event OccurrenceDid the subject have fatigue with the most recent menses?Fatigue OccurrencetextIndicate if fatigue has occurred by checking Yes or No.MHOCCUR

NYYes;No



13TAUG-HIV v1.0PREMENSTRUAL_CRAMPS_MHTERMMedical History Event Reported TermWhat is the verbatim term for the medical history condition/event?Premenstrual CrampstextN/AMHTERM

N/A
Premenstrual Cramps

hidden
14TAUG-HIV v1.0PMCRAMPS_MHOCCURMedical History Event OccurrenceDid the subject have premenstrual cramps with the most recent menses?Premenstrual Cramps OccurrencetextIndicate if premenstrual cramps have occurred by checking Yes or No.MHOCCURMHOCCUR where MHTERM = "Premenstrual Cramps "
NYYes;No



15TAUG-HIV v1.0HEADACHE_MHTERMMedical History Event Reported TermWhat is the verbatim term for the medical history condition/event?HeadachetextN/AMHTERM

N/A
Headache

hidden
16TAUG-HIV v1.0HEADACHE_MHOCCURMedical History Event OccurrenceDid the subject experience headache with the most recent menses?Headache OccurrencetextIndicate if headache has occurred by checking Yes or No.MHOCCURMHOCCUR where MHTERM = "Headache "
NYYes;No



17TAUG-HIV v1.0DYSPHORIC_DISORDER_MHTERMMedical History Event Reported TermWhat is the verbatim term for the medical history condition/event?Dysphoric DisordertextN/AMHTERM

N/A
Dysphoric Disorder

hidden
18TAUG-HIV v1.0DYSPHORIC_DISORDER_MHOCCURMedical History Event OccurrenceDid the subject have dysphoric disorder with the most recent menses?Dysphoric Disorder OccurrencetextIndicate if dysphoric disorder has occurred by checking Yes or No.MHOCCURMHOCCUR where MHTERM = "Dysphoric Disorder "
NYYes;No



19TAUG-HIV v1.0PAIN_MHTERMMedical History Event Reported TermWhat is the verbatim term for the medical history condition/event?PaintextN/AMHTERM

N/A
Pain

hidden
20TAUG-HIV v1.0PAIN_MHOCCURMedical History Event OccurrenceDid the subject have pain with the most recent menses?Pain OccurrencetextIndicate if pain has occurred by checking Yes or No.MHOCCURMHOCCUR where MHTERM = "Pain "
NYYes;No



21TAUG-HIV v1.0MENSTRUAL_SPOTTING_MHTERMMedical History Event Reported TermWhat is the verbatim term for the medical history condition/event?Menstrual SpottingtextN/AMHTERM

N/A
Menstrual Spotting

hidden
22TAUG-HIV v1.0MENSTRUAL_SPOTTING _MHOCCURMedical History Event OccurrenceDid the subject experience menstrual spotting with the most recent menses?Menstrual Spotting OccurencetextIndicate if spotting has occurred by checking Yes or No.MHOCCURMHOCCUR where MHTERM = "Menstrual Spotting "
NYYes;No



23TAUG-HIV v1.0OTHER_SYMPTOMS_MHTERMMedical History Event Reported TermList any other premenstrual symptoms that the subject experienced, associated with the most recent menses.Other SymptomstextList other symptoms, 1 per row or page.MHTERMMHTERM where NSV.MHCRNORD = "MOST RECENT"
N/A




Row 1:Shows that the subject experienced a menstrual period within the last 3 months with the bleeding extent characterized as "moderate" (MHBLEXNT="MODERATE"). MHPRESP and MHOCCUR are equal to "Y" because the event has occurred and was prespecified on the CRF.
Rows 2-8:Show that the subject experienced premenstrual symptoms, in general, as well as specific symptoms pre-specified on the CRF. MHSCAT="PREMENSTRUAL SYMPTOMS" and MHGRPID="1" and has been used to group the subject's premenstrual symptoms. The variables MHSTDTC and MHENDTC were not collected. The timing of these events is represented indirectly by the combination of the date of collection, MHDTC, with MHCRNORD="MOST RECENT".
Row 9:Shows a record for a write-in premenstrual symptom recorded in the "Other, Specify" space. Because this event was not prespecified, MHOCCUR and MHPRESP are null.

mh.xpt

RowSTUDYIDDOMAINUSUBJIDMHSEQMHGRPIDMHTERMMHCATMHSCATMHPRESPMHOCCURMHDTCMHSTDTCMHENDTCMHEVLINT
MHCRNORDMHBLEXNT
1ABCMHABC-00111Menstrual PeriodBASELINE MENSTRUAL HISTORY
YY2016-06-012016-05-222016-05-27-P3M
MOST RECENTMODERATE
2ABCMHABC-00121Premenstrual SymptomsBASELINE MENSTRUAL HISTORYPREMENSTRUAL SYMPTOMSYY2016-06-01



MOST RECENT
3ABCMHABC-00131FatigueBASELINE MENSTRUAL HISTORYPREMENSTRUAL SYMPTOMSYY2016-06-01



MOST RECENT
4ABCMHABC-00141Premenstrual CrampsBASELINE MENSTRUAL HISTORYPREMENSTRUAL SYMPTOMSYY2016-06-01



MOST RECENT
5ABCMHABC-00151HeadacheBASELINE MENSTRUAL HISTORYPREMENSTRUAL SYMPTOMSYY2016-06-01



MOST RECENT
6ABCMHABC-00161Dysphoric DisorderBASELINE MENSTRUAL HISTORYPREMENSTRUAL SYMPTOMSYY2016-06-01



MOST RECENT
7ABCMHABC-00171PainBASELINE MENSTRUAL HISTORYPREMENSTRUAL SYMPTOMSYY2016-06-01



MOST RECENT
8ABCMHABC-00181Menstrual SpottingBASELINE MENSTRUAL HISTORYPREMENSTRUAL SYMPTOMSYY2016-06-01



MOST RECENT
9ABCMHABC-00191DiarrheaBASELINE MENSTRUAL HISTORYPREMENSTRUAL SYMPTOMS

2016-06-01



MOST RECENT

MH NSV Metadata

Example

HIV may alter the duration, frequency, or bleeding extent of a woman's menstrual cycle. It may be important to collect these data during an HIV study. See Section 1.3, CDASH Metadata and Annotated CRFs, for explanation of annotations. In this example CRF, the following syntax was used to create denormalized CDASH variable names: <condition/event>_<root variable> (e.g., MENARAGE_RPORRES ).

Baseline Menstrual History CRF 2

Record the date when the menstrual history was collected, using this format: DD-MON-YYYY.
RPDAT RPDTC
_________________
RPCAT Hidden/pre-populated
BASELINE MENSTRUAL HISTORY
MENARAGE_RPTEST RPTEST Hidden/pre-populated
Menarche Age

<From RPTEST codelist>

Record the menarche age for the subject.
MENARAGE_RPORRES RPORRES where RPTESTCD = "MENARAGE"
_____
MENARAGE_RPORRESU RPORRESU where RPTESTCD = "MENARAGE" Hidden/pre-populated
YEARS

<From AGEU codelist>

NUMBTWMN_RPTEST RPTEST Hidden/pre-populated
Usual Number of Days Between Menses

<From RPTEST codelist>

Record the subject's u sual number of days between menses .
NUMBTWMN _RPORRES RPORRES where RPTESTCD = "NUMBTWMN"
_____
NUMBTWMN _RPORRESU RPORRESU where RPTESTCD = " NUMBTWMN " Hidden/pre-populated
DAYS

<From UNIT codelist>

NUMBLMIN_RPTEST RPTEST Hidden/pre-populated
Usual Minimum Number of Bleeding Days

<From RPTEST codelist>

Record the usual minimum number of bleeding days for the subject.
NUMBLMIN _RPORRES RPORRES where RPTESTCD = " NUMBLMIN "
_____
NUMBLMIN _RPORRESU RPORRESU where RPTESTCD = " NUMBLMIN " Hidden/pre-populated
DAYS

<From UNIT codelist>

NUMBLMAX_RPTEST RPTEST Hidden/pre-populated
Usual Maximum Number of Bleeding Days

<From RPTEST codelist>

Record the usual maximum number of bleeding days for the subject.
NUMBLMAX _RPORRES RPORRES where RPTESTCD = " NUMBLMAX "
_____
NUMBLMAX _RPORRESU RPORRESU where RPTESTCD = " NUMBLMAX " Hidden/pre-populated
DAYS

<From UNIT codelist>

CRF Metadata
Order NumberTAUG ReferenceCDASH VariableCDASHIG Variable LabelQuestion TextPromptField TypeCase Report Form Completion InstructionsInformation for SponsorsMaps to the SDTMIG VariableSDTM Variable MappingControlled Terminology CodeList NameCRF Implementation NotesPermissible ValuesPre-specified ValueDisplayed QueryList StyleHidden?
1TAUG-HIV v1.0RPDATDate of Reproductive System FindingWhat was the date when the menstrual history was collected?Menstrual History Collection DatetextRecord the date when the menstrual history was collected, using this format: DD-MON-YYYY.
RPDTC
N/A





2TAUG-HIV v1.0RPCATCategory for Reproductive System FindingsWhat was the category of the reproductive system?Reproductive System CategorytextN/A
RPCAT
N/A

BASELINE MENSTRUAL HISTORY

hidden
3TAUG-HIV v1.0MENARAGE_RPTESTReproductive System Findings Test NameWhat was Reproductive System Findings Test Name ?Reproductive Finding NametextN/A
RPTEST
(RPTEST)The SDTMIG variable RPTESTCD may be determined from the value collected in RPTEST
Menarche Age

hidden
4TAUG-HIV v1.0MENARAGE_RPORRESReproductive System Findings ResultWhat was the subject's menarche age?ResultintegerRecord the menarche age for the subject.
RPORRESRPORRES where RPTESTCD = "MENARAGE"N/A





5TAUG-HIV v1.0MENARAGE_RPORRESUReproductive System Findings Result UnitUnitUnittextRecord or select the original unit in which these data were collected, if not preprinted on CRF.
RPORRESURPORRESU where RPTESTCD = "MENARAGE"(AGEU)

YEARS

hidden
6TAUG-HIV v1.0NUMBTWMN_RPTESTReproductive System Findings Test NameWhat was Reproductive System Findings Test Name ?Reproductive Finding NametextN/A
RPTESTRPTEST(RPTEST)The SDTMIG variable RPTESTCD may be determined from the value collected in RPTEST
Usual Number of Days Between Menses

hidden
7TAUG-HIV v1.0NUMBTWMN _RPORRESReproductive System Findings ResultWhat is the subject's u sual number of days between menses ?ResultintegerRecord the subject's u sual number of days between menses .
RPORRESRPORRES where RPTESTCD = "NUMBTWMN"N/A





8TAUG-HIV v1.0NUMBTWMN _RPORRESUReproductive System Findings Result UnitUnitUnittextRecord or select the original unit in which these data were collected, if not preprinted on CRF.
RPORRESURPORRESU where RPTESTCD = " NUMBTWMN "(UNIT)

DAYS

hidden
9TAUG-HIV v1.0NUMBLMIN_RPTESTReproductive System Findings Test NameWhat was Reproductive System Findings Test Name ?Reproductive Finding NametextN/A
RPTESTRPTEST(RPTEST)The SDTMIG variable RPTESTCD may be determined from the value collected in RPTEST
Usual Minimum Number of Bleeding Days

hidden
10TAUG-HIV v1.0NUMBLMIN _RPORRESReproductive System Findings ResultWhat is the usual minimum number of bleeding days for the subject?ResultintegerRecord the usual minimum number of bleeding days for the subject.
RPORRESRPORRES where RPTESTCD = " NUMBLMIN "N/A





11TAUG-HIV v1.0NUMBLMIN _RPORRESUReproductive System Findings Result UnitUnitUnittextRecord or select the original unit in which these data were collected, if not preprinted on CRF.
RPORRESURPORRESU where RPTESTCD = " NUMBLMIN "(UNIT)

DAYS

hidden
12TAUG-HIV v1.0NUMBLMAX_RPTESTReproductive System Findings Test NameWhat was Reproductive System Findings Test Name ?Reproductive Finding NametextN/A
RPTESTRPTEST(RPTEST)The SDTMIG variable RPTESTCD may be determined from the value collected in RPTEST
Usual Maximum Number of Bleeding Days

hidden
13TAUG-HIV v1.0NUMBLMAX _RPORRESReproductive System Findings ResultWhat is the usual maximum number of bleeding days for the subject?ResultintegerRecord the usual maximum number of bleeding days for the subject.
RPORRESRPORRES where RPTESTCD = " NUMBLMAX "N/A





14TAUG-HIV v1.0NUMBLMAX _RPORRESUReproductive System Findings Result UnitUnitUnittextRecord or select the original unit in which these data were collected, if not preprinted on CRF.
RPORRESURPORRESU where RPTESTCD = " NUMBLMAX "(UNIT)

DAYS

hidden
Row 1:Shows that the subject began menstruating at the age of 13 years .
Rows 2-4:Show various details regarding the subject's usual menstrual cycle, including number of days between menses and the range of the usual bleeding days.

rp.xpt

RowSTUDYIDDOMAINUSUBJIDRPSEQRPTESTCDRPTESTRPCATRPORRESRPORRESURPSTRESCRPSTRESNRPSTRESUVISITNUMVISITRPDTC
1ABCRPABC-0011MENARAGEMenarche AgeBASELINE MENSTRUAL HISTORY13YEARS1313YEARS1SCREENING2016-06-01
2ABCRPABC-0012NUMBTWMNUsual Number of Days Between MensesBASELINE MENSTRUAL HISTORY28DAYS2828DAYS1SCREENING2016-06-01
3ABCRPABC-0013NUMBLMINUsual Number of Bleeding Days, MinBASELINE MENSTRUAL HISTORY4DAYS44DAYS1SCREENING2016-06-01
4ABCRPABC-0014NUMBLMAXUsual Number of Bleeding Days, MaxBASELINE MENSTRUAL HISTORY7DAYS77DAYS1SCREENING2016-06-01

4.2 Pelvic Examination

During a pelvic examination, an investigator may check for prespecified abnormalities. When this occurs, the prespecified finding of interest is represented in RPTESTCD/RPTEST. The value in the variable RPORRES indicates whether the prespecified finding of interest was observed. Example 1 shows the representation of data from a prespecified pelvic exam for a single subject.

Example

In this example, the mother was a study subject. If the mother were an associated person, the data would be represented in the APMH domain and the dataset would include APID, RSUBJID, and SREL, rather than USUBID.

rp.xpt

RowSTUDYIDDOMAINUSUBJIDRPSEQRPTESTCDRPTESTRPCATRPORRESRPSTRESCRPLOCVISITNUMVISITRPDTC
1ABCRPABC-0011EDEMAINDEdema IndicatorPELVIC EXAM FINDINGSYYVULVA1SCREENING2016-02-08
2ABCRPABC-0012ERYTHINDErythema IndicatorPELVIC EXAM FINDINGSYYVULVA1SCREENING2016-02-08
3ABCRPABC-0013RASHINDRash IndicatorPELVIC EXAM FINDINGSNNVULVA1SCREENING2016-02-08
4ABCRPABC-0014TENDINDTenderness IndicatorPELVIC EXAM FINDINGSYYVULVA1SCREENING2016-02-08
5ABCRPABC-0015SKGLAINDSkene's Gland Abnormality IndicatorPELVIC EXAM FINDINGSNNVULVA1SCREENING2016-02-08
6ABCRPABC-0016BTHGLINDBartholin's Gland Abnormality IndicatorPELVIC EXAM FINDINGSNNVULVA1SCREENING2016-02-08
7ABCRPABC-0017ULCERINDUlcer IndicatorPELVIC EXAM FINDINGSYYVULVA1SCREENING2016-02-08
8ABCRPABC-0018BLISTINDBlister IndicatorPELVIC EXAM FINDINGSYYVULVA1SCREENING2016-02-08
9ABCRPABC-0019PUSTINDPustule IndicatorPELVIC EXAM FINDINGSNNVULVA1SCREENING2016-02-08
10ABCRPABC-00110PEELINDPeeling IndicatorPELVIC EXAM FINDINGSYYVULVA1SCREENING2016-02-08
11ABCRPABC-00111ECCHYINDEcchymosis IndicatorPELVIC EXAM FINDINGSNNVULVA1SCREENING2016-02-08
12ABCRPABC-00112EDEMAINDEdema IndicatorPELVIC EXAM FINDINGSYYCERVIX UTERI1SCREENING2016-02-08
13ABCRPABC-00113ERYTHINDErythema IndicatorPELVIC EXAM FINDINGSYYCERVIX UTERI1SCREENING2016-02-08
14ABCRPABC-00114MASSINDMass IndicatorPELVIC EXAM FINDINGSNNCERVIX UTERI1SCREENING2016-02-08
15ABCRPABC-00115MTENDINDMotion Tenderness IndicatorPELVIC EXAM FINDINGSNNCERVIX UTERI1SCREENING2016-02-08
16ABCRPABC-00116DSCHGINDDischarge IndicatorPELVIC EXAM FINDINGSYYCERVIX UTERI1SCREENING2016-02-08
17ABCRPABC-00117ULCERINDUlcer IndicatorPELVIC EXAM FINDINGSNNCERVIX UTERI1SCREENING2016-02-08
18ABCRPABC-00118BLISTINDBlister IndicatorPELVIC EXAM FINDINGSYYCERVIX UTERI1SCREENING2016-02-08
19ABCRPABC-00119PUSTINDPustule IndicatorPELVIC EXAM FINDINGSNNCERVIX UTERI1SCREENING2016-02-08
20ABCRPABC-00120PEELINDPeeling IndicatorPELVIC EXAM FINDINGSYYCERVIX UTERI1SCREENING2016-02-08
21ABCRPABC-00121ECCHYINDEcchymosis IndicatorPELVIC EXAM FINDINGSNNCERVIX UTERI1SCREENING2016-02-08
22ABCRPABC-00122BLEEDINDAbnormal Bleeding IndicatorPELVIC EXAM FINDINGSNNFEMALE GENITALIA1SCREENING2016-02-08

5 Mother-Infant Pairs in HIV Studies

Given the high burden of HIV infection among women of childbearing potential, particularly in low- and middle-income settings, the study of HIV treatment and prevention in HIV-infected pregnant women and their infants is of high priority. When a subject is pregnant or becomes pregnant, it is important to track pregnancy outcomes and it may be necessary to collect both prenatal and postnatal data on the infant pertaining to overall health and HIV status.

In studies that collect perinatal data, the term used to describe the child changes over time, from fetus to newborn (or neonate) to infant. Within particular examples where the child is at a particular stage, the appropriate term will be used, according to definitions in Appendix B, Glossary and Abbreviations. Statements in this document that apply to multiple stages use the term infant.

