...
| Variable Short Name | Variable Long Name | Variable Description and Usage Notes | Order of the Variable | Controlled Terminology | Additional Notes |
|---|
| --SCMBCL | Secreted Molecule by Cells | Usage: This is a domain specific variable, and qualifies the ISTEST variable. Description: The textual description of the entity secreted by the cells represented in the ISTEST. The combination of ISTEST and ISSCMBCL should describe "the thing, the entity or the analyte" one is measuring, without the need of additional variables. | It is placed right after BDAGNT | No. Free-text description. |
|
| Binding Agent
| Usage: This is a domain specific variable, and qualifies the ISTEST variable. Description: The textual description of the agent that's binding to the entity in the ISTEST variable. The ISBDAGNT variable is used to indicate that there is a binding relationship between the entities in the ISTEST and ISBDAGNT variables, regardless of direction. ISBDAGNT is not a method qualifier. It should only be used when the actual interest of the measurement is the binding interaction between the two entities in ISTEST and ISBDAGNT. In other words, the combination of ISTEST and ISBDAGNT should describe "the thing, the entity or the analyte" one is measuring, without the need of additional variables. The binding agent may be, but not limited to, a test article, a portion of the test article, a related compound, an endogenous molecule, an allergen or an infectious agent. | It is placed right after ISTEST. (this is used more than SCMBCL) | Yes. Two codelists. -Microorgansim (MICROORG) -Binding Agent for Immunogenicity Assessments (ISBDAGT). |
|
--TSTOPO | Test Operational Objective | Usage: This is a domain-specific variable for LB and IS that qualifies the --TEST variable. This is a permissible variable. Description: The textual description of the high-level purpose of the test at the operational level. | It is placed right after ISTSTDTL. *When getting this ready for internal review, make sure to add TSTDTL into the IS specification table. | Yes. One codelist.
Codelist Rules: this is a non-extensible codelist and the MB SDS/CT team reserves the right to review future term request to this codelist and decide whether addition of new terms are appropriate. Controlled Terminology: -SCREEN: A test whose operational purpose is to determine the presence or absence of a substance or organism. -CONFIRM: A test whose operational purpose is to verify the presence or absence of a substance or organism. -QUANTIFY: A test whose operational purpose is to determine the amount or concentration of a substance or organism. - use-case examples for "Quantify" are: measurements of any types of antibody titer (titration), viral load, bacterial colony count, drug toxicity concentration, etc.
- drug toxicity concentration: appears often in LOINC mapping. Also see example: https://wiki.cdisc.org/x/Qx3JB
| Notes for Variable Name/Description: Analytical purpose vs operational purpose of a test - there is a difference between the two, analytical purpose is about the analyte itself - what specific analyte are you measuring, which is why in lab we tend to have the analyte name as the LBTEST - LBTEST tells the analyte of interest. The operational purpose/objective of an analyte test is to screen, confirm then quantify the analyte - this represents a different level of purpose, and operational purpose can be applied to any analyte hence it is not analyte-specific. Take ADA as an example, ISTEST = Binding Antidrug Antibody, this test tells you that you are looking for ADAs, not, for example, C-reactive proteins. The Screen, Confirm and Quantify then tell you the operational reason, the whys behind each performed ADA test. REAS (Currently NSV) : it is been proposed to name this variable as REAS/Reasons Done, or at least re-use this variable. This idea is rejected because we want to control this variable with very specific values and use-cases and REAS has been used in many TAUGs with all kinds of values. We do not want to confuse people who are already using REAS.
Controlled Terminology Notes: Is "Detection" a valid value for this codelist? We had said before that one should use "detection" when one does not know whether the test is for screening or confirmatory, however is this a synonym to screen? look at the definition for screening, how is it different from detection? Confirm is to verify the previously detected substance is present. - Sponsor feedback is that "detected" is normally reported as a result hence this value does not belong in this codelist, because both screen and confirm are to detect the analyte, they are test qualifiers.