In SDTM-based datasets, data about persons who are not study subjects (associated persons) are represented differently from data about study subjects. This means that representation of data about mothers and infants depends on whether they are study subjects or associated persons—which, in turn, depends on the study design and protocol. This section covers the representation of data collected about mothers and infants and the representation of the relationship between mother and infant in studies where one or the other or both are study subjects.

5.1 Studies Involving Mother-Infant Data

The roles that mothers and infants play in a study determine how pregnancy and perinatal data are represented in the SDTM. This TAUG-HIV includes examples that illustrate data in one of 3 categories of study: those that enroll women of childbearing potential, studies of mothers and infants, and studies of infants.

Studies that Enroll Women of Childbearing Potential

If a woman of childbearing potential becomes pregnant during a study, the protocol may call for collection of data about the pregnancy and minimal data about the infant(s). In such a study, the infant is unlikely to be treated as a study subject, but rather as an associated person or a non-study subject. Any data about the infant would be represented in an associated persons (AP) dataset, as described in the SDTMIG-AP.

An associated person is given an associated person identifier (APID), rather than a unique subject identifier (USUBJID). AP datasets include the APID, the USUBJID of the study subject with whom they are associated (RSUBJID), and a variable (SREL) that describes the relationship of the associated person to the study subject. SREL would be a value such as "CHILD, BIOLOGICAL" for infants of mothers in a study in this category.

Studies of Mothers and Infants

Some studies enroll pregnant women and treat a mother and her infant(s) as study subjects. In this case, each person has a unique subject identifier (USUBJID). Relationships between study subjects can be represented in the Related Subjects dataset (RELSUB).

Studies of Infants

There are occasional studies of neonates which collect data about mothers, but in which the mothers are associated persons, rather than study subjects. Maternal data would be represented in AP domains.

One example of such a study is a pharmacokinetics (PK) study in infants. In this study, pregnant women were recruited so that the treatment of eligible infants could begin shortly after birth. Mothers in this study were considered associated persons, and maternal data collected during the prenatal period were represented as maternal data in AP datasets. These data included pregnancy-related events and data about medications taken during pregnancy and lactation.

5.2 Identifiers and Relationships for Mother-Infant Pairs

The mother-infant relationship is represented in the SDTM in a RELSUB dataset if both mother and the infant are study subjects, and in an Associated Persons Related Subjects (APRELSUB) dataset if only 1 is a study subject. The APRELSUB dataset is not necessary unless there are associated persons who have either relationships with multiple study subjects or multiple relationships with the same study subject. However, the APRELSUB dataset can be helpful even when not required, as a single dataset that shows all relationships of associated persons to study subjects.

Because multiple gestations during a single pregnancy increase the complexity of data modeling, many of the examples shown in this section are based on a mother who is pregnant with or has given birth to twins. In the examples for scenarios in which the mother is a study subject, the infant identifiers are shown as the mother's study identifier with the letter "A" or "B" appended. In the scenario where the mother is an associated person, the mother's identifier is based on the identifier of an infant.

When the mother is the study subject and the infant is an associated person, the relationship of the infant to the mother is represented in each record in an AP dataset, since AP datasets include the variables RSUBJID (Related Subject Identifier) and SREL (Subject Relationship). The relationship can also be represented in the APRELSUB dataset. Relationships are described as the relationship of the associated person to the study subject, so only 1 record is required for each relationship.

Example

This example is for a study in which mothers were study subjects and infants were associated persons. In this example, a mother gave birth to twins and the sponsor assigned associated person identifiers (APIDs) to infants by appending a letter ("A" and "B" in this scenario) to the mother's ID. Here, the relationship between an associated person and a study subject is represented in APRELSUB.

aprelsub.xpt

RowSTUDYIDAPIDRSUBJIDSREL
1ABC-1101A101SON, BIOLOGICAL
2ABC-1101B101DAUGHTER, BIOLOGICAL

When the infant and the mother are both study subjects, they are each assigned a unique subject identifier (USUBJID) and the relationship is defined in the RELSUB dataset. The RELSUB dataset always shows each relationship between 2 study subjects using 2 records, since relationships (represented in SREL) are generally not symmetrical.

Example

This example is for a study in which both mothers and infants were study subjects. In this example, a mother gave birth to twins and the sponsor assigned unique subject identifiers (USUBJID) to infants by appending a letter ("A" and "B" in this scenario) to the mother's unique subject identifier (USUBJID).

Rows 1-2:Show the relationships between the mother and the first infant.
Rows 3-4:Show the relationships between the mother and the second infant.

relsub.xpt

RowSTUDYIDUSUBJIDRSUBJIDSREL
1ABC-2101101AMOTHER, BIOLOGICAL
2ABC-2101A101SON, BIOLOGICAL
3ABC-2101101BMOTHER, BIOLOGICAL
4ABC-2101B101DAUGHTER, BIOLOGICAL

When the infant is the study subject and the mother is an associated person, the relationship can be represented in the APRELSUB dataset. Relationships are described as the relationship of the associated person to the study subject, so only 1 record is required for each relationship.

Example

Infants were study subjects in this study; their mothers were associated persons. In this example, twins with the study identifiers "101" and "102" were study subjects. Their mother was an associated person. Because she was related to 2 different study subjects, the APRELSUB dataset was required to represent her relationships to study subjects. In this study, the sponsor assigned identifiers to mothers by appending "M" to infant study identifiers. In this case, the sponsor chose the identifier "101M" for the mother based on the identifier of 1 of the twins.

aprelsub.xpt

RowSTUDYIDAPIDRSUBJIDSREL
1ABC-3101M101MOTHER, BIOLOGICAL
2ABC-3101M102MOTHER, BIOLOGICAL

5.3 Representation of Pregnancy-related Events

Pregnancies are represented as events. A woman could become pregnant more than once during a long study. In this TAUG-HIV, --LNKID is used as a pregnancy identifier, to link data within and across domains for the same pregnancy.

The amount of data collected about pregnancy outcome is likely to depend on the time at which the pregnancy ends. In this guide, 20 weeks has been used as the dividing line between early and late pregnancy outcomes. The 20-week division is derived from the definitions of spontaneous abortion (also known as miscarriage) as something that happens before 20 weeks, and late fetal death as something that happens after 20 weeks. ( Complications of pregnancy are covered in Section 5.8, Routine Data for Mother-Infant Pairs.)

In this TAUG, pregnancy-related data are modeled as data about the mother, which means that pregnancies with multiple infants complicate the modeling when the outcome and the way in which the fetuses separate from the mother can differ. It is assumed that in an early pregnancy termination (before 20 weeks), the pregnancy end is the same for all fetuses, so separate records for multiple fetuses are not needed. A non-standard qualifier, Fetus/Infant Identifier (–FTINID), has been used to distinguish between multiple maternal records for pregnancies that end after 20 weeks. Although the SDTM includes the variable FETUSID, the variable is not intended for use in human clinical trials, and was intended only to distinguish between records for a particular test, not to be consistent across tests. The --FTINID in this guide is intended to identify fetuses consistently across records at a particular time (e.g., at birth), but not necessarily across times (e.g., across ultrasounds at various times during pregnancy).

The outcome of a pregnancy is modeled as an attribute of the mother's pregnancy as "Early pregnancy termination", "Late fetal death", "Stillbirth", or "Live birth", although there is an outcome for each fetus. This combines survival of the fetus with the stage at which a non-surviving fetus died.

The way in which a fetus is separated from the mother may be natural, as in a miscarriage or an unassisted vaginal delivery, or by means of an intervention such as an induced abortion or a Cesarean delivery. In the examples below, all ways in which a pregnancy ends are modeled as events, with the rationale that all (with the possible exception of live birth) are things which might be reported as adverse events. Events which can also be considered interventions present a choice for the sponsor, similar to the choice of whether to create a Procedures (PR) domain record for procedures whose main purpose is to gather data reported in findings domains. In the examples below, surgical abortion, surgical termination of an ectopic pregnancy, Cesarean delivery, forceps-assisted vaginal delivery, and vacuum-assisted vaginal delivery are modeled as procedures; medication-induced abortion and termination of an ectopic pregnancy are modeled as a concomitant medication administrations. Some of the data collected in the examples below, such as the urgency of a cesarean delivery or the medication used to induce pregnancy termination, are interventions data, and are best represented in an interventions record or a supplemental qualifier to an interventions record. If such data are not collected, the sponsor can decide whether to create interventions records for interventions that separate a fetus from its mother.

This modeling is illustrated in the following concept map, which includes SDTM domains and selected variables.

Concept Map. Pregnancy-Related Data

The following examples show pregnancy-related data as it would appear in the categories of studies described in Section 5.2, Identifiers and Relationships for Mother-Infant Pairs.

Example

This is an example in which women are study subjects, and any data about their infants are represented in Associated Persons (AP) datasets.


This example CRF shows data collected about a pregnancy. Different data are collected for pregnancies that lasted less than and more than 20 weeks. In this example, the 2 identifier variables --LNKID and CEFTINID are shown as though they were entered, but in an electronic data-capture system, system variables that distinguish between instances of a form could be used as the basis for these identifier variables.

Pregnancy Outcome aCRF

Instructions

Complete for each pregnancy.

CECAT, CMCAT, PRCAT Pre-populated
PREGNANCY-RELATED EVENTS
CETERM Hidden/pre-populated
PREGNANCY
CELNKID, CEGRPID CELNKID, CMLNKID, PRLNKID, CEGRPID
_____
CESTDAT CESTDTC
_ _ / _ _ _ / _ _ _ _
CEENDAT CEENDTC, CMSTDTC, PRSTDTC
_ _ / _ _ _ / _ _ _ _
CRF Metadata
Observation ClassOrder NumberDomainTAUG ReferenceCDASH VariableQuestion TextPromptTypeCRF Completion InstructionsInformation for SponsorsMaps to the SDTMIG VariableMapping InstructionsControlled Terminology CodeList NamePermissible ValuesPre-specified ValueQuery DisplayList StyleHidden

1CEHIV v1.0CECAT, CMCAT, PRCATWhat is the category of the clinical event?Pregnancy-related Eventstext

CECAT, CMCAT, PRCAT


PREGNANCY-RELATED EVENTS



2CEHIV v1.0CETERMWhat is the clinical event term?Clinical Eventtext

CETERMMaps directly to the SDTMIG variable "CETERM".

PREGNANCY

Y

3CEHIV v1.0CELNKID, CEGRPIDWhich on-study pregnancy is this?Pregnancy Identifierinteger
In an electronic data capture system, this may be based on a system variable.CELNKID, CMLNKID, PRLNKID, CEGRPIDThe value collected is prepended with "PREG" then mapped to the SDTMIG variable CELNKID. This value in the SDTMIG variable CELNKID may also map to CMLNKID or PRLNKID depending on responses to "How did the pregnancy end?" in the form for pregnancies that last less then 20 weeks and to "What was the type of delivery?" in the form for pregnancies that last more than 20 weeks.






4CEHIV v1.0CESTDATWhen did the pregnancy start?Start Datedate

CESTDTCThis does not map directly to an SDTMIG variable. For the SDTM submission dataset, populate the SDTMIG variable CESTDTC in ISO 8601 format.






5CEHIV v1.0CEENDATWhen did the pregnancy end?End Datedate

CEENDTC, CMSTDTC, PRSTDTCThis does not map directly to an SDTMIG variable. For the SDTM submission dataset, populate the SDTMIG variable CEENDTC in ISO 8601 format. This may also map to CMSTDTC or PRSTDTC depending on responses to "How did the pregnancy end?" in the form for pregnancies that last less then 20 weeks and to "What was the type of delivery" in the form for pregnancies that last more than 20 weeks.





Instructions

If the pregnancy lasted less than 20 weeks, fill in this form.

CESCAT Hidden/pre-populated
PREGNANCY OUTCOME
OUTCOME_CETERM CETERM Hidden/pre-populated
EARLY PREGNANCY TERMINATION
Select the most appropriate response.What is the clinical event term?
END_CETERM CETERM, CMINDC, PRTRT
END_CMTRT CMTRT
_________________
CRF Metadata
IDOrderQuestion TextPromptCRF Completion InstructionsTypeCDASH VariableMaps to the SDTMIG VariableMapping InstructionsControlled Terminology CodeList NamePermissible ValuesPre-specified ValueQuery DisplayList StyleHidden

1What is the subcategory of the clinical event?Pregnancy Outcome
textCESCATCESCATMaps directly to the SDTMIG variable CESCAT.

PREGNANCY OUTCOME

Y

2What is the clinical event term?Early Pregnancy Termination
textOUTCOME_CETERMCETERMMaps directly to the SDTMIG variable CETERM.

EARLY PREGNANCY TERMINATION

Y

3What is the clinical event term?Pregnancy EndSelect the most appropriate response.textEND_CETERMCETERM, CMINDC, PRTRTMaps directly to the SDTMIG variable CETERM. If the response is one of the surgical responses, it also maps to PRTRT. If the response is one of the medication-induced responses, then the term (less the text "Medication-induced") also maps to CMINDC.
Miscarriage;Surgical abortion;Surgical ectopic pregnancy termination;Medication-induced abortion;Medication-induced ectopic pregnancy termination

radio

4If medication-induced ectopic pregnancy termination, what was the medication name?Medication
textEND_CMTRTCMTRTMaps directly to the SDTMIG variable CMTRT.





Instructions

If the pregnancy lasted 20 weeks or more, provide the number of fetuses in the pregnancy.

CEFETNUM
_____
CRF Metadata
Observation ClassOrder NumberDomainTAUG ReferenceCDASH Variable NameQuestion TextPromptTypeCRF Completion InstructionsInformation for SponsorsMaps to the SDTMIG VariableMapping InstructionsControlled Terminology Codelist NamePermissible ValuesPrespecified ValueQuery DisplayList StyleHidden

5CEHIV v1.0CEFETNUMWhat is the number of fetuses in the pregnancy?Number of Fetuses in Pregnancyinteger
May be unknownCEFETNUMThis does not map directly to an SDTMIG variable. This information could be submitted in an NSV dataset as the value of the non-standard variable CEFETNUM. Refer to the current SDTM and SDTMIG for instructions on placement of non-standard variables in SDTM domains.





Instructions

If the pregnancy lasted 20 weeks or more, fill in this form for each gestation.

CEFTINID CEFTINID, PRFTINID
_____
CESCAT Hidden/pre-populated
PREGNANCY OUTCOME
Select the most appropriate response.What is the clinical event term?
OUTCOME_CETERM CETERM
Select the most appropriate response.If still birth or live birth, what was the setting?
OUTCOME_CESETTNG CESETTNG

<From SETTING codelist>

OUTCOME_CESETTOTH CESETTING
_________________
Select the most appropriate response.What was the type of delivery?
DELIVERY_CETERM CETERM, PRTRT
Select the most appropriate response.If forceps- or vacuum-assisted vaginal delivery, what was the location in the birth canal?
BCLOC_PRTRT PRBCLOC
Select the most appropriate response.If cesarean delivery, what was the urgency?
PRURGNCY

<From PRURGNCY codelist>

CRF Metadata
IDOrderQuestion TextPromptCRF Completion InstructionsTypeCDASH VariableMaps to the SDTMIG VariableMapping InstructionsControlled Terminology CodeList NamePermissible ValuesInformation for SponsorsPre-specified ValueQuery DisplayList StyleHidden

1
Fetus or Infant Identifier
integerCEFTINIDCEFTINID, PRFTINIDThis does not map directly to an SDTMIG variable. This information could be submitted in an NSV dataset as the value of the NSV CEFTINID and of the NSV PRFTIND . Refer to the current SDTM and SDTMIG for instructions on placement of NSV in SDTM domains.

In an electronic system, this would be automated based on a system variable.




2What is the subcategory of the clinical event?Pregnancy Outcome
textCESCATCESCATMaps directly to the SDTMIG variable CESCAT.


PREGNANCY OUTCOME

Y

3What is the clinical event term?Pregnancy OutcomeSelect the most appropriate response.textOUTCOME_CETERMCETERMThis maps directly to the SDTMIG variable CETERM.
Late fetal death; Still birth; Live birth


radio

5If still birth or live birth, what was the setting?Setting of BirthSelect the most appropriate response.textOUTCOME_CESETTNGCESETTNGThis does not map directly to an SDTMIG variable. This information could be submitted in an NSV dataset as the value of the NSV CESETTNG . Refer to the current SDTM and SDTMIG for instructions on placement of NSV in SDTM domains.(SETTING)Home; Hospital; Clinic; Other


radio

6If Other, specify.Other Setting of Birth
textOUTCOME_CESETTOTHCESETTINGThis does not map directly to an SDTMIG variable. This information could be submitted in an NSV dataset as the value of the NSV CESETTNG . Refer to the current SDTM and SDTMIG for instructions on placement of NSV in SDTM domains.







7What was the type of delivery?Type of DeliverySelect the most appropriate response.textDELIVERY_CETERMCETERM, PRTRT
This term maps directly to the SDTMIG variable CETERM. It also maps directly to the SDTMIG variable PRTRT if the value chosen is not "Unassisted vaginal delivery".

Unassisted vaginal delivery; Forceps-assisted delivery; Vacuum-assisted delivery; Cesarean delivery


radio

8If forceps- or vacuum-assisted vaginal delivery, what was the location in the birth canal?Birth Canal LocationSelect the most appropriate response.textBCLOC_PRTRTPRBCLOC
This does not map directly to an SDTMIG variable. This information could be submitted in an NSV dataset as the value of the NSV PRBLOC, where PRTRT=" Forceps-assisted delivery" or PRTRT="Vacuum-assisted delivery". Refer to the current SDTM and SDTMIG for instructions on placement of NSV in SDTM domains.

Low-cavity; Mid-cavity


radio

9If cesarean delivery, what was the urgency?UrgencySelect the most appropriate response.textPRURGNCYPRURGNCYThis does not map directly to an SDTMIG variable. This information could be submitted in an NSV dataset as the value of the NSV PRURGNCY, where PRTRT="c esarean delivery". Refer to the current SDTM and SDTMIG for instructions on placement of NSV in SDTM domains.(PRURGNCY)Elective; Emergency




The data collected on this CRF would be represented in up to 3 datasets:

  • Clinical Events (CE) for pregnancy, pregnancy outcome, and natural ends to pregnancy;
  • PR for procedures which ended pregnancy; and
  • Concomitant/Prior Medications (CM) for medication-induced pregnancy terminations.

In this example, the non-standard identifier CEFTINID was used to distinguish between infants in a multiple-gestation pregnancy. The CESPID variable was considered for this purpose but was not used, because --SPID is a sponsor-defined variable for which a sponsor may have other uses.


The CE dataset has at least 2 records for each pregnancy: a record for the pregnancy and a record for pregnancy outcome. Pregnancies of more than 20 weeks with more than 1 fetus have a pregnancy outcome record for each fetus. Natural ends of pregnancy (e.g., miscarriage, unassisted vaginal birth) are also represented in the CE domain.