How about "quantify to confirm", what does that mean, is this also a valid value? - Ine mentioned that sometimes you would perform a quantificaiton test to confirm the existence of a substance. In this instance you get a quantitative result which confirms the existence of the substance, from which you normally only report "Positive or Negative" as confirmation. However the PURPOSE of the test is still to confirm the substance, so even though in the process you are using a quantitative method, the high-level purpose is to confirm. In this instance, the correct TSTOPO value to use is still "CONFIRM". Quantitative is an attribute of the method.
|
Example 1: Tiered Testing of ADA
This example shows the tiered testing of antidrug antibody (ADA). Typical tiered testing scheme for ADA evaluation includes the following steps: screening, confirmatory, and "characterization". In the first tier, all evaluable samples are run in the screen assay. Samples that score positive in the screen assay are then analyzed in a confirmatory assay (tier 2). Samples that are positive for ADA in the screen and confirmatory tiers are reported as positive, while samples that are negative in either tier are reported as negative. Further tiered testing of positive samples frequently includes analysis of antibody titer and neutralizing activity. The variable "TSTOPO" has the following controlled values: SCREEN, CONFIRM and QUANTIFY to describe the operational objective or the reason behind each testing step, and also to provide uniqueness to each row of record. ISGRPID is used in this example to show that the records are related to each other, and in this case, tests are done in a tiered, sequential manner.
| Dataset wrap |
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| Rowcaps |
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| Row 1: | Shows the screening of the presence of ADA to DRUG AZ-007. | | Row 2: | Shows the confirmation of the previously detected ADA to DRUG AZ-007. | | Row 3: | Shows the quantification of the said ADA from the screen and confirmatory steps. |
|
| Dataset2 |
|---|
| Row | STUDYID | DOMAIN | USUBJID | ISSEQ | ISREFID | ISGRPID | ISTESTCD | ISTEST | ISBDAGNT | ISTSTOPO | ISCAT | ISSCAT | ISORRES | ISORRESU | ISSTRESC | ISSTRESN | ISSTRESU | ISSPEC | ISMETHOD | VISITNUM | VISIT | ISDTC |
|---|
| 1 | ABC | IS | ABC-002 | 1 | V555 | 1 | ADA_BAB | Binding Antidrug Antibody | DRUG AZ-007 | SCREEN | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | POSITIVE |
| POSITIVE |
|
| SERUM | ELECTROCHEMILUMINESCENCE IMMUNOASSAY | 1 | VISIT 1 | 2017-07-27 |
|---|
| 2 | ABC | IS | ABC-002 | 2 | V555 | 1 | ADA_BAB | Binding Antidrug Antibody | DRUG AZ-007 | CONFIRM | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | POSITIVE |
| POSITIVE |
|
| SERUM | ELECTROCHEMILUMINESCENCE IMMUNOASSAY | 1 | VISIT 1 | 2017-07-27 |
|---|
| 3 | ABC | IS | ABC-002 | 3 | V555 | 1 | ADA_BAB | Binding Antidrug Antibody | DRUG AZ-007 | QUANTIFY | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | 50 | titer | 50 | 50 | titer | SERUM | ELECTROCHEMILUMINESCENCE IMMUNOASSAY | 1 | VISIT 1 | 2017-07-27 |
|---|
|
| Nsvmeta |
|---|
|
| Variable | Label | Type | Role | Origin |
|---|
| ISTSTOPO | Test Operational Objective | text | Non-Standard Record Qualifier | CRF |
|
|
Example 2: Consolidated Reporting of ADA
The example below shows how to represent the various types of antidrug antibody tests (ADA). Of note, while most ADAs do not inhibit the pharmacodynamic activity of the drug, neutralizing antidrug antibodies (NAbs) can inhibit drug activity soon after the drug is administered. However, most ADAs, or rather, the non-NAbs can lower the drug's systemic exposure just as well by increasing the rate of drug clearance, resulting in a clinically similar outcome to that of Nabs – reduced clinical efficacy.
...
| Dataset wrap |
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| Rowcaps |
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| Rows 1-2: | Show the confirmation and quantification of binding ADA to coagulation factor VIII analogue drug. A binding antidrug antibody is an antibody that binds to a drug. | | Rows 3-4: | Show the confirmation and quantification of the neutralizing binding ADA to coagulation factor VIII analogue drug. A neutralizing binding antidrug antibody is a type of ADA that binds to the functional portion of a drug leading to diminished or negated pharmacological activity. The neutralizing ADAs are a subset of the total ADAs. | | Rows 5-6: | Show the confirmation and quantification of the cross-reactive binding ADA to the endogenous coagulation factor VIII. A cross-reactive binding antidrug antibody is a type of ADA that binds to endogenous molecules, they are also a subset of the total ADAs. | | Rows 7-8: | Show the confirmation and quantification of the neutralizing cross-reactive binding ADA to the endogenous coagulation factor VIII. A neutralizing cross-reactive binding antidrug antibody is a type of ADA that binds to endogenous molecules and diminishes or negates their function; in some cases, they may also bind and negate the function of the study drug. They are a subset of the total ADAs. |
|
| Dataset2 |
|---|
| Row | STUDYID | DOMAIN | USUBJID | ISSEQ | ISREFID | ISGRPID | ISTESTCD | ISTEST | ISBDAGNT | ISCAT | ISSCAT | ISORRES | ISORRESU | ISSTRESC | ISSTRESN | ISSTRESU | ISSPEC | ISMETHOD | VISITNUM | VISIT | ISDTC |
| ISTSTOPO |
|---|
| 1 | ABC | IS | ABC-001 | 1 | A42839 | 1 | ADA_BAB | Binding Antidrug Antibody | COAGULATION FACTOR VIII ANALOGUE DRUG | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | POSITIVE |
| POSITIVE |
|
| SERUM | ELECTROCHEMILUMINESCENCE IMMUNOASSAY | 1 | VISIT 1 | 2017-07-27 |
| CONFIRM |
|---|
| 2 | ABC | IS | ABC-001 | 2 | A42839 | 1 | ADA_BAB | Binding Antidrug Antibody | COAGULATION FACTOR VIII ANALOGUE DRUG | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | 30 | titer | 30 | 30 | titer | SERUM | ELECTROCHEMILUMINESCENCE IMMUNOASSAY | 1 | VISIT 1 | 2017-07-27 |
| QUANTIFY |
|---|
| ABC | IS | ABC-001 | 3 | A42839 | 2 | ADA_NAB | Neutralizing Binding Antidrug Antibody | COAGULATION FACTOR VIII ANALOGUE DRUG | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | POSITIVE |
| POSITIVE |
|
| SERUM | HEMAGGLUTINATION INHIBITION ASSAY | 1 | VISIT 1 | 2017-07-27 |
| CONFIRM |
|---|
| 4 | ABC | IS | ABC-001 | 4 | A42839 | 2 | ADA_NAB
| Neutralizing Binding Antidrug Antibody | COAGULATION FACTOR VIII ANALOGUE DRUG | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | 60 | titer | 60 | 60 | titer | SERUM | HEMAGGLUTINATION INHIBITION ASSAY | 1 | VISIT 1 | 2017-07-27 |
| QUANTIFY |
|---|
| 5 | ABC | IS | ABC-001 | 5 | A42839 | 3 | ADA_X | Cross-Reactive Binding Antidrug Antibody | ENDOGENOUS COAGULATION FACTOR VIII | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | POSITIVE |
| POSITIVE |
|
| SERUM | ELECTROCHEMILUMINESCENCE IMMUNOASSAY | 1 | VISIT 1 | 2017-07-27 |
| CONFIRM |
|---|
| 6 | ABC | IS | ABC-001 | 6 | A42839 | 3 | ADA_X | Cross-Reactive Binding Antidrug Antibody | ENDOGENOUS COAGULATION FACTOR VIII | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | 360 | titer | 360 | 360 | titer | SERUM | ELECTROCHEMILUMINESCENCE IMMUNOASSAY | 1 | VISIT 1 | 2017-07-27 |
| QUANTIFY |
|---|
| 7 | ABC | IS | ABC-001 | 7 | A42839 | 4 | ADA_NX | Neutralizing Cross-Reactive Binding Antidrug Antibody | ENDOGENOUS COAGULATION FACTOR VIII | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | POSITIVE |
| POSITIVE |
|
| SERUM | HEMAGGLUTINATION INHIBITION ASSAY | 1 | VISIT 1 | 2017-07-27 |
| CONFIRM |
|---|
| 8 | ABC | IS | ABC-001 | 8 | A42839 | 4 | ADA_NX | Neutralizing Cross-Reactive Binding Antidrug Antibody | ENDOGENOUS COAGULATION FACTOR VIII | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | 360 | titer | 360 | 360 | titer | SERUM | HEMAGGLUTINATION INHIBITION ASSAY | 1 | VISIT 1 | 2017-07-27 |
| QUANTIFY |
|---|
|
| Nsvmeta |
|---|
|
| Variable | Label | Type | Role | Origin |
|---|
| ISTSTOPO | Test Operational Objective | text | Non-Standard Record Qualifier | CRF |
|
|
Example 3 - ADA Reaction Against Drug Components - Breakdown Product
This example shows the production of antidrug antibody in response to both the prodrug and its active metabolite. A prodrug is a compound that, after administration, is metabolized into a pharmacologically active drug. Please note in this example, even though only confirmatory records are reported and shown, it is assumed that the screening step has also been performed.