Rows 1-6:Show 2 pregnancies for the same subject, distinguished by CELNKID="PREG1" or "PREG2". Both pregnancies had outcomes of "Early pregnancy termination", both by miscarriage.
Rows 7-8:Show a pregnancy that ended in late fetal death.
Rows 9-13:Show events related to a pregnancy with 2 fetuses. The fetus identified by --FTINID="1" experienced unassisted vaginal delivery, and was stillborn in a vehicle. The fetus identified by --FTINID="2" was born alive in a hospital and delivered by Cesarean delivery. The sponsor also represented the cesarean delivery in a PR domain record linked to records in CE using CELNKID and PRLNKID.
Rows 14-16:Show a pregnancy that terminated early. The pregnancy ended in a procedure which was also represented in the PR domain, linked to the CE records using CELNKID and PRLNKID.
Rows 17-19:Show a singleton pregnancy that resulted in a live birth in a hospital by forceps-assisted vaginal delivery. The forceps-assisted vaginal delivery was also represented in the PR domain, linked to the CE records using CELNKID and PRLNKID.
Rows 20-22:Show another pregnancy that ended early. In this case, the pregnancy was ended by administration of a medication, represented in the CM domain and linked to CE records using CMLNKID.

ce.xpt

RowSTUDYIDDOMAINUSUBJIDCESEQCELNKIDCETERMCECATCESCATCESTDTCCEENDTC
CEFETNUMCEFTINIDCESETTNG
1ABC-123CE1011PREG1PregnancyPREGNANCY-RELATED EVENTS
2017-01-102017-05-15



2ABC-123CE1012PREG1Early pregnancy terminationPREGNANCY-RELATED EVENTSPREGNANCY OUTCOME2017-05-15




3ABC-123CE1013PREG1MiscarriagePREGNANCY-RELATED EVENTS
2017-05-15




4ABC-123CE1014PREG2PregnancyPREGNANCY-RELATED EVENTS
2017-07-042017-09-02



5ABC-123CE1015PREG2Early pregnancy terminationPREGNANCY-RELATED EVENTSPREGNANCY OUTCOME2017-05-15




6ABC-123CE1016PREG2MiscarriagePREGNANCY-RELATED EVENTS
2017-09-02




7ABC-123CE1021PREG1PregnancyPREGNANCY-RELATED EVENTS
2017-11-232018-06-18
1

8ABC-123CE1022PREG1Late fetal deathPREGNANCY-RELATED EVENTSPREGNANCY OUTCOME2017-06-18




9ABC-123CE1031PREG1PregnancyPREGNANCY-RELATED EVENTS
2017-01-102017-10-25
2

10ABC-123CE1032PREG1StillbirthPREGNANCY-RELATED EVENTSPREGNANCY OUTCOME2017-10-25


1VEHICLE
11ABC-123CE1033PREG1Unassisted vaginal deliveryPREGNANCY-RELATED EVENTS
2017-10-25


1
12ABC-123CE1034PREG1Live birthPREGNANCY-RELATED EVENTSPREGNANCY OUTCOME2017-10-25


2HOSPITAL
13ABC-123CE1035PREG1Cesarean deliveryPREGNANCY-RELATED EVENTS
2017-10-25


2
14ABC-123CE1041PREG1PregnancyPREGNANCY-RELATED EVENTS
2017-02-272017-05-15
1

15ABC-123CE1042PREG1Early pregnancy terminationPREGNANCY-RELATED EVENTSPREGNANCY OUTCOME2017-05-15

1

16ABC-123CE1043PREG1Surgical ectopic pregnancy terminationPREGNANCY-RELATED EVENTS
2017-05-15

1

17ABC-123CE1051PREG1PregnancyPREGNANCY-RELATED EVENTS
2017-09-232018-06-01
1

18ABC-123CE1052PREG1Live birthPREGNANCY-RELATED EVENTSPREGNANCY OUTCOME2017-06-01


1HOSPITAL
19ABC-123CE1053PREG1Forceps-assisted deliveryPREGNANCY-RELATED EVENTS
2018-06-01


1
20ABC=23CE1061PREG1PregnancyPREGNANCY-RELATED EVENTS
2017-06-222017-08-14



21ABC=23CE1062PREG1Early pregnancy terminationPREGNANCY-RELATED EVENTSPREGNANCY OUTCOME2017-08-14




22ABC=23CE1063PREG1Medication-induced ectopic pregnancy terminationPREGNANCY-RELATED EVENTSPREGNANCY OUTCOME2017-08-14




CE NSV Metadata

The termination of a subject's ectopic pregnancy by means of the administration of a medication was represented in the CM domain, with "Ectopic pregnancy termination" as the indication.

cm.xpt

RowSTUDYIDDOMAINUSUBJIDCMSEQCMLNKIDCMTRTCMINDCCMDOSFRQCMSTDTCCMSTDY
1ABC-103CM1061PREG1MethotrexateEctopic pregnancy terminationONCE2017-08-1462

The sponsor represented termination of pregnancies by surgical means with records in the PR domain.

Row 1:Shows that for the infant identified with --FTINID="2", pregnancy ended in cesarean delivery. The urgency of this procedure was represented with the non-standard variable PRURGNCY.
Row 2:Shows an ectopic pregnancy that was terminated surgically. PRFTINID is null since identifiers were not assigned to fetuses in pregnancies that ended before 20 weeks.
Row 3:Shows the forceps-assisted delivery for the fetus identified with --FTINID="1". The classification of the forceps delivery as "LOW" was represented in the NSV PRBCLOC.

pr.xpt

RowSTUDYIDDOMAINUSUBJIDPRSEQPRLNKIDPRTRTPRCATPRSTDTC
PRFTINIDPRURGNCYPRBCLOC
1ABC-123PR1031PREG1Cesarean deliveryPREGNANCY-RELATED PROCEDURES2017-10-25
2EMERGENCY
2ABC-123PR1041PREG1Surgical ectopic pregnancy terminationPREGNANCY-RELATED PROCEDURES2017-05-15



3ABC-123PR1051PREG1Forceps-assisted deliveryPREGNANCY-RELATED PROCEDURES2017-06-01
1
LOW

PR NSV Metadata

Pregnancies, pregnancy outcomes, and ends of pregnancies were represented in CE. Ends of pregnancies that were also procedures or medication administrations were also represented in the PR or CM domains. The RELREC links pregnancy-related records using --LNKID records at the maternal level. Linking procedures to a particular fetus also requires the use of --FTINID, but RELREC only allows 1 linking variable.

relrec.xpt

RowSTUDYIDRDOMAINUSUBJIDIDVARIDVARVALRELTYPERELID
1ABC-123CE
CELNKID
MANY1
1ABC-123PR
PRLNKID
MANY1
1ABC-123CM
CMLNKID
ONE1

In a study in which mothers and infants were study subjects, pregnancy-related data would be represented as in the case when only the mother is a study subject. Note that since the information is represented in records for the mother, this information is associated with infants only indirectly. When a pregnancy includes only 1 fetus, the association between maternal and infant data would be adequately represented by the mother-infant relationships in RELSUB. For multiple pregnancies, the relationship between a fetal identifier in a maternal record and a USUBJID in an infant record (CEFTINID in the example above) cannot currently be represented in the SDTM. This relationship would be explained in a comment to USUBJID and/or SUBJID in the Define-XML document and/or in the Clinical Study Data Reviewers Guide (cSDRG).

In the studies on which the TAUG-HIV was based, only live-born infants were considered study subjects and prenatal data were treated as data about the mother. Other studies might take a different approach and treat fetuses as study subjects.

Example

This is an example of a study in which infants were study subjects, and any data about their mothers was represented in AP domains. In this example, pregnancy-related events were collected as in Example 1. However, because data on screen failures were not submitted, only data for mothers with live-born infants were submitted, and the resulting data were represented in APCE. The sponsor chose to base the mother's APID value on her infant's USUBJID, but with an appended "M". In the case of multiple infants, one infant's USUBJID was chosen for use in constructing the mother's APID. Note:

  • This example shows data for twins, both of whom were born alive; in the multiple pregnancy in Example 1, only 1 twin survived. The current example also includes an example of a single birth.
  • Although this example used a non-standard qualifier ("CEFTINID"), a sponsor could use a standard variable, such as CESPID, for this purpose. This example did not use CESPID in order to avoid creating the impression that a --SPID variable (which is sponsor-defined), should be used for the particular purpose illustrated in this example.
  • Because maternal data was collected for only the pregnancy involving the infant study subject, there was no need to use RELREC to link records for a particular pregnancy.
Row 1:Shows a mother's pregnancy with 2 gestations, associated with 2 study subjects (101 and 102); RSUBJID is populated with "MULTIPLE". When an associated person has relationships to multiple subjects, a single value of "SREL" is usually inadequate; the SDTMIG-AP directs that SREL should be "MULTIPLE". In this case, the mother's relationship to both infants was the same, but the sponsor followed the rule in the SDTMIG-AP and populated RSUBJID with "MULTIPLE". The identifiers of the multiple subjects and the mother's relationship to each of them are in the APRELSUB dataset.
Rows 2-3:Show data about the live birth and delivery of 1 twin. Because these records are associated with only one study subject, the sponsor populated SREL with the "MOTHER, BIOLOGICAL" and USUBJID with "101".
Rows 4-5:Show data about the live birth of the other twin. This infant's cesarean delivery was also represented in the APPR domain.
Rows 6-8:Show data about a singleton pregnancy. All data are associated with the subject with USUBJID = "103". This infant's forceps-assisted delivery was also represented in the APPR domain.

apce.xpt

RowSTUDYIDDOMAINAPIDCESEQRSUBJIDSRELCETERMCECATCESCATCESTDTCCEENDTC
CEFETNUMCEFTINIDCESETTNG
1XYZ-456CE101M1MULTIPLEMULTIPLEPregnancyPREGNANCY-RELATED EVENTS
2017-01-262017-10-25
2

2XYZ-456CE101M2101MOTHER, BIOLOGICALLive birthPREGNANCY-RELATED EVENTSPREGNANCY OUTCOME2017-10-25


1VEHICLE
3XYZ-456CE101M3101MOTHER, BIOLOGICALUnassisted vaginal deliveryPREGNANCY-RELATED EVENTS
2017-10-25


1
4XYZ-456CE101M4102MOTHER, BIOLOGICALLive birthPREGNANCY-RELATED EVENTSPREGNANCY OUTCOME2017-10-25


2HOSPITAL
5XYZ-456CE101M5102MOTHER, BIOLOGICALCesarean deliveryPREGNANCY-RELATED EVENTS
2017-10-25


2
6XYZ-456CE103M1103MOTHER, BIOLOGICALPregnancyPREGNANCY-RELATED EVENTS
2016-09-152017-06-01
1

7XYZ-456CE103M2103MOTHER, BIOLOGICALLive birthPREGNANCY-RELATED EVENTSPREGNANCY OUTCOME2017-06-01


1HOSPITAL
8XYZ-456CE103M3103MOTHER, BIOLOGICALForceps-assisted deliveryPREGNANCY-RELATED EVENTS
2017-06-01


1

APCE NSV Metadata

Cesarean and assisted deliveries were represented in the PR domain.

Row 1:Shows that for the infant identified with --FTINID = "2", the pregnancy ended in Cesarean delivery. The urgency of this procedure was represented with the non-standard variable PRURGNCY.
Row 2:Shows the forceps-assisted delivery for the fetus identified with --FTINID = "1". The classification of the forceps delivery as "LOW" was represented in the NSV PRBCLOC.

appr.xpt

RowSTUDYIDDOMAINAPIDPRSEQRSUBJIDSRELPRTRTPRCATPRSCATPRPRESPPROCCURPRINDCPRSTDTCPRENDTCPRSTDYPRENDY
PRFTINIDPRURGNCYPRBCLOC
1ABC-123PR101M1102MOTHER, BIOLOGICALCesarean deliveryPREGNANCY-RELATED PROCEDURES



2017-10-25



2EMERGENCY
2ABC-123PR103M1103MOTHER, BIOLOGICALForceps-assisted deliveryPREGNANCY-RELATED PROCEDURES



2017-06-01



1
LOW

APPR NSV Metadata

5.4 Gestational Age

Estimations of gestational age may be based on examinations performed on a pregnant woman or on a newborn infant. Note that gestational age can be estimated at any time during pregnancy, although after birth "gestational age" is commonly used to refer to the gestational age at birth. Example 1 shows the representation of estimated gestational age, and Example 2 the representation of various kinds of data from which gestational age may be estimated.

Example

In this example, only infants were study subjects. However, with the possible exception of USUBJID values, the example would be unchanged for a study in which mothers were study subjects. If these data were collected for an infant who was an associated person, they would be represented in the APSC domain and the dataset would include APID, RSUBJID, and SREL, rather than USUBID.


Although there is a test for gestational age in the CDISC Controlled Terminology for Reproductive Findings, gestational age is an attribute of the fetus or infant, and is not a finding about their reproductive system; in this example, gestational age is represented in the Subject Characteristics (SC) domain. The structure of the SC domain is currently 1 record per characteristic (test) per subject, but it is expected that the structure will allow multiple records per test in the future. This example shows multiple estimates of gestational age for the same subject. In this example, estimated gestational age is shown as a finding about the mother, rather than the infant. In cases of a multiple-gestation pregnancies, separate estimates for different fetuses are distinguished using an identifier such as the non-standard identifier SCFTIND used in this example. Not all of the values of METHOD shown in this example are currently in the METHOD codelist.


Gestational age is often expressed (and sometimes collected) in weeks and days. SDTM does not support the recording of an individual finding result with mixed units (e.g., "20 weeks and 5 days"), so the gestational age would be converted to days for representation in SDTM.

Rows 1-2:Prenatal estimates of gestational age were obtained by 2 different methods at Visits 10 and 11.
Row 3:Gestational age was estimated shortly after birth by physical examination of the infant. Birth did not occur during a regularly scheduled visit. Because it occurred between scheduled Visits 13 and 14, the sponsor assigned a visit number of 13.1 to data collected at that time.

sc.xpt

RowSTUDYIDDOMAINUSUBJIDSCSEQSCTESTCDSCTESTSCCATSCORRESSCORRESUSCSTRESCSCSTRESNSCSTRESUSCMETHODVISITNUMSCDTCSCDY
SCFTINID
1ABC-123SC1011EGESTAGEEstimated Gestational AgePREGNANCY-RELATED FINDINGS100DAYS100100DAYSMENSTRUAL HISTORY102017-03-02196
1
2ABC-123SC1012EGESTAGEEstimated Gestational AgePREGNANCY-RELATED FINDINGS135DAYS135135DAYSULTRASOUND1120-17-04-01226
1
3ABC-123SC1013EGESTAGEEstimated Gestational AgePREGNANCY-RELATED FINDINGS265DAYS265265DAYSBALLARD13.120-17-06-10297
1

SC NSV Metadata

If data to support an estimate of gestational age are collected, the domain in which those data are represented depends on the nature of the supporting data. If study data for estimated gestational age did have supporting data, the relationship between the estimated gestational age record in SC and the supporting data in another domain would be represented in RELREC.

The Ballard score is an assessment of physical characteristics of a newborn from which gestational age may be estimated. This is a clinical classification that would be represented in the Disease Response and Clinical Classification (RS) domain. Development of a supplement for this scale has been requested. See Section 7.6, Questionnaires, Ratings, and Scales, for further information about QRS supplements.

Gestational age may be estimated from the date of the last menstrual period, which is the start date of the event "Menstrual period". In a study that enrolled pregnant women, the most recent menstrual period would be represented in MH, using a form similar to that shown in Section 4.1, Baseline Menstrual History. In a study where the last menstrual period occurred during the study, it would be represented in the Clinical Events (CE) domain.

Example

In this example, a pregnant woman was a study subject. Whether infants were study subjects would not affect this example.


In this example, the date of the start of the last menstrual period was collected if a woman became pregnant during the study. The non-standard variable CECRNORD="MOST RECENT" represents the relationship of the particular menstrual period relative to the date of collection (CEDTC). The collected start date is represented in CESTDTC.

ce.xpt

RowSTUDYIDDOMAINUSUBJIDCESEQCEGRPIDCETERMCECATCEDTCCESTDTC
CECRNORD
1ABC-123CE1011PREG1Menstrual periodPREGNANCY-RELATED EVENTS2017-05-152017-03-01
MOST RECENT
2ABC-123CE1012PREG2Menstrual periodPREGNANCY-RELATED EVENTS2017-09-022017-07-23
MOST RECENT

CE NSV Metadata

Fundal height, which is the distance from the top of the pubic bone to the top of the uterus assessed by palpation, can be used to estimate gestational age. Because this test is a measurement of the uterus, it is represented in the Reproductive System Findings (RP) domain.

Example

In this example, a pregnant woman was a study subject. Whether infants were study subjects would not affect this example.


The values for RPTEST and RPTESTCD shown in this example are not in current published controlled terminology. The value of RPCAT reflects the name of the CRF module in which this measurement was collected.

rp.xpt

RowSTUDYIDDOMAINUSUBJIDRPSEQRPGRPIDRPTESTCDRPTESTRPCATRPORRESRPORRESURPSTRESCRPSTRESNRPSTRESUVISITNUMRPDTC
1ABC-123RP1031PREG1FUNDHTFundal HeightPREGNANCY-RELATED EVENTS28cm2828cm42016-07-13

Gestational age can also be estimated from ultrasound measurements of a fetus in utero. Body measurements such as head circumference and bone lengths are represented in the Vital Signs (VS) domain.

Example

In this example, a pregnant woman was a study subject. Whether infants were study subjects would not affect this example. This example shows only 1 of the measurements that may be used to estimate gestational age. Fetal ultrasound measurements were treated as findings about the mother, who undergoes the procedure; results are generally entered in the mother's charts. In the case of multiple births, fetal measurements are distinguished from each other, but measurements made on different occasions may not be associated with the same fetus. That is, measurements at different times might be recorded as for Fetus 1 and Fetus 2, but Fetus 1 at the 2 occasions may or may not be the same fetus. Given this situation, it did not seem appropriate to assign an APID (or a USUBJID, depending on the study situation) to fetal measurements. This might be approached differently in a study in which an effort is made to assign invariant identifiers to fetuses. In this example, the non-standard identifier VSFTINID was used to distinguish between infants in a multiple-gestation pregnancy. The VSSPID variable was considered for this purpose but was not used, because --SPID is a sponsor-defined variable for which a sponsor may have other uses.


The test terminology shown here, which includes "fetal" to describe the measurements, was not in CDISC Controlled Terminology at the time of publication of this user guide, but the terms are similar to existing SEND controlled terms such as "Fetal Body Weight". In cases of multiple-gestation pregnancies, separate estimates for different fetuses are distinguished using the non-standard identifier VSFTINID.

vs.xpt

RowSTUDYIDDOMAINUSUBJIDVSSEQVSGRPIDVSTESTCDVSTESTVSCATVSORRESVSORRESUVSSTRESCVSSTRESNVSSTRESUVISITNUMVSDTC
VSFTINID
1ABC-123VS1031PREG1FTHDCIRCFetal Head CircumferencePREGNANCY-RELATED EVENTS25cm2525cm32016-04-16
1
2ABC-123VS1032PREG1FTHDCIRCFetal Head CircumferencePREGNANCY-RELATED EVENTS28cm2828cm32016-04-16
2

VS NSV Metadata


5.5 Infant Demographics Data

In studies in which the infant is considered an associated person, demographics data will be limited. Many of the date variables in the Demographics (DM) domain are dates that refer to study participation, which do not apply to an associated person and would not be included in an APDM dataset.

Example

In this example, mothers were study subjects, and any data about infants were represented in associated persons (AP) domains.


In this example, only live-born infants were considered to be associated persons; data about fetuses who were not born live was considered maternal data. Birth date and sex were the only demographic data collected about infants. Other demographic data were not included because they are neither expected nor required in the APDM domain.


Controlled terminology values for the relationship of an associated person to a study subject include the gender-neutral term "CHILD, BIOLOGICAL" as well as the terms "DAUGHTER, BIOLOGICAL" and "SON, BIOLOGICAL". In this example, the gender-neutral term was used for all infants, but it would also be possible and valid to use the gender-specific terms.

apdm.xpt

RowSTUDYIDDOMAINAPIDRSUBJIDSRELBRTHDTCSEX
1ABC-123APDM103-2103CHILD, BIOLOGICAL2017-10-25M
2ABC-123APDM105-1105CHILD, BIOLOGICAL2017-06-01F

Demographics data include multiple dates related to study participation. In studies that recruit pregnant women and in which mothers and infants are study subjects, the meaning of these dates for an infant subject should be defined in the protocol:

  • The date of informed consent (i.e., informed assent for the infant), RFICDTC, will be before birth.
  • The dates of start and end of study treatment, RFXSTDTC and RFXENDTC, would depend on whether infants receive study treatment directly and whether indirect exposure in utero or via breast milk is included.
  • The study reference start date, RFSTDTC, should have the same definition for all study subjects, and have a meaning that will make --DY variables that reference this date useful. This choice may be difficult in studies that include both mothers and infants as study subjects.

Study participation dates in infant demographic data for studies in which only the infant is a study subject may be somewhat easier to define.

For instance, in the infant PK study example in Section 5.1, Studies Involving Mother-Infant Data, the study reference start date might be chosen as the date of birth or the date of start of direct study treatment.

5.6 Assessments of Infants at Birth

The examples in this section assume that the infant is a study subject. Data collected for an infant who was an associated person would be represented in the corresponding AP domain and the dataset would include APID, RSUBJID, and SREL, rather than USUBID.

Apgar scores and Ballard Maturational Assessments may be performed shortly after birth. Examples of data from these scales are not included here, as examples would be developed by the Questionnaires, Ratings, and Scales (QRS) Team. See Section 7.6, Questionnaires, Ratings, and Scales for additional information about these and other scales relevant to HIV studies.

Congenital anomalies would be recorded as adverse events for the infant.

Infant weight may be compared to a growth chart to determine whether an infant is small for gestational age (generally defined as having a weight less than the 10th percentile for gestational age).

Example

In this example, infants were study subjects. The USUBJID values in the example suggest that mothers were also study subjects, but with the possible exception of USUBJID values, the example would be unchanged for a study in which mothers were associated persons.


In this example, infants were weighed at birth, and their weight was compared to a growth chart to determine whether they were small for gestational age. The date of collection is the infant's date of birth, which can be obtained from the Demographics (DM) record for the infant. The infant in this example had a gestational age of 280 days (40 weeks), as determined by the Ballard method of examination, and was considered small for gestational age..

vs.xpt

RowSTUDYIDDOMAINUSUBJIDVSSEQVSTESTCDVSTESTVSORRESVSORRESUVSSTRESCVSSTRESNVSSTRESUVSDTC
1ABC-2VS105A1WEIGHTWeight2050g20502050g2015-02-03
Row 1:Shows gestational age for an infant using the Ballard examination, represented by SCMETHOD="BALLARD".
Row 2:Shows that an infant was determined to be small for gestational age. SCMETHOD="FENTON 2013" was used to indicate the growth chart to which the infant's weight and gestational age were compared.

sc.xpt

RowSTUDYIDDOMAINUSUBJIDSCSEQSCTESTCDSCTESTSCORRESSCORRESUSCSTRESCSCSTRESNSCSTRESUSCMETHODSCDTC
1ABC-2SC105A1EGESTAGEEstimated Gestational Age280DAYS280280DAYSBALLARD2015-02-03
2ABC-2SC105A2SMGAINDSmall for Gestational Age IndicatorY
Y

FENTON 20132015-02-03

Fontanelle closure may also be assessed at birth.

Example

In this example, both mothers and infants were study subjects. However, with the possible exception of USUBJID values, the example would be unchanged for a study in which mothers were not study subjects.


The infant had a postnatal examination to assess the closure of the anterior and posterior fontanelle. The MKTEST, MKTESTCD, and MKLOC values shown in this example are not yet included in published controlled terminology at the time of publication of this user guide.

mk.xpt

RowSTUDYIDDOMAINUSUBJIDMKSEQMKTESTCDMKTESTMKCATMKORRESMKSTRESCMKLOCMKDTC
1ABC-2MK101A1FONTCLOSFontanelle Closure IndicatorPOSTNATAL EXAMNNANTERIOR FONTANELLE2015-01-24T13:24
2ABC-2MK101A2FONTCLOSFontanelle Closure IndicatorPOSTNATAL EXAMNNPOSTERIOR FONTANELLE2015-01-24T13:24

5.7 Infant Feeding

In studies where the infant is a study subject, data may be collected about infant feeding. Data about breastfeeding may be used in combination with maternal medication data to assess infant exposure to medications in breast milk.

Example

This is an example of a study in which infants were study subjects. The USUBJID values suggest that mothers were also study subjects; with the possible exception of USUBJID values, the example would be unchanged for a study in which mothers were associated persons. If these data were collected for an infant who was an associated person, they would be represented in the APML domain and the dataset would include APID, RSUBJID, and SREL, rather than USUBID.

In this study, data about infant feeding included:

  • An indication of whether the infant was breastfed
    • If the infant was not breastfed, the reason for not breastfeeding was collected.
    • If the infant was breastfed, the start and end dates of feeding with breast milk were collected.
  • An indication of whether the infant received formula
    • If the infant received formula, the start and end dates of feeding with formula were collected.
  • An indication of whether the infant received complementary food (i.e., food other than breast milk or formula)
    • If the infant received complementary food, the start date of feeding with complementary food was collected.

Data are shown for 2 infants; 1 was breastfed and the other was not.

ml.xpt

RowSTUDYIDDOMAINUSUBJIDMLSEQMLTRTMLPRESPMLOCCURMLSTDTCMLENDTC
MLREASOC
1ABC-2ML101A1BREAST MILKYY2016-03-182017-02-13

2ABC-2ML101A2FORMULAYY2016-08-25


3ABC-2ML101A3COMPLEMENTARY FOODYY2017-01-25


4ABC-2ML102A1BREAST MILKYN


MATERNAL ILLNESS
5ABC-2ML102A2FORMULAYY2016-04-01


6ABC-2ML102A3COMPLEMENTARY FOODYY2017-02-04


ML NSV Metadata

5.8 Routine Data for Mother-Infant Pairs

The SDTMIG provides advice on the collection of data such as vital signs, adverse events, and medications, and the SDTMIG-AP provides information on how to represent these kinds of data for associated persons. The following are a few points to consider in a study that involves mother-infant pairs.

Vital Signs

There is no specific test for "birth weight". Birth weight would be represented in a Vital Signs (VS) or APVS domain in a record with VSDTC equal to the birth date.

Medical Conditions

For study subjects, medical conditions are represented in Medical History (MH), Adverse Events (AE), or Clinical Events (CE), depending on when they occurred (MH for events that started before the study) and on whether the event is reportable as an adverse event in the particular study (the distinction between AE and CE). For associated persons, the distinctions are less clear. APMH tends to be used for medical conditions before the study subject started the study. For mothers who are associated persons for an infant study subject, however, the domain in which to represent events that occurred after the pregnant woman was recruited might be represented in CE or AE, even though the infant may not be considered to start the study until after birth.

Example

In this example, the mother is an associated person. If the mother were a study subject, the data would be represented in the MH domain and the dataset would include USUBID, rather than APID, RSUBJID, and SREL. The sponsor chose to represent these maternal events as medical history, because they occurred before the subject was born.

Rows 1-2:Show records for conditions which were prespecified in a CRF module for pregnancy complications. MHCAT="PREGNANCY COMPLICATIONS" to indicate the source module.
Rows 3-4:Show conditions that were not prespecified.

apmh.xpt

RowSTUDYIDDOMAINAPIDMHSEQRSUBJIDSRELMHTERMMHDECODMHCATMHPRESPMHOCCURMHSTDTCMHENDTC
1ABC-3APMH107M1107MOTHER, BIOLOGICALPreeclampsiaPreeclampsiaPREGNANCY COMPLICATIONSYY2015-09-032015-11-25
2ABC-3APMH107M2107MOTHER, BIOLOGICALPremature laborPremature laborPREGNANCY COMPLICATIONSYN

3ABC-3APMH107M3107MOTHER, BIOLOGICALFeverFever


2015-10-052015-10-09
4ABC-3APMH107M4107MOTHER, BIOLOGICALCoughCough


2016-01-082016-10-08

Medications

Maternal medications during pregnancy and lactation are likely to be of interest when the infant is a study subject. Which medications were taken during pregnancy and lactation may be ascertained by comparing intervention record dates with the date of birth and with dates of breastfeeding. When the mother is an associated person rather than a study subject, limited concomitant medication data might be collected, and the data might be collected in separate modules for medications taken during pregnancy and those taken during lactation. If so, then the collection module of origin could be represented in a value of the CMCAT or CMSCAT variable.

Example

In this example, the mother was an associated person. If she were an study subject, the data would be represented in the CM domain and the dataset would include USUBID, rather than APID, RSUBJID, and SREL. Data about her medications during breastfeeding were collected in a separate CRF module, and the name of module was used to populate CMCAT. This example shows modeling of a combination therapy with each drug and dosage listed separately. Either CMENRF or CMENRTPT can be used to represent data coming from the CMONGO variable. In this case, CMENRF was populated with PRIOR because the concomitant medications were not ongoing.



The Medication During Breastfeeding CRF was used in this infant PK study to collect information on medications taken by a mother.

Because the mother is not the actual subject, the Associated Persons SDTMIG domain APCM would be used. Within APCM, variable names use the Concomitant/Prior Medications (CM) domain prefix. Consult the SDTMIG and CDASHIG for CM variable-level metadata.

Where variable metadata do not already exist in the CDASHIG, the CDASH Implementation Guide provides guidance on developing variables based upon the CDASH and SDTM models and the SDTMIG.

The following are required SDTMIG variables for the APCM domain:

  • APID (Associated Persons Identifier)
  • SREL (Subject, Device or Study Relationship), prepopulated in this example with the value of "MOTHER, BIOLOGICAL" from the RELSUB codelist

Breastfeeding Medication Log

CMCAT Hidden/pre-populated
MEDICATION DURING BREASTFEEDING
Indicate if any concomitant medications were taken. If Yes, include the appropriate details where indicated on the CRF.Any Concomitant Medication(s)
CMYN Not submitted

<From NY codelist>

Record only 1 medication per line. Provide the full trade or proprietary name of the medication; otherwise, the generic name may be recorded.
CMTRT
_________________
Record the concomitant medication subcategory.What is the subcategory for the concomitant medication?
CMSCAT
Record the dose of concomitant medication taken per administration (e.g., 200).
CMDOSE
_________________
Record the dose unit of the dose of concomitant medication taken (e.g., mg).
CMDOSU
_________________

<From UNIT codelist>

Record how often the concomitant medication was taken (e.g., BID, PRN).
CMDOSFRQ
_________________

<From FREQ codelist>

Provide the route of administration for the concomitant medication.
CMROUTE
_________________

<From ROUTE codelist>

Record the date the concomitant medication was first taken, using this format: DD-MON-YYYY. If the subject has been taking the concomitant medication for a considerable amount of time prior to the start of the study, it is acceptable to have an incomplete date. Any concomitant medication taken during the study is expected to have a complete start date. Any prior concomitant medication that is exclusionary should have both a start and end date.
CMSTDAT CMSTDTC
_________________
Record the concomitant medication as ongoing or not, to indicate whether the subject has stopped taking the concomitant medication at the time of data collection. If the concomitant medication is ongoing, the end date should be left blank.Was the concomitant medication ongoing?
CMONGO CMENRF/CMENRTPT

<From NY codelist>

Record the date the concomitant medication was stopped, using this format: DD-MON-YYYY. If the subject has not stopped taking the concomitant medication, leave this field blank.
CMENDAT CMENDTC
_________________
CRF Metadata
Order NumberTAUG ReferenceCDASH VariableCDASHIG Variable LabelQuestion TextPromptCRF Completion InstructionsData TypeMaps to the SDTMIG VariableSDTMIG Variable MappingControlled Terminology CodeList NameCRF Implementation NotesPermissible ValuesPre-specified ValueQuery DisplayList StyleHidden
1TAUG-HIV v1.0CMCATConcomitant Medication CategoryWhat is the category for the concomitant medication?Concomitant Medication CategoryRecord the concomitant medication category, if not preprinted on the CRF.textCMCAT



MEDICATION DURING BREASTFEEDING

true
2TAUG-HIV v1.0CMYNAny Concomitant Medication(s)Were any concomitant medication(s) taken while breastfeeding?Any Concomitant Medication(s)Indicate if any concomitant medications were taken. If Yes, include the appropriate details where indicated on the CRF.text

(NY)
Yes;No
promptRadio
3TAUG-HIV v1.0CMTRTConcomitant MedicationWhat was the concomitant medication name?Concomitant MedicationRecord only 1 medication per line. Provide the full trade or proprietary name of the medication; otherwise, the generic name may be recorded.textCMTRT







4TAUG-HIV v1.0CMSCATConcomitant Medication SubcategoryWhat is the subcategory for the concomitant medication?Concomitant Medication SubcategoryRecord the concomitant medication subcategory.textCMSCAT


ANTIRETROVIRAL;GENERAL



5TAUG-HIV v1.0CMDOSEDose per administrationWhat was the individual dose of the concomitant medication per administration?Dose per administrationRecord the dose of concomitant medication taken per administration (e.g., 200).textCMDOSE







6TAUG-HIV v1.0CMDOSU(Dose) UnitWhat is the unit?(Dose) UnitRecord the dose unit of the dose of concomitant medication taken (e.g., mg).textCMDOSU
(UNIT)





7TAUG-HIV v1.0CMDOSFRQFrequencyWhat was the frequency of the concomitant medication?FrequencyRecord how often the concomitant medication was taken (e.g., BID, PRN).textCMDOSFRQ
(FREQ)





8TAUG-HIV v1.0CMROUTERouteWhat was the route of administration of the concomitant medication?RouteProvide the route of administration for the concomitant medication.textCMROUTE
(ROUTE)





9TAUG-HIV v1.0CMSTDATStart DateWhat was the concomitant medication start date?Start DateRecord the date the concomitant medication was first taken, using this format: DD-MON-YYYY. If the subject has been taking the concomitant medication for a considerable amount of time prior to the start of the study, it is acceptable to have an incomplete date. Any concomitant medication taken during the study is expected to have a complete start date. Any prior concomitant medication that is exclusionary should have both a start and end date.textCMSTDTC







10TAUG-HIV v1.0CMONGOConcomitant Meds OngoingWas the concomitant medication ongoing?Concomitant Meds OngoingRecord the concomitant medication as ongoing or not, to indicate whether the subject has stopped taking the concomitant medication at the time of data collection. If the concomitant medication is ongoing, the end date should be left blank.textCMENRF; CMENRTPTCMENRF/CMENRTPT(NY)This does not map directly to an SDTM variable. May be used to populate a value into an SDTMIG relative timing variable such as CMENRF or CMENRTPT. When populating CMENRF, if the value of CMONGO is "Y", the value of "DURING", "AFTER" or "DURING/AFTER" may be used. When populating CMENRTPT, if the value of CMONGO is "Y", the value of "ONGOING" may be used. When CMONGO refers to the Study Reference Period (defined in DM.RFSTDTC to DM.RFENDTC) the SDTM variable CMENRF should be populated. When CMONGO is used in conjunction with other time points, the SDTM variables CMENRTPT and CMENTPT should be used.
Note: CMENRTPT must refer to a time point anchor described in CMENTPT.
Yes;No

Radio
11TAUG-HIV v1.0CMENDATEnd DateWhat was the concomitant medication end date?End DateRecord the date the concomitant medication was stopped, using this format: DD-MON-YYYY. If the subject has not stopped taking the concomitant medication, leave this field blank.textCMENDTC







apcm.xpt

RowSTUDYIDDOMAINAPIDCMSEQRSUBJIDSRELCMTRTCMCATCMSCATCMDOSECMDOSUCMDOSFRQCMROUTECMDTCCMSTDTCCMENDTCCMENRF
1ABCAPCM1071107AMOTHER, BIOLOGICALEfavirenzMEDICATION DURING BREASTFEEDINGANTIRETROVIRAL600mgQDORAL2015-11-262015-09-032015-11-25PRIOR
2ABCAPCM1072107AMOTHER, BIOLOGICALEmtricitabineMEDICATION DURING BREASTFEEDINGANTIRETROVIRAL200mgQDORAL2015-11-262015-09-032015-11-25PRIOR
3ABCAPCM1073107AMOTHER, BIOLOGICALTenofovir disoproxil fumarateMEDICATION DURING BREASTFEEDINGANTIRETROVIRAL300mgQDORAL2015-11-262015-09-032015-11-25PRIOR

If the infant is a study subject, exposure to maternal medications may be represented in interventions domains. For these medications, however, the dose taken by the infant would not be known, so some dose-related domain variables would not be populated..

Example

In this example, mothers and infants were study subjects. However, with the possible exception of USUBJID values, the example would be unchanged for a study in which mothers were not study subjects. If these data were collected for an infant who was an associated person, they would be represented in the APML domain and the dataset would include APID, RSUBJID, and SREL, rather than USUBID.


This example shows infant exposure to study drug before birth and during breastfeeding. Because infant exposure data is derived from maternal data, only the EX dataset is shown. Since EXDOSE, EXDOSU, and EXDOSFRM are expected, they are included though not populated.

ex.xpt

RowSTUDYIDDOMAINUSUBJIDEXSEQEXTRTEXDOSEEXDOSUEXDOSFRMEXROUTEEXSTDTCEXENDTC
1ABC-2EX101A1CURALL


TRANSPLACENTAL2016-03-252016-07-04
2ABC-2EX101A2CURALL


TRANSMAMMARY2016-07-042016-12-18

6 Interventions for the Prevention and Treatment of HIV

6.1 HIV Treatment with Oral Antiretroviral Therapy (ART)

The goal of ART in the treatment of HIV is to slow progression of the disease by curbing the proliferation of the virus. Successful control of HIV by ART can significantly prolong life (as compared to uncontrolled HIV infection), as well as reduce the chances of the infected person passing the virus to others. ART consists of a combination of antiretroviral drugs (ARVs). Therapy of a single ARV is not used; they are always given in combinations consisting of multiple ARVs. For instance, recommendations for the initial treatment of HIV infection call for a combination of 3 or more ARVs from 2 or more drug classes.[11]

Handling data on drug regimens involving combination therapies can be complex and calls for more specific data modeling strategies than those illustrated in the current SDTMIG. In order to develop a unified approach to handling these data across all therapeutic areas, a stand-alone supplemental focused topic guide on combination therapies will be developed to include examples from multiple disease areas. Users should refer to the HIV ART example(s) in that guide for further information when that topic guide is published.

6.2 Pre-exposure Prophylaxis (PrEP)

Pre-exposure prophylaxis (PrEP) is defined as receiving antiviral drug(s) prior to exposure to prevent infection. Subjects receive ARV therapy prior to exposure to HIV to reduce the risk of becoming infected. PrEP may be an option for subjects who have a high risk of becoming infected with HIV and it may be taken for varying lengths of time, depending on risk.

Section 6.2.1, Vaginal Ring, provides an example of a vaginal ring containing an antiviral drug as a form of PrEP. Oral PrEP examples are not provided in the TAUG-HIV as the representation of this treatment is well handled by both the CDASHIG and the SDTMIG.

6.2.1 Vaginal Ring

Vaginal rings are one form of PrEP and have been shown to be an effective tool for women to reduce the risk of HIV transmission from infected sexual partners. The silicone ring is inserted into the vagina and it continuously releases an antiviral drug over the period of a month.

Example

In a hypothetical prevention study, investigators assessed the safety and efficacy of a vaginal ring containing approximately 25 mg of Study Drug A to prevent HIV infection. The study was conducted over a 3-month period, and women were instructed to insert each ring for 28 days. If the ring was removed for any reason, they were asked to record the information about the removal, including the removal date, reason for the removal, whether or not the ring was washed, and whether or not they reinserted the ring. After the 28 days, they were asked to return to the study site so that the ring could be removed and replaced. At this time, subjects provided a blood sample in order to determine the pharmacokinetic concentration of Drug A. The amount of Drug A remaining in the ring was also assessed at this time.


The following example shows study data from one subject (ABC-001) as described above over a 3-month period. The Device Identifiers (DI) domain shows identifying information for the 3 different rings dispensed to Subject ABC-001, including device type, lot number, and batch number. Each ring has a unique identifier, which is represented in the variable SPDEVID. This variable is used in several dataset examples below to identify data associated with each ring.

di.xpt

RowSTUDYIDDOMAINSPDEVIDDISEQDIPARMCDDIPARMDIVAL
1ABCDIRING5831DEVTYPEDevice TypeIntravaginal Ring
2ABCDIRING5832LOTLot NumberABC123
3ABCDIRING5833BATCHBatch Number6789
4ABCDIRING5841DEVTYPEDevice TypeIntravaginal Ring
5ABCDIRING5842LOTLot NumberABC456
6ABCDIRING5843BATCHBatch Number6710
7ABCDIRING5851DEVTYPEDevice TypeIntravaginal Ring
8ABCDIRING5852LOTLot NumberABC789
9ABCDIRING5853BATCHBatch Number6705

The Device Properties (DO) domain was used to represent information about the amount of study drug in each of the three rings before insertion. The amount of starting drug in a ring may vary slightly by batch. As shown in the preceding DI example, each ring comes from a different batch.

do.xpt

RowSTUDYIDDOMAINSPDEVIDDOSEQDOTESTCDDOTESTDOORRESDOORRESUDOSTRESCDOSTRESNDOSTRESU
1ABCDORING5831DRUGAAMTDrug A Amount24.978mg24.97824.978mg
2ABCDORING5841DRUGAAMTDrug A Amount24.854mg24.85424.854mg
3ABCDORING5851DRUGAAMTDrug A Amount24.975mg24.97524.975mg

The Device Exposure (DX) domain was used to show each time the was ring was inserted and removed. Two non-standard variables (--INSROL and --RMVROL) indicate the role of person who inserted or removed the ring, respectively. If the ring fell out on its own, the non-standard variable "--RMVROL" was left null. These 2 non-standard variables were populated using the CDISC "Evaluator" codelist. The reason for ring removal was represented by the standard variable --RSDISC (Reason for Treatment Discontinuation). If a ring is removed and then reinserted, it may be important to collect whether or not the ring was rinsed before reinsertion, as this may alter the amount of drug that is in the ring. The non-standard variable --RNSIND was used to represent this concept.

dx.xpt

RowSTUDYIDDOMAINUSUBJIDSPDEVIDDXSEQDXTRTDXRSDISCDXSTDTCDXENDTC
DXINSROLDXRMVROLDXRNSIND
1ABCDXABC-001RING5831Intravaginal Ring ARING FELL OUT2016-02-012016-02-22
HEALTH CARE PROFESSIONAL
N
2ABCDXABC-001RING5832Intravaginal Ring ARING DEPLETED2016-02-262016-02-28
STUDY SUBJECTHEALTH CARE PROFESSIONALY
3ABCDXABC-001RING5843Intravaginal Ring ARING DEPLETED2016-02-282016-03-26
HEALTH CARE PROFESSIONALHEALTH CARE PROFESSIONALN
4ABCDXABC-001RING5854Intravaginal Ring ASTUDY SUBJECT DECLINED2016-03-262016-04-10
HEALTH CARE PROFESSIONALSTUDY SUBJECTN

DX NSV Metadata

After the final removal of each ring, the concentration of drug found in the subject's plasma as well as the amount remaining in the ring was assessed. Ideally, the subject and the ring are assessed 28 days after the ring is initially inserted; thus the --TPT and --ELTM variables for each measurement were populated with the planned time of "28 DAYS AFTER RING INSERTION" and P28D, respectively. The variables --TPTREF and --RFTDTC, which are used to represent the ring insertion date, are also populated.


The results from the subject were represented in the Pharmacokinetics Concentrations (PC) domain, whereas the results from the ring were represented in the Device in Use (DU) domain, as shown in the example datasets below.

pc.xpt

RowSTUDYIDDOMAINUSUBJIDSPDEVIDPCSEQPCTESTCDPCTESTPCORRESPCORRESUPCSTRESCPCSTRESNPCSTRESUPCSPECPCDTCVISITNUMVISITPCTPTPCTPTNUMPCELTMPCTPTREFPCRFTDTC
1ABCPCABC-101RING5831DRUGADrug A200pg/mL200200pg/mLPLASMA2016-02-282VISIT 228 DAYS AFTER RING INSERTION1P28DRING 1 INSERTION2016-02-01
2ABCPCABC-101RING5842DRUGADrug A264pg/mL264264pg/mLPLASMA2016-03-263VISIT 328 DAYS AFTER RING INSERTION1P28DRING 2 INSERTION2016-02-28
3ABCPCABC-101RING5853DRUGADrug A50pg/mL5050pg/mLPLASMA2016-04-104VISIT 428 DAYS AFTER RING INSERTION1P28DRING 3 INSERTION2016-03-26

du.xpt

RowSTUDYIDDOMAINSPDEVIDDUSEQDUTESTCDDUTESTDUORRESDUORRESUDUSTRESCDUSTRESNDUSTRESUDUDTCVISITNUMVISITDUTPTDUTPTNUMDUELTMDUTPTREFDURFTDTC
1ABCDURING5831DRUGAAMTDrug A Amount6.345mg6.3456.345mg2016-02-282VISIT 228 DAYS AFTER RING INSERTION1P28DRING 1 INSERTION2016-02-01
2ABCDURING5841DRUGAAMTDrug A Amount3.557mg3.5573.557mg2016-03-263VISIT 328 DAYS AFTER RING INSERTION1P28DRING 2 INSERTION2016-02-28
3ABCDURING5851DRUGAAMTDrug A Amount20.083mg20.08320.083mg2016-04-104VISIT 428 DAYS AFTER RING INSERTION1P28DRING 3 INSERTION2016-03-26

In this example, an EX dataset was derived by calculating the difference between the records in DO (e.g., the drug load levels) and DU (e.g., the ring residual drug level) data, and thus the participant's exposure to Drug A. Informative metadata regarding the derivation should be provided in the SDTM Define-XML file.

This example should not be taken as regulatory guidance regarding how a sponsor should derive an EX dataset.

ex.xpt

RowSTUDYIDDOMAINUSUBJIDSPDEVIDEXSEQEXTRTEXDOSEEXDOSUEXDOSFRMEXDOSFRQEXROUTEEXSTDTCEXENDTC
1ABCEXABC-101RING5831Drug A18.633mgRINGCONTINUOUSINTRAVAGINAL2016-02-012016-02-28
2ABCEXABC-101RING5842Drug A21.297mgRINGCONTINUOUSINTRAVAGINAL2016-02-282016-03-26
3ABCEXABC-101RING5853Drug A4.892mgRINGCONTINUOUSINTRAVAGINAL2016-03-262016-04-10

6.3 Vaccines

As with any vaccine, the goal of a future vaccine against HIV will be to produce an immune response to the virus in order to prevent infection. As of the publication of this guide, no successful vaccine against HIV has been developed. There are numerous challenges to HIV vaccine development which are not discussed here, but research is ongoing. This section covers some of the topics relevant to those studies, including reactogenicity and vaccine-induced seroreactivity (VISR).

6.3.1 Reactogenicity

Vaccines are preparations containing antigenic substances capable of inducing a specific and active immunity against a disease or infection. Such immunity may then result in the reduced transmission of that disease or infection.

An important aspect of vaccine development is the assessment of the vaccine's reactogenicity. Reactogenicity refers to the property of a substance to produce an expected or common adverse reaction when introduced into the body. For the purpose of this guide, reactogenicity event refers to a specific expected or common reaction following vaccine administration. In vaccine studies, reactogenicity events are typically caused by an inflammatory response to the vaccine under study and may include reactions such as fever or redness at the site of administration. Reactogenicity describes immediate, short-term reactions to vaccines, not long-term sequelae.

For guidance on how to represent vaccine reactogenicity events for HIV, please refer to the Vaccines Therapeutic Area User Guide v1.1 (https://www.cdisc.org/standards/therapeutic-areas/vaccines).

6.3.2 Immune Response

Vaccines against HIV infection may be designed to raise antibodies against a number of specific epitopes on various HIV antigens. Measuring antibody titer would be one way to assess vaccine response in HIV vaccine trials.

Data about immune response to vaccines would be represented in the Immunogenicity Specimen Assessment (IS) domain.

For examples illustrating how to represent immune titers in response to vaccines, see the Virology Therapeutic Area User Guide v2.1 (https://www.cdisc.org/standards/therapeutic-areas/virology). Implementers should be aware that terminology specific to the titers they are performing may not yet be developed, and that new terminology can be requested using the New Term Request feature on the National Cancer Institute Enterprise Vocabulary Services website (https://www.cancer.gov/research/resources/terminology/cdisc).

For examples of anti-HIV antibody-specific terminology requested as part of this document, see the mb.xpt example within Section 6.3.3, Vaccine-induced Seroreactivity, Example 1.

6.3.3 Vaccine-induced Seroreactivity

Although no vaccine for HIV has been successful at the time of publication of this guide, multiple studies have been and continue to be conducted. In the post-vaccine world of HIV testing, an additional possible outcome to be considered is VISR. This outcome results from having been exposed to certain HIV antigens through a vaccine, as opposed to having been exposed to the actual virus. Given the stigma associated with HIV-positive status, it is important to distinguish between true positivity and seropositivity due to vaccine exposure.

The following concept map depicts a widely accepted algorithmic approach to determining HIV status, with considerations for interpreting results within the context of prior HIV vaccination.

Concept Map. Vaccine-induced Seroreactivity

Example

In this hypothetical example, a subject participating in a vaccine trial received an HIV vaccine at the start of the study (data not shown) and was instructed to return for routine HIV testing. At the Week 6 visit, the subject tested positive for an HIV-1/2 antibody test and participated in additional confirmatory tests in accordance with the algorithm depicted in the preceding concept map. This ultimately led to the conclusion that the subject was HIV negative and had experienced vaccine-induced seroreactivity. Note that the second stage confirmatory test could also have been a western blot. In this case, the data would be handled the same: Individual antibodies tested for would be represented in ISTEST, but the method would be "WESTERN BLOT".

Rows 1-9:The combination of ISTESTCD/ISTEST and ISTSTDTL indicate that these tests are looking for the presence of the microbial-induced antibodies against the antigens identified in the non-standard variable ISBDAGNT.
Rows 1-3:Show the subject was tested with 3 separate enzyme immunoassay tests for HIV and tested positive on 2 and indeterminate on the other. These tests detect the presence of antibodies against HIV-1 and -2 but do not differentiate which virus antibodies were detected.
Rows 4-9:Show the results from a confirmatory immunochromatographic assay that detects antibodies to specific antigens from both HIV-2 (Rows 4-5) and HIV-1 (Rows 6-9). SPDEVID indicates that details about this assay are available in the Device Identifiers (DI) domain. Note that 2 distinct HIV-1 antibodies were detected (Rows 6 and 9).
Row 10:Shows the subject is HIV-2 negative according to the assay identified in SPDEVID. The sponsor has chosen to group this interpretation record via ISGRPID to the 2 records from the assay that are relevant to HIV-2 antibody detection.
Row 11:Shows the subject is HIV-1 positive according to the assay identified in SPDEVID. The sponsor has chosen to group this interpretation record via ISGRPID to the 4 records from the assay that are relevant to HIV-1 antibody detection.

is.xpt

RowSTUDYIDDOMAINUSUBJIDISSEQSPDEVIDISGRPIDISTESTCDISTESTISTSTDTLISORRESISSTRESCISSPECISMETHODVISITNUMVISITISDTC
ISBDAGNT
1ABCISABC-0041EIA01
MBABBinding Microbial-induced AntibodyDETECTIONDETECTEDDETECTEDBLOODEIA3WEEK 62017-05-22
HIV-1/2 Antigen
2ABCISABC-0042EIA02
MBABBinding Microbial-induced AntibodyDETECTIONINDETERMINATEINDETERMINATEBLOODEIA3WEEK 62017-05-22
HIV-1/2 Antigen
3ABCISABC-0043EIA03
MBABBinding Microbial-induced AntibodyDETECTIONDETECTEDDETECTEDBLOODEIA3WEEK 62017-05-22
HIV-1/2 Antigen
4ABCISABC-0044001051MBABBinding Microbial-induced AntibodyDETECTIONNOT DETECTEDNOT DETECTEDSERUMIMMUNOCHROMATOGRAPHY3WEEK 62017-05-22
HIV-2 GP36 Antigen
5ABCISABC-0045001051MBABBinding Microbial-induced AntibodyDETECTIONNOT DETECTEDNOT DETECTEDSERUMIMMUNOCHROMATOGRAPHY3WEEK 62017-05-22
HIV-2 GP140 Antigen
6ABCISABC-0046001052MBABBinding Microbial-induced AntibodyDETECTIONDETECTEDDETECTEDSERUMIMMUNOCHROMATOGRAPHY3WEEK 62017-05-22
HIV-1 P31 Antigen
7ABCISABC-0047001052MBABBinding Microbial-induced AntibodyDETECTIONNOT DETECTEDNOT DETECTEDSERUMIMMUNOCHROMATOGRAPHY3WEEK 62017-05-22
HIV-1 GP160 Antigen
8ABCISABC-0048001052MBABBinding Microbial-induced AntibodyDETECTIONNOT DETECTEDNOT DETECTEDSERUMIMMUNOCHROMATOGRAPHY3WEEK 62017-05-22
HIV-1 P24 Antigen
9ABCISABC-0049001052MBABBinding Microbial-induced AntibodyDETECTIONDETECTEDDETECTEDSERUMIMMUNOCHROMATOGRAPHY3WEEK 62017-05-22
HIV-1 GP41 Antigen
10ABCISABC-00410001051HIV2SRHIV-2 SeroreactivityINTERPRETATIONNEGATIVENEGATIVESERUMIMMUNOCHROMATOGRAPHY3WEEK 62017-05-22

11ABCISABC-00411001052HIV1SRHIV-1 SeroreactivityINTERPRETATIONPOSITIVEPOSITIVESERUMIMMUNOCHROMATOGRAPHY3WEEK 62017-05-22

IS NSV Metadata

The final confirmatory test uses PCR to detect HIV RNA in the subject sample. This example shows that HIV RNA was not detected in the sample, and the subject is therefore HIV negative. Because this assay is not based on immune response, it is represented in the Microbiology Specimen (MB) domain rather than the Immunogenicity Specimen Assessments (IS) domain.

mb.xpt

RowSTUDYIDDOMAINUSUBJIDMBSEQMBTESTCDMBTESTMBTSTDTLMBORRESMBSTRESCMBSPECMBMETHODVISITNUMVISITMBDTC
1ABCMBABC-0041HIV1RNAHIV-1 RNADETECTIONNOT DETECTEDNOT DETECTEDBLOODQUANTITATIVE REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION3WEEK 62017-05-22

Based on the fact that no viral RNA was found in the subject sample and the subject was not taking prophylactic antiretroviral therapy (prohibited by protocol), the investigator concluded the subject had developed vaccine-induced seroreactivity. This event was recorded and represented in the Clinical Events (CE) domain.

ce.xpt

RowSTUDYIDDOMAINUSUBJIDCESEQCETERMVISITNUMVISITCEDTC
1ABCCEABC-0041Vaccine-induced seroreactivity3WEEK 62017-05-22

Identifying information about the assay devices is represented in the Device Identifiers (DI) domain.

Rows 1-3:Show the device type, manufacturer, and trade name of the HIV EIA diagnostic test identified as SPDEVID="EIA01".
Rows 4-6:Show the device type, manufacturer, and trade name of the HIV EIA diagnostic test identified as SPDEVID="EIA02".
Rows 7-9:Show the device type, manufacturer, and trade name of the HIV EIA diagnostic test identified as SPDEVID="EIA03".
Rows 10-12:Show the device type, manufacturer, and trade name of the confirmatory supplemental assay identified as SPDEVID="00105".

di.xpt

RowSTUDYIDDOMAINSPDEVIDDISEQDIPARMCDDIPARMDIVAL
1ABCDIEIA011DEVTYPEDevice TypeHIV1/2 EIA Kit
2ABCDIEIA012MANUFManufacturerAcme
3ABCDIEIA013TRADENAMTrade NameImmunowise XR
4ABCDIEIA021DEVTYPEDevice TypeHIV1/2 EIA Kit
5ABCDIEIA022MANUFManufacturerEnzyPro
6ABCDIEIA023TRADENAMTrade NameDxMate HIV
7ABCDIEIA031DEVTYPEDevice TypeHIV1/2 EIA Kit
8ABCDIEIA032MANUFManufacturerXCelerate Dx
9ABCDIEIA033TRADENAMTrade NameXCel-RNA
10ABCDI001051DEVTYPEDevice TypeHIV supplemental assay system
11ABCDI001052MANUFManufacturerBio-Rad
12ABCDI001053TRADENAMTrade NameGeenius HIV 1/2 Supplemental Assay System

There is no RELREC dataset included as part of this example. The sponsor could have used this dataset to create a link from the records in MB and IS with the diagnosis record in CE. For more information on creating RELREC datasets, see SDTMIG Section 8.2, Relating Peer Records .

7 Disease Assessments

This section generally provides information on data used to evaluate how a subject is progressing over the course of a study. These data are typically collected multiple times during the study. However, this section includes an example (Section 7.1, CD4 Counts) illustrating the representation of both pre- and on-study CD4 counts. While pre-study CD4 counts would generally be represented in Section 3, Subject and Disease Characteristics, for clarity they are shown together in this section with on-study assessments.

7.1 CD4 Counts

CD4 counts are an important lab result to collect for HIV-infected people. In addition to determining CD4 counts during a study, subjects are often asked about their nadir (i.e., lowest) CD4 count. The source of the nadir CD4 count may be a subject's medical records, but may also be based on subject recall. Since a subject may not be able to recall an exact number, nadir CD4 count may be collected using ranges, rather than an exact value.

Example

The representation of both historical and on-study CD4 counts is shown for one subject at a screening visit. A sample was collected, the CD4 count was determined and electronically reported by a central lab (i.e., a case report form was not completed). The subject was also asked several questions about lifetime nadir (lowest) CD4 count and the responses were recorded on the case report form shown below.

The Nadir CD4 CRF was used to solicit information about a subject's historical lowest CD4 count obtained by medical records and subject recall. In this example CRF, the following syntax was used to create denormalized CDASH variable names: SPONSOR DEFINED NAME_TESTCD_ROOT VARIABLE.

Historical Nadir CD4 CRF

LBCAT Hidden/pre-populated
HEMATOLOGY HISTORY
Indicate if there are any CD4+ absolute counts with source documentation available. If Yes, include the appropriate details where indicated on the CRF.Were there CD4+ absolute counts with source documentation?
DOC_CD4_LBYN Not submitted

<From NY codelist>

Record the lowest CD4+ absolute count in cells/uL for which there is source documentation.
DOC_CD4_LBORRES LBORRES
_____
DOC_CD4_LBORRESU LBORRESU Pre-populated
10^6/L

<From UNIT codelist>

DOC_CD4_LBSOURCE NSV.LBSOURCE Hidden/pre-populated
MEDICAL RECORD
DOC_CD4_LBCOLSRT NSV.LBCOLSRT Hidden/pre-populated
LOWEST
Record the date of specimen collection according to the source documentation.
DOC_CD4_LBDAT LBDTC
_ _ / _ _ _ / _ _ _ _
Indicate whether the subject recalls a different lowest CD4+ absolute count for which there is no source documentation. If Yes, include the appropriate details where indicated on the CRF.Does the subject recall a lower CD4+ absolute count than is in the source documentation?
RECALL_CD4_LBYN Not submitted

<From NY codelist>

Record the subject-recalled lowest CD4+ count in cells/uL.Result
RECALL_CD4_LBORRES LBORRES
RECALL_CD4_LBORRESU LBORRESU Pre-populated
10^6/L

<From UNIT codelist>

RECALL_CD4_LBCOLSRT NSV.LBCOLSRT Hidden/pre-populated
LOWEST
RECALL_CD4_LBSOURCE NSV.LBSOURCE Hidden/pre-populated
SUBJECT RECALL
CRF Metadata
Order NumberTAUG ReferenceCDASH Variable NameCDASHIG Variable LabelQuestion TextPromptData TypeCase Report Form Completion InstructionsMaps to the SDTMIG VariableSDTM Variable Mapping InstructionsControlled Terminology CodeList NameCRF Implementation NotesPermissible ValuesPre-specified ValuesQuery DisplayHidden?
1TAUG-HIV v1.0LBCATCategory for Lab TestWhat was the name of the lab panel?HEMATOLOGYtext
LBCAT



HEMATOLOGY HISTORYpromptY
2TAUG-HIV v1.0DOC_CD4_LBYNAny CD4+ absolute counts with source docWere there CD4+ absolute counts with source documentation?Any CD4+ absolute countstextIndicate if there are any CD4+ absolute counts with source documentation available. If Yes, include the appropriate details where indicated on the CRF.

(NY)
Yes; No
question
3TAUG-HIV v1.0DOC_CD4_LBORRESResultWhat was the result of the lab test?ResultintegerRecord the lowest CD4+ absolute count in cells/uL for which there is source documentation.LBORRESLBORRES where LBTESTCD="CD4"
The CDASH variable names indicate what type of CD4 information is collected. When represented in SDTM, the --TESTCD is "CD4".

prompt
4TAUG-HIV v1.0DOC_CD4_LBORRESUUnitWhat was the unit of the lab result?Unittext
LBORRESU
(UNIT)

10^6/Lprompt
5TAUG-HIV v1.0DOC_CD4_LBSOURCESourceWhat was the source of the lab result?Source of DatatextN/ANSV.LBSOURCE



MEDICAL RECORDpromptY
6TAUG-HIV v1.0DOC_CD4_LBCOLSRTCollected Summary Result TypeWhat was the collected summary result type?Collected Summary Result Typetext
NSV.LBCOLSRT



LOWESTpromptY
7TAUG-HIV v1.0DOC_CD4_LBDATDate of Specimen CollectionWhat was the date of lab specimen collection?Collection DatedateRecord the date of specimen collection according to the source documentation.LBDTC




prompt
8TAUG-HIV v1.0RECALL_CD4_LBYNAny CD4+ absolute countsDoes the subject recall a lower CD4+ absolute count than is in the source documentation?Any CD4+ absolute countstextIndicate whether the subject recalls a different lowest CD4+ absolute count for which there is no source documentation. If Yes, include the appropriate details where indicated on the CRF.

(NY)
Yes; No
question
9TAUG-HIV v1.0RECALL_CD4_LBORRESResultWhat was the result of the lab test?ResulttextRecord the subject-recalled lowest CD4+ count in cells/uL.LBORRESLBORRES where LBTESTCD="CD4" and LBSTRF="BEFORE"
The CDASH variable names indicate what type of CD4 information is collected. When represented in SDTM, the LBTESTCD is "CD4". As the date of collections, is not collected, a relative timing variable was used to indicate that this result was "BEFORE" the start of treatment.<50; 51-199; 200-349; 350-500; >500
prompt
10TAUG-HIV v1.0RECALL_CD4_LBORRESUUnitWhat was the unit of the lab result?UnittextN/ALBORRESULBORRESU where LBTESTCD="CD4"(UNIT)

10^6/Lprompt
11TAUG-HIV v1.0RECALL_CD4_LBCOLSRTCollected Summary Result TypeWhat was the collected summary result type?Collected Summary Result TypetextN/ANSV.LBCOLSRT



LOWESTpromptY
12TAUG-HIV v1.0RECALL_CD4_LBSOURCESourceWhat was the source of the lab result?Source of DatatextN/ANSV.LBSOURCE



SUBJECT RECALLpromptY

It is important to be able to distinguish pre-study nadir CD4 counts from CD4 counts collected during the study. In this example, nadir CD4 values can be recognized by:

  • Timing variables that indicate that the finding was pre-study
    • If the date of the nadir value is available, LBDY will be present and be negative
    • If a date of the nadir is not available, the relative timing variable LBSTRF have the value of "BEFORE", showing that the test was conducted before the study reference period
  • The presence of the variable "Lab Category" (LBCAT), with a value of "HEMATOLOGY HISTORY"
  • The presence of the NSV "Source of Data" (LBSOURCE), with values such as "MEDICAL RECORD" or "SUBJECT RECALL"

In this example, the visit variables are populated for all the data collected at the screening visit. The inclusion of the visit variables in the records for nadir CD4 values is intended to represent the fact that the data were collected at this visit, not that the tests were conducted at the screening visit.

Programs used to derive Study Visit (SV) datasets from visit dates in records for collected data should be written so as not to include pre-study dates for assessments collected at screening. One strategy may be to exclude dates prior to the date of informed consent.

This example shows data for a study subject. If the data were about an associated person, the data would be represented in the APLB domain and the dataset would include APID, RSUBJID, and SREL, rather than USUBJID.

Row 1:Shows the CD4 count of the subject on Study Day 1, as reported by Laboratory A. Note that the name of the laboratory vendor used was represented in LBNAM,
Row 2:Shows the nadir CD4 count before the start of the study, as determined by a review of the available medical records. LBDTC represents the specimen collection date associated with the nadir CD4 , which in this case was 989 days before the start of the study.. The non-standard qualifier LBCOLSRT indicates that this value represents a nadir CD4 count ("LOWEST"). The non-standard qualifier LBSOURCE provides the information that this value came from the subject's medical record. The variable LBEVINTX is populated with "LIFETIME" to indicate the evaluation period.
Row 3:Shows that the subject recalled a different nadir CD4 count than that provided by the source documentation. The subject's recalled nadir CD4 count was reported as a range, rather than a value, and the source was "SUBJECT RECALL" (LBSOURCE). The variable LBDTC is not populated, as the date of specimen collection for the subject's recalled CD4 test was not collected. Instead, LBSTRF (Start Relative to Reference Period) is populated with the value of "BEFORE" to show that this is a pre-study value. The non-standard qualifier LBCOLSRT indicates that this value represents a nadir CD4 count ("LOWEST" ). The variable LBEVINTX is populated with "LIFETIME" to indicate the evaluation period.

lb.xpt

RowSTUDYIDDOMAINUSUBJIDLBSEQLBREFIDLBTESTCDLBTESTLBCATLBORRESLBORRESULBSTRESCLBSTRESNLBSTRESULBNAMVISITNUMVISITVISITDYLBDYLBDTCLBSTRFLBEVINTX
LBCOLSRTLBSOURCE
1HIV-01LBHIV-01-001112342CD4CD4HEMATOLOGY22010^6/L22022010^6/LLAB A1SCREENING112015-03-04




2HIV-01LBHIV-01-001279343CD4CD4HEMATOLOGY HISTORY21010^6/L21021010^6/L
1SCREENING1-9892012-06-18
LIFETIME
LOWESTMEDICAL RECORD-
3HIV-01LBHIV-01-0013
CD4CD4HEMATOLOGY HISTORY51-19910^6/L51-199
10^6/L
1SCREENING1

BEFORELIFETIME
LOWESTSUBJECT RECALL

LB NSV Metadata

7.2 HIV RNA Detection and Viral Load

Antiretroviral therapy can successfully reduce morbidity and mortality associated with HIV infection and can also reduce transmission of the virus. The primary measure of effective ART in HIV-positive subjects is viral suppression as indicated by a reduction in viral load over time.

Example

This example follows 1 subject through a series of viral load assessments. By the visit at Week 48, the viral load had dropped below the limit of detection. Note the use of MBTSTDTL to indicate that test of the analyte "HIV-1 RNA" was a measurement of viral load. In this example, the sponsor populated MBLOINC because it was provided by the central lab.

Row 1:Shows the HIV-1 viral load was measured as 496700 copies/mL at the baseline visit.
Rows 2-3:Show that the HIV-1 viral load continued to drop between Weeks 4 and 24.
Row 4:Shows that HIV-1 RNA was detected in the subject's sample at the Week 48 visit, but the viral load was below the lower limit of quantitation. Because this was an attempt to measure viral load, MBTSTDTL="VIRAL LOAD", even though the assessment did not result in a quantifiable result.
Row 5:Shows that the subject's HIV-1 viral load had dropped below the limit of detection by Week 72.

mb.xpt

RowSTUDYIDDOMAINUSUBJIDSPDEVIDMBSEQMBREFIDMBTESTCDMBTESTMBTSTDTLMBORRESMBORRESUMBSTRESCMBSTRESNMBSTRESUMBLOINCMBSPECMBMETHODMBLLOQMBBLFLVISITNUMVISITMBDTC
1ABCMBABC-001RT-qPCR011001-02HIV1RNAHIV-1 RNAVIRAL LOAD496700copies/mL496700496700copies/mL70241-5PLASMAQUANTITATIVE REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION20Y2BASELINE2016-05-19
2ABCMBABC-001RT-qPCR012001-03HIV1RNAHIV-1 RNAVIRAL LOAD19400copies/mL1940019400copies/mL70241-5PLASMAQUANTITATIVE REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION20
3WEEK 42016-06-10
3ABCMBABC-001RT-qPCR023001-04HIV1RNAHIV-1 RNAVIRAL LOAD79copies/mL7979copies/mL70241-5PLASMAQUANTITATIVE REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION20
4WEEK 242016-11-08
4ABCMBABC-001RT-qPCR024001-05HIV1RNAHIV-1 RNAVIRAL LOADTARGET DETECTED, BELOW LLOQ
TARGET DETECTED, BELOW LLOQ


PLASMAQUANTITATIVE REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION20
5WEEK 482017-04-06
5ABCMBABC-001RT-qPCR035001-06HIV1RNAHIV-1 RNAVIRAL LOADTARGET NOT DETECTED
TARGET NOT DETECTED


PLASMAQUANTITATIVE REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION20
6WEEK 722017-10-13

Properties of the assays used to determine viral load are represented in the device domains. In the example below, the lot numbers of the assays used changed, and the sponsor chose to keep track of this parameter. Had the lot number not been changed or had not been of interest, a single SPDEVID could have been used to link to a single set of parameters in the Device Identifiers (DI) dataset.

Rows 1-4:Show the device type, manufacturer, trade name, and lot number for the RT-qPCR kit identifed by SPDEVID="RT-qPCR01".
Rows 5-8:Show the device type, manufacturer, trade name, and lot number for the RT-qPCR kit identifed by SPDEVID="RT-qPCR02".
Rows 9-12:Show the device type, manufacturer, trade name, and lot number for the RT-qPCR kit identifed by SPDEVID="RT-qPCR03".

di.xpt

RowSTUDYIDDOMAINSPDEVIDDISEQDIPARMCDDIPARMDIVAL
1ABCDIRT-qPCR011DEVTYPEDevice TypeRT-qPCR kit
2ABCDIRT-qPCR012MANUFManufacturerAcme
3ABCDIRT-qPCR013TRADENAMTrade NameDetectPRO
4ABCDIRT-qPCR014LOTLot Number20160202013
5ABCDIRT-qPCR021DEVTYPEDevice TypeRT-qPCR kit
6ABCDIRT-qPCR022MANUFManufacturerAcme
7ABCDIRT-qPCR023TRADENAMTrade NameDetectPRO
8ABCDIRT-qPCR024LOTNUMLot Number20161101004
9ABCDIRT-qPCR031DEVTYPEDevice TypeRT-qPCR kit
10ABCDIRT-qPCR032MANUFManufacturerAcme
11ABCDIRT-qPCR033TRADENAMTrade NameDetectPRO
12ABCDIRT-qPCR034LOTNUMLot Number201708101009

7.3 Drug Susceptibility

This section covers phenotypic and genotypic resistance testing as it pertains to HIV. The following concept map illustrates these concepts at a high level that is not specific to HIV.

Concept Map. Drug Sensitivity Testing

7.3.1 Phenotypic Drug Sensitivity Testing

Phenotypic drug sensitivity testing involves culturing the virus in a cell line that is permissive to infection. This topic is covered by the Virology Therapeutic Area User Guide v2.1 (https://www.cdisc.org/standards/therapeutic-areas/virology) and no additional examples are shown here. Users should refer to the Resistance Testing section of that guide for more information and illustrative examples on modeling data from these assays.

7.3.2 Genetic Resistance Calculators and Interpretations

Genetic resistance calculators provide estimates of drug resistance or susceptibility based on what is known about the genetic variations present in specific genes within the HIV isolated from a subject sample.

Example

First, the mutations data are represented in the Pharmacogenomics/Genetics Findings (PF) domain. The example below shows what a subset of mutations might look like for mutations reported as amino acid changes in the HIV-1 reverse transcriptase gene. In a study setting, these results could be reported as nucleotide, amino acid, or codon changes and there could be many records documenting mutations across multiple genes. Every change from the consensus (reference) sequence should be represented, whether or not it contributes to the overall resistance to a drug. Note that NHOID is used to clarify that these genetic variations are viral genetic results, rather than genetic results for the subject. PFSTRESC shows the HGVS nomenclature for each variant. Row 10 shows a case where there was a mixed population of viruses with respect to the same location: those with either a change to F (Phe) or a change to V (Val), as indicated in PFORRES and PFSTRESC.

pf.xpt

RowSTUDYIDDOMAINUSUBJIDNHOIDPFSEQPFTESTCDPFTESTPFGENRIPFGENTYPPFREFSEQPFORRESPFORREFPFGENLOCPFSTRESCPFMETHODVISITNUMPFDTC
1HIV01PFHIV01-101HIV-11GENVARGenetic VariationREVERSE TRANSCRIPTASEPROTEINCONSENSUS BIV60p.(Val60Ile)NEXT GENERATION SEQUENCING22018-07-31
2HIV01PFHIV01-101HIV-12GENVARGenetic VariationREVERSE TRANSCRIPTASEPROTEINCONSENSUS BRK65p.(Lys65Arg)NEXT GENERATION SEQUENCING22018-07-31
3HIV01PFHIV01-101HIV-13GENVARGenetic VariationREVERSE TRANSCRIPTASEPROTEINCONSENSUS BND67p.(Asp67Asn)NEXT GENERATION SEQUENCING22018-07-31
4HIV01PFHIV01-101HIV-14GENVARGenetic VariationREVERSE TRANSCRIPTASEPROTEINCONSENSUS BNT69p.(Thr69Asn)NEXT GENERATION SEQUENCING22018-07-31
5HIV01PFHIV01-101HIV-15GENVARGenetic VariationREVERSE TRANSCRIPTASEPROTEINCONSENSUS BRK70p.(Lys70Arg)NEXT GENERATION SEQUENCING22018-07-31
6HIV01PFHIV01-101HIV-16GENVARGenetic VariationREVERSE TRANSCRIPTASEPROTEINCONSENSUS BEK122p.(Lys122Glu)NEXT GENERATION SEQUENCING22018-07-31
7HIV01PFHIV01-101HIV-17GENVARGenetic VariationREVERSE TRANSCRIPTASEPROTEINCONSENSUS BKT139p.(Thr139Lys)NEXT GENERATION SEQUENCING22018-07-31
8HIV01PFHIV01-101HIV-18GENVARGenetic VariationREVERSE TRANSCRIPTASEPROTEINCONSENSUS BVM184p.(Met184Val)NEXT GENERATION SEQUENCING22018-07-31
9HIV01PFHIV01-101HIV-19GENVARGenetic VariationREVERSE TRANSCRIPTASEPROTEINCONSENSUS BAT200p.(Thr200Ala)NEXT GENERATION SEQUENCING22018-07-31
10HIV01PFHIV01-101HIV-110GENVARGenetic VariationREVERSE TRANSCRIPTASEPROTEINCONSENSUS BFVT215p.(Thr215Phe^Val)NEXT GENERATION SEQUENCING22018-07-31
11HIV01PFHIV01-101HIV-111GENVARGenetic VariationREVERSE TRANSCRIPTASEPROTEINCONSENSUS BCK219p.(Lys219Cys)NEXT GENERATION SEQUENCING22018-07-31
12HIV01PFHIV01-101HIV-112GENVARGenetic VariationREVERSE TRANSCRIPTASEPROTEINCONSENSUS BHQ334p.(Gln334His)NEXT GENERATION SEQUENCING22018-07-31
13HIV01PFHIV01-101HIV-113GENVARGenetic VariationREVERSE TRANSCRIPTASEPROTEINCONSENSUS BDG335p.(Gly335Asp)NEXT GENERATION SEQUENCING22018-07-31
14HIV01PFHIV01-101HIV-114GENVARGenetic VariationREVERSE TRANSCRIPTASEPROTEINCONSENSUS BIN348p.(Asn348Ile)NEXT GENERATION SEQUENCING22018-07-31

Next, the summary report generated by the resistance calculator is represented as records in the Microbiology Susceptibility (MS) domain. Only 5 of the 14 changes in the reverse transcriptase gene represented in PF above were scored by the resistance calculator algorithm for tenofovir, the drug named in MSAGENT. A total of 6 mutations were scored for the nucleaoside reverse transicriptase inhibitor drug class. The 8 remaining unscored variants shown above presumably do not affect resistance to the drug. In this example, the sponsor chose to represent the list of scored mutations relevant to each record in the non-standard variable MSSCRMUT to match how the data were received in the output of the algorithm. RELREC could have also been used to link the resistance summary conclusions in MS with the mutations in PF.

Row 1:

Shows the resistance calculator raw score for tenofovir, based on the mutations present. MSANMETH identifies the Stanford resistance calculator as the source of this score. The non-standard variable MSSCRMUT lists all the mutations that the algorithm scored for tenofovir. MSGRPID is used to group this score record with its interpretation in Row 2.

Row 2:Shows the resistance level (Intermediate Resistance) to tenofovir as determined by the Stanford resistance calculator based on the genetic variants listed in the non-standard variable MSSCRMUT. MSGRPID groups this record with the corresponding score shown in Row 1.
Row 3:Shows that the Stanford resistance calculator algorithm identified the 6 mutations shown in the NSV MSSCRMUT as conferring some level of resistance to reverse transcriptase inhibitors at the class level. Note that MSAGENT="NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS" to indicate that this finding pertains to a drug class as opposed to an individual drug. There is no associated score or resistance level associated with this finding, as it may vary by individual drug. This record instead serves to indicate that using this class of drug with this subject may be less effective.

ms.xpt

RowSTUDYIDDOMAINUSUBJIDNHOIDMSSEQMSGRPIDMSREFIDMSTESTCDMSTESTMSTSTDTLMSAGENTMSCATMSORRESMSSTRESCMSSTRESNMSANMETHVISITNUM
MSSCRMUT
1HIV01MSHIV01-101HIV-111101-001MICROSUSMicrobial SusceptibilitySCORETENOFOVIRGENETIC RESISTANCE353535STANFORD RESISTANCE CALCULATOR V8.42
D67N,K70R,M184V,T215FV,K219C
2HIV01MSHIV01-101HIV-121101-001MICROSUSMicrobial SusceptibilityINTERPRETATIONTENOFOVIRGENETIC RESISTANCEIntermediate resistanceINTERMEDIATE RESISTANCESTANFORD RESISTANCE CALCULATOR V8.42
D67N,K70R,M184V,T215FV,K219C
3HIV01MSHIV01-101HIV-13
101-001SUSMUINDSusceptibility Score Mutations Indicator
NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORSGENETIC RESISTANCEYesY
STANFORD RESISTANCE CALCULATOR V8.42
D67N,K70R,M184V,T215FV,K219C, N348I

MS NSV Metadata

While not strictly a drug resistance calculator, an HIV-1 sequence may undergo expert interpretation. For example, the International Antiviral Association–USA (IAS–USA) Drug Resistance Mutations Group is an independent, volunteer panel of experts charged with delivering accurate, unbiased, and evidence-based information on drug resistance-associated mutations for HIV clinical practitioners.[12] This group reviews new data on HIV drug resistance to maintain a current list of mutations associated with clinical resistance to HIV-1 . This list includes mutations that may contribute to a reduced virologic response to drugs that have been approved by the FDA, as well as any drugs available in expanded access programs. While expert resistance interpretations such as IAS–USA may not provide a measure of the level of drug susceptibility, they do provide an indicator that a shift in drug susceptibility has occurred. Example 2 is based on the IAS–USA interpretation of the same mutations shown in the pf.xpt example in Example 1.

Example

This example shows resistance information (based on mutations present in a subject sample) as it would be identified by the IAS–USA expert panel. As in the case of data from the Stanford algorithm, these data are represented in MS. In this example, the sponsor chose to represent the flagged mutations present to match how the data were received. RELREC could have also been used to link the resistance summary conclusions in MS with the mutations in PF.

Row 1:

Indicates that one of the mutations present in the subject's HIV sample was flagged by the IAS-USA expert panel as being associated with susceptibility to tenofovir. The non-standard variable MSFLMUT shows the specific mutation. The NSV MSREFUN shows that the IAS-USA 2017 expert panel publication refers investigators to a "user note" pertaining to this mutation.

Row 2:

Shows that another set of mutations were flagged by the IAS-USA expert panel for conferring resistance to reverse transcriptase inhibitors at the drug class level. Note that MSAGENT="NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS" to indicate that this finding pertains to a drug class as opposed to an individual drug. Additionally, a user note from the IAS-USA 2017 list was referenced for further information.

ms.xpt

RowSTUDYIDDOMAINUSUBJIDNHOIDMSSEQMSGRPIDMSREFIDMSTESTCDMSTESTMSAGENTMSCATMSORRESMSSTRESCMSANMETHVISITNUM
MSFLMUTMSREFUN
1HIV01MSHIV01-101HIV-111101-001

FLMUTIND

Flagged Mutations Present IndicatorTENOFOVIRGENETIC RESISTANCEYesYIAS-USA 2017082
K65RUSERNOTE_I
2HIV01MSHIV01-101HIV-132101-001FLMUTINDFlagged Mutations Present IndicatorNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORSGENETIC RESISTANCEYesYIAS-USA 2017082
K65R, D67N, K70R, T215FVUSERNOTE_L

MS NSV Metadata

7.4 DXA Scans

Dual-energy X-Ray Absorptiometry (DEXA or DXA) is an imaging technique used to measure bone mineral density (BMD). The purpose of conducting DXA scan assessments in HIV is twofold:

  1. antiretroviral therapy (ART) is associated with a 2-6% decline in BMD by year 2 post-initiation of therapy, and
  2. the virus itself may cause loss of BMD.

Prevalence of osteoporosis in HIV-infected individuals may be as high as 3 times that of HIV-negative matched controls, with 30-70% greater rate of fractures.[13] In addition to measuring absolute BMD, the image analysis provided by the scanner system software also computes Z scores and T scores to show how a subject compares to the general population. The Z score is the number of standard deviations the observed result falls either above (positive Z score) or below (negative Z score) the mean observed value for population-matched controls. The T score, in BMD assessment at least, is the Z score when the control population is limited to healthy 30-year-olds.

Example

This example shows data associated with a series of DXA scans performed first at a screening visit, then every 48 weeks for 2 more visits. The measurements focus on the lumbar spine and the hip (the femoral neck), as these areas support much of the body's weight.


First, the procedure may be represented in the Procedures (PR) domain. One common reason for representing procedures in the PR domain is to represent the responses to questions about whether a planned procedure was performed.

pr.xpt

RowSTUDYIDDOMAINUSUBJIDSPDEVIDPRSEQPRTRTPRPRESPPROCCURVISITNUMVISITPRSTDTC
1ABCPRABC-01-101DX131DXA SCANYY1SCREENING2015-08-04
2ABCPRABC-01-101DX132DXA SCANYY6WEEK 482016-06-28
3ABCPRABC-01-101DX133DXA SCANYY12WEEK 962017-06-02

The results from the scan are represented in the Musculoskeletal Findings (MK) domain. The scan results represented include bone mineral density (BMD), Z score, and T score for each of 2 regions across all visits. Note the gradual reduction in BMD (and associated Z scores and T scores) over the course of 3 visits spanning approximately 2 years.

Rows 1-3:Show the subject's bone mineral density, Z score, and T score from a DXA scan of the lumbar spine at the screening visit.
Rows 4-6:Show the subject's bone mineral density, Z score, and T score from a DXA scan of the left femoral neck at the screening visit.
Rows 7-12:Show the subject's bone mineral density, Z score, and T score from a DXA scan of the same 2 regions at Week 48.
Rows 13-18:Show the subject's bone mineral density, Z score, and T score from a DXA scan of the same 2 regions at Week 96.

mk.xpt

RowSTUDYIDDOMAINUSUBJIDSPDEVIDMKSEQMKTESTCDMKTESTMKORRESMKORRESUMKSTRESCMKSTRESNMKSTRESUMKLOCMKLATMKMETHODVISITNUMVISITMKDTC
1ABCMKABC-01-101DX131BMDBone Mineral Density1.126g/cm21.1261.126g/cm2SPINE, LUMBAR
DXA SCAN1SCREENING2015-08-04
2ABCMKABC-01-101DX132BMDZBone Mineral Density Z Score0.401
0.4010.401
SPINE, LUMBAR
DXA SCAN1SCREENING2015-08-04
3ABCMKABC-01-101DX133BMDTBone Mineral Density T Score0.011
0.0110.011
SPINE, LUMBAR
DXA SCAN1SCREENING2015-08-04
4ABCMKABC-01-101DX134BMDBone Mineral Density1.131g/cm21.1311.131g/cm2FEMORAL NECKLEFTDXA SCAN1SCREENING2015-08-04
5ABCMKABC-01-101DX135BMDZBone Mineral Density Z Score0.201
0.2010.201
FEMORAL NECKLEFTDXA SCAN1SCREENING2015-08-04
6ABCMKABC-01-101DX136BMDTBone Mineral Density T Score0.019
0.0190.019
FEMORAL NECKLEFTDXA SCAN1SCREENING2015-08-04
7ABCMKABC-01-101DX137BMDBone Mineral Density1.112g/cm21.1121.112g/cm2SPINE, LUMBAR
DXA SCAN6WEEK 482016-06-28
8ABCMKABC-01-101DX138BMDZBone Mineral Density Z Score0.011
0.0110.011
SPINE, LUMBAR
DXA SCAN6WEEK 482016-06-28
9ABCMKABC-01-101DX139BMDTBone Mineral Density T-Score-0.509
-0.509-0.509
SPINE, LUMBAR
DXA SCAN6WEEK 482016-06-28
10ABCMKABC-01-101DX1310BMDBone Mineral Density1.108g/cm21.1081.108g/cm2FEMORAL NECKLEFTDXA SCAN6WEEK 482016-06-28
11ABCMKABC-01-101DX1311BMDZBone Mineral Density Z Score-0.011
-0.011-0.011
FEMORAL NECKLEFTDXA SCAN6WEEK 482016-06-28
12ABCMKABC-01-101DX1312BMDTBone Mineral Density T Score-0.102
-0.102-0.102
FEMORAL NECKLEFTDXA SCAN6WEEK 482016-06-28
13ABCMKABC-01-101DX1313BMDBone Mineral Density1.092g/cm21.0921.092g/cm2SPINE, LUMBAR
DXA SCAN12WEEK 962017-06-02
14ABCMKABC-01-101DX1314BMDZBone Mineral Density Z Score-0.502
-0.502-0.502
SPINE, LUMBAR
DXA SCAN12WEEK 962017-06-02
15ABCMKABC-01-101DX1315BMDTBone Mineral Density T-Score-0.704
-0.704-0.704
SPINE, LUMBAR
DXA SCAN12WEEK 962017-06-02
16ABCMKABC-01-101DX1316BMDBone Mineral Density1.103g/cm21.1031.103g/cm2FEMORAL NECKLEFTDXA SCAN12WEEK 962017-06-02
17ABCMKABC-01-101DX1317BMDZBone Mineral Density Z Score-0.152
-0.152-0.152
FEMORAL NECKLEFTDXA SCAN12WEEK 962017-06-02
18ABCMKABC-01-101DX1318BMDTBone Mineral Density T Score-0.313
-0.313-0.313
FEMORAL NECKLEFTDXA SCAN12WEEK 962017-06-02

The device used in the scan is identified in the PR and MK domains by the identifier SPDEVID. The Device Identifiers (DI) domain provides the identifying characteristics of this device. Capturing this information may be particularly important in imaging, where changes in the equipment used across a study can significantly affect results.

di.xpt

RowSTUDYIDDOMAINSPDEVIDDISEQDIPARMCDDIPARMDIVAL
1ABCDIDX131DEVTYPEDevice TypeDUAL-ENERGY X-RAY ABSORPTIOMETRY TOTAL BODY SCANNER
2ABCDIDX132MANUFManufacturerHOLOGIC
3ABCDIDX133MODELModelQDR-4500A

The results expressed as Z scores are based on reference equations used by the device. The reference equation used is represented in the Device In Use (DU) domain, as is the version of the software running on the scanner.

du.xpt

RowSTUDYIDDOMAINUSUBJIDSPDEVIDDUSEQDUTESTCDDUTESTDUORRES
1ABCDUABC-01-101DX131DXAREFEQDXA Reference EquationNATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY (NHANES) III 2010
2ABCDUABC-01-101DX132SFTWRVERSoftware Version16

7.5 Flow Cytometry

A CDISC subteam is currently working on examples for HIV-related flow cytometry results. This work is ongoing and is expected to be published in a future version of the SDTMIG.

7.6 Questionnaires, Ratings, and Scales

eQuestionnaires, Ratings, and Scales (QRSs) are typically done repeatedly over the course of a study. These are used to evaluate how a subject is progressing, by assessing the severity of disease and improvement or worsening of specific symptoms.


QRS measures are maintained as stand-alone guides on the CDISC website (https://www.cdisc.org/foundational/qrs). The following table lists assessments that are being pursued as potential supplements as part of the development work for the TAUG-HIV. Supplements may or may not be finalized at the time of publication of this user guide, and depend on copyright approval where applicable. CDISC cannot produce supplements for copyrighted measures without the express permission of the copyright holder.


Sponsors should refer to the link above if a measure of interest is not included below, as it may have been developed for another therapeutic area; new measures are implemented on an ongoing basis by the CDISC QRS Terminology and Standards Development subteams. Table. Measures Relevant to HIV Research

Full Name and AbbreviationCopyright Permission StatusSupplement Status
HIV Treatment Satisfaction Questionnaire Status Version 14+ (HIVTSQs)To be requested
HIV Treatment Satisfaction Questionnaire Change Version 14+ (HIVTSQc)To be requested
Perception of Injection (PIN)More information needed
HIV/AIDS-Targeted Quality of Life (HATQoL)To be requested
ACCEPTMore information needed
EQ5D/EQ5D-5LGrantedDone
CDC Classification System for HIV-Infected Adults and AdolescentsGrantedDone
World Health Organization HIV Classification SystemGrantedDone
Symptoms Distress ModuleMore information needed
Apgar Score Requested
Edinburgh Postnatal Depression StudyGrantedSupplement in progress
Short Physical Performance BatteryTo be requested
Duke Activity Status Index (DASI)To be requested
Rapid Eating Assessment for PatientsTo be requested
Gestational Age ClassificationMore information needed
Intrauterine Growth Retardation (IUGR)To be requested
Gestational Age by Exam (Ballard, Dubowitz version)To be requested
World Health Organization Quality of Life HIV BREF (WHOQoL-HIV BREF)To be requested
Center for Epidemiologic Studies Depression Scale (CESD)To be requested

8 Analysis Data

This section demonstrates the use of ADaM in HIV in a limited set of use cases:

For information and specifications for the content of datasets that should be submitted as part of an application for drugs intended to treat HIV, please refer to the FDA's HIV Technical Specifications Guidance: https://www.fda.gov/downloads/ForIndustry/DataStandards/StudyDataStandards/UCM603323.pdf .

8.1 Subject Level Analysis Data (ADSL)

The example below shows an abbreviated ADSL dataset, which includes the variables that may be of specific interest to HIV snapshot analysis. Discontinuation status and reason for discontinuation from study have been included for this purpose. Variables representing subject-level data that would commonly occur in ADSL regardless of therapeutic area (e.g., sex, race, age, age groups, geographic region, population flags, treatment start and stop date), are not shown.

Example

The following tables provide examples of an abbreviated ADSL, ADSL dataset metadata, and ADSL variable metadata. The source derivation metadata for the variables are provided for illustrative purposes and not intended to represent standard derivation logic. Additional text in the Source/Derivation/Comment column is meant to provide further discussion for the variable and would not be present in an actual define.xml document.

Example metadata at the dataset and variable level appear below.

ADSL Dataset Metadata

ADSL Variable Metadata

This is an example of the ADSL dataset.

adsl.xpt

RowSTUDYIDUSUBJIDEOSSTTDCSREASTRTSDT
1ABC-123ABC-123-001DISCONTINUEDDeath2017-02-01
2ABC-123ABC-123-002DISCONTINUEDProtocol Deviation2017-02-15
3ABC-123ABC-123-003DISCONTINUEDLack of Efficacy2017-03-02
4ABC-123ABC-123-004COMPLETED
2017-03-15

8.2 FDA Snapshot Analysis

FDA snapshot is a virologic primary efficacy endpoint analysis that is primarily based on the HIV RNA viral load at a point in time (in this example it is at 48 weeks). Patients are grouped into 3 categories for analysis based on the viral load value as well as other relevant factors (see below); the values displayed on the summary table are "<50 HIV RNA copies/mL", "≥50 copies/mL", and "No Virologic Data". Cut-off points other than 50 copies/mL may also be used.

It is important to note that the category for subjects having ≥50 copies/mL also includes patients who:

  • changed any component of background therapy to a different drug class after the first on-treatment visit; or
  • changed components of background therapy that were not permitted per protocol, or who changed any background drug in the regimen before Week 48 due to lack of efficacy; or
  • discontinued study drug or who were withdrawn from study before Week 48 due to lack of efficacy or loss of efficacy

For patients categorized as "no virologic data", the reason for lack of data should also be recorded.

More information on the snapshot analysis is available in the FDA guidance (https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm355128.pdf).

Example

This example is based on the 4 possible scenarios shown in the figure. Each scenario is represented as a subject in the ADEFF example dataset.

Figure. FDA Snapshot Analysis Scenarios

The possible values (and decodes) for AVALC are:

  • 1=Virologic success (HIV-RNA < 50 copies/mL)
  • 2a=HIV-RNA ≥ 50 copies/mL
  • 2b=Discontinued because of virologic failure
  • 2c=Discontinued because of other reasons and HIV-1 RNA at the time of discontinuation was ≥ 50 copies/mL
  • 2d=Optimized Background Therapy (OBT) changed
  • 3a=Discontinued because of adverse event or death
  • 3b=Discontinued because of other reasons and HIV-1 RNA at the time of discontinuation was < 50 copies/mL
  • 3c=Missing data during the window but on study.

These values are further categorized as 1, 2, or 3, with the corresponding definitions: 1=Virologic success, 2=Virologic failure, 3=No virologic data. For more information, see the FDA guidance for submitting clinical trial data sets (https://www.fda.gov/downloads/ForIndustry/DataStandards/StudyDataStandards/UCM603323.pdf).
Example metadata at the dataset and variable level are shown below.

ADEFF Dataset Metadata

ADEFF Variable Metadata

The following is an ADEFF dataset example. Rows 1-4 correspond with Scenarios 1-4 in the preceding figure.

adeff.xpt

RowSTUDYIDUSUBJIDPARAMPARAMCDAVISITADTADYAWTARGETAVALCAVALCAT1MCRIT1MCRIT1MLMBSTRESNMBSEQVLIWVFFLDCSREASDCSFLDCAEDTFLDCVFFLBKTCHGFL
1ABC-123ABC-123-001Snapshot Status for cut-point of 50SS50Week 48

3363a3Snapshot Table ValueNo Virologic Data

missingNDeathYYNN
2ABC-123ABC-123-002Snapshot Status for cut-point of 50SS50Week 48

3362d2Snapshot Table ValueHIV-RNA ≥ 50 copies/mL

missingNProtocol DeviationYNNY
3ABC-123ABC-123-003Snapshot Status for cut-point of 50SS50Week 482018-02-043403362b2Snapshot Table ValueHIV-RNA ≥ 50 copies/mL4046<50NLack of EfficacyYNYN
4ABC-123ABC-123-004Snapshot Status for cut-point of 50SS50Week 482018-02-2234533611Snapshot Table ValueHIV-RNA < 50 copies/mL4052<50N
NNNN

8.3 Pregnancy Outcomes Analysis

Example 1

This example deals with a scenario in which both mother and infant are considered study subjects. Most of the efficacy outcomes are based on either mother-related topics or infant-related topics. However, 1 of the outcomes is based on comparisons of mother/infant combinations.


The sample datasets are designed to support the pairwise analysis of the mother/infant as a unit. Adverse Pregnancy Outcome is determined based on events that may occur in the mother only or the infant only. These events include spontaneous abortion, fetal death, preterm delivery, or small for gestational age.


One dataset (ADOUTEVT) is designed as per ADaM basic data structure (BDS), with parameters capturing "Y"/"N" for each of the relevant components used in the calculations of the endpoint measures. The second dataset (ADOUTCOM) is designed as an ADAM OTHER, with parameters capturing "Y"/"N" for the endpoint measure. Splitting ADOUTCOM from ADOUTEVT allows for traceability from the ADOUTCOM record back to the source records from the predecessor dataset (ADOUTEVT). Capturing the record in ADOUTEVT only would cause confusion when the outcome record is based on both the mother and infant records because there is no way to determine which USUBJID value should be used in the outcome row.

Known Issue: The ADaM BDS class currently is designed to support subject-level analysis (as well as site-level analysis). However, grouping a number of subjects as an analysis unit has not been addressed. This example proposes the variable USUBJGR1 (USUBJGRy as a generic variable) to allow for the grouping of subjects for analysis purposes. This allows for the calculation of a single analysis value that is based on the data from more than one subject. Because the ADOUTCOM dataset is summarized by family based on the values across multiple subjects, a structure based on family and parameter is needed—which does not fit within the BDS definition. Therefore, it is proposed as an ADAM OTHER class of dataset.

Example metadata at the dataset and variable level for ADOUTEVT are shown below.

ADOUTEVT Dataset Metadata

ADOUTEVT Variable Metadata

This is an example of the ADOUEVT dataset.

adoutevt.xpt

USUBJGR1USUBJIDPARAMPARAMCDAVALC
FAMILY1MOTHER1Spontaneous AbortionSPONABN
FAMILY1MOTHER1Fetal DeathFETALDTHN
FAMILY1INFANT1Preterm DeliveryPTDY
FAMILY1INFANT1Small for Gestational AgeSGESTAGEY
FAMILY2MOTHER2Spontaneous AbortionSPONABN
FAMILY2MOTHER2Fetal DeathFETALDTHN
FAMILY2INFANT2Preterm DeliveryPTDN
FAMILY2INFANT2Small for Gestational AgeSGESTAGEN

Example metadata at the dataset and variable level for ADOUTCOM are shown below.

ADOUTCOM Dataset Metadata

ADOUTCOM Variable Metadata

This is an example of the ADOUTCOM dataset.

adoutcom.xpt

USUBJGR1PARAMPARAMCDAVALC
FAMILY1Adverse Pregnancy OutcomeAPOUTCOMY
FAMILY2Adverse Pregnancy OutcomeAPOUTCOMN

Appendices

Appendix A: HIV Standards Team

NameInstitution/Organization
Laura Butte, Team LeadCritical Path Institute
Amy Palmer, Team LeadCDISC
Diane CoreyCritical Path Institute
Jane DiefenbachPharmaStat
Kristine DonatyStatistical Center for HIV/AIDS Research & Prevention (SCHARP)
Carrie FryFrontier Science and Technology Research Foundation, Inc.
Nate FreimarkThe Griesser Group
Laura HovindFrontier Science and Technology Research Foundation, Inc. (FSTRF)
Minhee KangCenter for Biostatistics in AIDS Research (CBAR) (https://www.hsph.harvard.edu/cbar/)
Maura KushStatistical Center for HIV/AIDS Research & Prevention (SCHARP)
Bess LeRoyCDISC
Erin MuhlbradtNCI-EVS
Jon NevilleCDISC
Daniel OlsonCritical Path Institute
Heather RibaudoCenter for Biostatistics in AIDS Research (CBAR) (https://www.hsph.harvard.edu/cbar/)
Anthony RodgersMerck
Ed SlezingerStatistical Center for HIV/AIDS Research & Prevention (SCHARP)
Heather SprengerFrontier Science and Technology Research Foundation, Inc. (FSTRF)
Alana St. ClairCDISC
Sarah StrobinoFrontier Science and Technology Research Foundation, Inc. (FSTRF)
Diane WoldCDISC
FDA Team MembersDivision
Wendy CarterDivision of Antiviral Products
Damon DemingDivision of Antiviral Products
Wen ZengOffice of Biometrics, Division IV

Appendix B: Glossary and Abbreviations

ADaMAnalysis Data Model
ADaMIGAnalysis Data Model Implementation Guide
AIDSAcquired Immunodeficiency Syndrome
ARTAntiretroviral Therapy
ARVAntiretroviral
BMDBone Mineral Density
CDASHClinical Data Acquisition Standards Harmonization
CDCU.S. Centers for Disease Control and Prevention
CDISCClinical Data Interchange Standards Consortium
CFASTCoalition for Accelerating Standards and Therapies
CollectedRefers to information that is recorded and/or transmitted to the sponsor, including data entered by the site on CRFs/eCRFs as well as vendor data such as core lab data. This term is a synonym for captured.
Controlled TerminologyA finite set of values that represent the only allowed values for a data item. These values may be codes, text, or numeric. A codelist is one type of controlled terminology.
CRF, aCRFCase report form (sometimes called a case record form), annotated case report form. A printed, optical, or electronic document designed to record all required information to be reported to the sponsor for each trial subject.
cSDRGClinical Study Data Reviewers Guide
DEXA or DXADual-energy X-Ray Absorptiometry
DomainA collection of observations with a topic-specific commonality about a subject
EmbryoEarly stage in the prenatal development of an animal. This stage occurs from implantation until closure of the hard palate.
FetusLate stage in the prenatal development of an animal. This stage occurs from the closure of the hard palate until birth.
HIVHuman Immunodeficiency Virus
IAS–USAInternational Antiviral Association–USA
InfantA young child between 1 month and 2 years of age.
NCI EVSNational Cancer Institute Enterprise Vocabulary Services
NewbornAn infant during the first month after birth.
OBTOptimized Background Therapy
PrEPPre-exposure Prophylaxis
SDTMStudy Data Tabulation Model
SDTMIGSDTM Implementation Guide (for Human Clinical Trials)
STISexually Transmitted Infection
SubjectA participant in a study.
VISRVaccine-induced Seroreactivity

Appendix C: Non-Standard Variables

The following table lists the non-standard variables used in this document, and gives their parent domain and variable-level metadata.

Parent DomainVariableLabelSAS Data TypeXML Data TypeCodelist/Controlled TermsRoleDescriptionNotes
CE--FETNUMNumber of Fetuses/Infants in PregnancyCharinteger
Non-Standard Record Qualifier

CE, MH--CRNORDChronological OrderChartext
Non-Standard Record QualifierSpecifies one of a group of like events by its chronological order within the evaluation interval.Examples: FIRST, MOST RECENT
CE--MODTRMode of TransmissionChartext( MODTRN )Non-Standard Record QualifierIf multiple modes of transmission are collected, --MODTR is populated with "MULTIPLE" and the NSVs --MODTR1, --MODTR2, etc.Examples: VERTICAL TRANSMISSION, HORIZONTAL TRANSMISSION, SEXUAL CONTACT, BLOOD TRANSFUSION
CE--MODTR1Mode of Transmission 1Chartext(MODTRN)Non-Standard Record QualifierThis NSV is to be used if multiple modes of transmission are collected.Examples: VERTICAL TRANSMISSION, HORIZONTAL TRANSMISSION, SEXUAL CONTACT, BLOOD TRANSFUSION
CE--MODTR2Mode of Transmission 2Chartext( MODTRN )Non-Standard Record QualifierThis NSV is to be used if multiple modes of transmission are collected.Examples: VERTICAL TRANSMISSION, HORIZONTAL TRANSMISSION, SEXUAL CONTACT, BLOOD TRANSFUSION
CE, SC, PR, VS--FTINIDFetus/Infant IdentifierChartext
Non-Standard Identifier

CE--SETTNGEvent SettingChartext
Non-Standard Result QualifierThe environment/setting where the event occurred.
DX--INSROLRole of Person who Inserted the DeviceChartext(EVAL)Non-Standard Record Qualifier

DX--RMVROLRole of Person who Removed the DeviceChartext( EVAL )Non-Standard Record Qualifier

DX--RNSINDDevice Rinsed IndicatorChartext(NY)Non-Standard Record Qualifier

IS--BDAGNTBinding AgentChartext
Non-Standard Record QualifierVariable qualifier of --TEST and --TESTCD. Used to indicate that there is a binding relationship between the entities in the --TEST and --BDAGNT variables, regardless of direction.This is proposed as a Findings Class variable.
LB--COLSRTCollected Summary Result TypeChartext
Non-Standard Record QualifierVariable qualifier of --TESTCD and --TEST. Used to indicate the type of collected summary result (e.g., MAXIMUM, MINIMUM, MEAN, MEDIAN, NADIR).This includes source summary results collected on a CRF or provided by an external vendor (e.g., central lab). If the summary result is derived using individual source data records, this summary result should be represented in ADaM. If a sponsor has both a collected summary result and a derived summary result, the collected summary result should be represented in SDTM and the derived summary result should be represented in ADaM. Examples: MAXIMUM, MINIMUM, MEAN, MEDIAN, NADIR
LB--SOURCESource of DataChartext
Non-Standard Record Qualifier

MH--BLEXNTBleeding ExtentChartext
Non-Standard Record QualifierThe bleeding extent of the menstrual flow.Examples: MILD, MODERATE, SEVERE
ML--REASOCReason for Occurrence ValueChartext
Non-Standard Record Qualifier

MS--FLMUTList of All Mutations FlaggedChartext
Non-Standard Record QualifierA comma delimited list of all mutations present in a sample that were flagged by a drug resistance algorithm.
MS--REFUNReferenced User NotesChartext
Non-Standard Record QualifierA comma delimited list of all user notes referenced by a genetic resistance algorithm or interpretation tool (e.g., IAS-USA).
MS--SCRMUTList of All Mutations ScoredChartext
Non-Standard Record QualifierA comma delimited list of all mutations present in a sample that were assigned a score according to a drug resistance calculator algorithm.
PR--BCLOCBirth Canal LocationChartext
Non-Standard Record Qualifier

PR--URGNCYProcedure Urgency Status TypeChartext(PRURGNCY)Non-Standard Record Qualifier

(Parenthesis indicates CDISC/NCI codelist)

Appendix D: References

Works Cited

  1. HIV/AIDS online Q&A. World Health Organization. http://www.who.int/features/qa/71/en. Updated November 2017. Accessed March 27, 2018.
  2. Terms, definitions, and calculations used in CDC HIV surveillance publications. Centers for Disease Control and Prevention. Updated December 12, 2016. Accessed November 29, 2018.
  3. World Health Organization. Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV. http://apps.who.int/iris/bitstream/10665/186275/1/9789241509565_eng.pdf. Published September 2015. Accessed March 27, 2018.
  4. HIV treatment, the viral reservoir, and HIV DNA. National Institute of Allergy and Infectious Diseases. https://www.niaid.nih.gov/diseases-conditions/hiv-treatment-viral-reservoir-hiv-dna. Updated March 6, 2018. Accessed March 27, 2018.
  5. HIV/AIDS: the basics. U.S. Department of Health and Human Services. https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/45/hiv-aids--the-basics. Updated November 6, 2018. Accessed November 27, 2018.
  6. About HIV/AIDS. Centers for Disease Control and Prevention. https://www.cdc.gov/hiv/basics/whatishiv.html. Updated March 16, 2018. Accessed March 27, 2018.
  7. HIV/AIDS fact sheet. World Health Organization. http://www.who.int/mediacentre/factsheets/fs360/en/. Updated November 2017. Accessed March 27, 2018.
  8. LGBTQ+ definitions. Trans Student Educational Resources. http://www.transstudent.org/definitions. Published 2018. Accessed March 27, 2018.
  9. Understanding gender. Gender Spectrum. https://www.genderspectrum.org/quick-links/understanding-gender/. Published 2017. Accessed March 27, 2018.
  10. Menstrual changes. The Well Project. http://www.thewellproject.org/hiv-information/menstrual-changes. Published September 12, 2017. Accessed March 28, 2018.
  11. US Department of Health and Human Services, Food and Drug Administration. Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs for Treatment. Guidance for Industry. Washington, DC: US Department of Health and Human Services; 2015. https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm355128.pdf. Accessed November 27, 2018.
  12. Drug resistance mutations in HIV-1. International Antiviral Society–USA. https://www.iasusa.org/content/drug-resistance-mutations-in-HIV. Accessed March 27, 2018.
  13. McComsey GA, Tebas P, Shane E, et al. Bone disease in HIV infection: a practical review and recommendations for HIV care providers. Clin Infect Dis. 2010;51(8):937-946. doi:10.1086/656412.

Additional Reading

Appendix E: Representations and Warranties, Limitations of Liability, and Disclaimers

CDISC Patent Disclaimers

It is possible that implementation of and compliance with this standard may require use of subject matter covered by patent rights. By publication of this standard, no position is taken with respect to the existence or validity of any claim or of any patent rights in connection therewith. CDISC, including the CDISC Board of Directors, shall not be responsible for identifying patent claims for which a license may be required in order to implement this standard or for conducting inquiries into the legal validity or scope of those patents or patent claims that are brought to its attention.

Representations and Warranties

"CDISC grants open public use of this User Guide (or Final Standards) under CDISC's copyright."

Each Participant in the development of this standard shall be deemed to represent, warrant, and covenant, at the time of a Contribution by such Participant (or by its Representative), that to the best of its knowledge and ability: (a) it holds or has the right to grant all relevant licenses to any of its Contributions in all jurisdictions or territories in which it holds relevant intellectual property rights; (b) there are no limits to the Participant's ability to make the grants, acknowledgments, and agreements herein; and (c) the Contribution does not subject any Contribution, Draft Standard, Final Standard, or implementations thereof, in whole or in part, to licensing obligations with additional restrictions or requirements inconsistent with those set forth in this Policy, or that would require any such Contribution, Final Standard, or implementation, in whole or in part, to be either: (i) disclosed or distributed in source code form; (ii) licensed for the purpose of making derivative works (other than as set forth in Section 4.2 of the CDISC Intellectual Property Policy ("the Policy")); or (iii) distributed at no charge, except as set forth in Sections 3, 5.1, and 4.2 of the Policy. If a Participant has knowledge that a Contribution made by any Participant or any other party may subject any Contribution, Draft Standard, Final Standard, or implementation, in whole or in part, to one or more of the licensing obligations listed in Section 9.3, such Participant shall give prompt notice of the same to the CDISC President who shall promptly notify all Participants.

No Other Warranties/Disclaimers. ALL PARTICIPANTS ACKNOWLEDGE THAT, EXCEPT AS PROVIDED UNDER SECTION 9.3 OF THE CDISC INTELLECTUAL PROPERTY POLICY, ALL DRAFT STANDARDS AND FINAL STANDARDS, AND ALL CONTRIBUTIONS TO FINAL STANDARDS AND DRAFT STANDARDS, ARE PROVIDED "AS IS" WITH NO WARRANTIES WHATSOEVER, WHETHER EXPRESS, IMPLIED, STATUTORY, OR OTHERWISE, AND THE PARTICIPANTS, REPRESENTATIVES, THE CDISC PRESIDENT, THE CDISC BOARD OF DIRECTORS, AND CDISC EXPRESSLY DISCLAIM ANY WARRANTY OF MERCHANTABILITY, NONINFRINGEMENT, FITNESS FOR ANY PARTICULAR OR INTENDED PURPOSE, OR ANY OTHER WARRANTY OTHERWISE ARISING OUT OF ANY PROPOSAL, FINAL STANDARDS OR DRAFT STANDARDS, OR CONTRIBUTION.

Limitation of Liability

IN NO EVENT WILL CDISC OR ANY OF ITS CONSTITUENT PARTS (INCLUDING, BUT NOT LIMITED TO, THE CDISC BOARD OF DIRECTORS, THE CDISC PRESIDENT, CDISC STAFF, AND CDISC MEMBERS) BE LIABLE TO ANY OTHER PERSON OR ENTITY FOR ANY LOSS OF PROFITS, LOSS OF USE, DIRECT, INDIRECT, INCIDENTAL, CONSEQUENTIAL, OR SPECIAL DAMAGES, WHETHER UNDER CONTRACT, TORT, WARRANTY, OR OTHERWISE, ARISING IN ANY WAY OUT OF THIS POLICY OR ANY RELATED AGREEMENT, WHETHER OR NOT SUCH PARTY HAD ADVANCE NOTICE OF THE POSSIBILITY OF SUCH DAMAGES.

Note: The CDISC Intellectual Property Policy can be found at: cdisc_policy_003_intellectual_property_v201408.pdf.