| Dataset wrap |
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| Rowcaps |
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| Rows 1-2: | Show the confirmation and quantification of the ADA against the prodrug A. | | Rows 3-4: | Show the confirmation and quantification of the ADA against the active metabolite of the prodrug A. |
|
| Dataset2 |
|---|
| Row | STUDYID | DOMAIN | USUBJID | ISSEQ | ISREFID | ISGRPID | ISTESTCD | ISTEST | ISBDAGNT | ISCAT | ISSCAT | ISORRES | ISORRESU | ISSTRESC | ISSTRESN | ISSTRESU | ISSPEC | ISMETHOD | VISITNUM | VISIT | ISDTC |
| ISTSTOPO |
|---|
| 1 | ABC | IS | ABC-004 | 1 | J123 | 1 | ADA_BAB | Binding Antidrug Antibody | PRODRUG A | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | POSITIVE |
| POSITIVE |
|
| SERUM | ELECTROCHEMILUMINESCENCE IMMUNOASSAY | 1 | VISIT 1 | 2017-07-27 |
| CONFIRM |
|---|
| 2 | ABC | IS | ABC-004 | 2 | J123 | 1 | ADA_BAB | Binding Antidrug Antibody | PRODRUG A | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | 30 | titer | 30 | 30 | titer | SERUM | ELECTROCHEMILUMINESCENCE IMMUNOASSAY | 1 | VISIT 1 | 2017-07-27 |
| QUANTIFY |
|---|
| ABC | IS | ABC-004 | 3 | J123 | 2 | ADA_BAB | Binding Antidrug Antibody | PRODRUG A ACTIVE METABOLITE | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | POSITIVE |
| POSITIVE |
|
| SERUM | ELECTROCHEMILUMINESCENCE IMMUNOASSAY | 1 | VISIT 1 | 2017-07-27 |
| CONFIRM |
|---|
| 4 | ABC | IS | ABC-004 | 4 | J123 | 2 | ADA_BAB
| Binding Antidrug Antibody | PRODRUG A ACTIVE METABOLITE | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | 60 | titer | 60 | 60 | titer | SERUM | ELECTROCHEMILUMINESCENCE IMMUNOASSAY | 1 | VISIT 1 | 2017-07-27 |
| QUANTIFY |
|---|
|
| Nsvmeta |
|---|
|
| Variable | Label | Type | Role | Origin |
|---|
| ISTSTOPO | Test Operational Objective | text | Non-Standard Record Qualifier | CRF |
|
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Example 4 - ADA Reaction Against Drug Components: Multiple Epitopes per Molecule
The example below shows the production of antidrug antibody in response to both the study biologic drug and also to different immunogenic epitopes of the biologic drug. This also captures an example for when the tier stops at screening (interferon beta1a assay) and goes straight into NAB from there. While unusual, it reflects the flexibility of these fields to incorporate multiple options.
...
| Dataset wrap |
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| Rowcaps |
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| Row 1: | Shows the presence of ADA against the active motabolite (active interferon beta 1a portion) of peginterferon beta-1a. | | Rows 2-3: | Show the screening and confirmation of ADA against the PEG epitope portion of peginterferon beta-1a. | | Rows 4-5: | Show the presence and quantification of neutralizing ADA against the whole molecule peginterferon beta-1a. | | Row 6: | Shows the absence of ADA against the active metabolite (active interferon beta 1a portion) of peginterferon beta-1a. | | Rows 7-10: | Show the screening, confirmation and quantification of ADA against the PEG epitope portion of peginterferon beta-1a. |
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| Dataset2 |
|---|
| Row | STUDYID | DOMAIN | USUBJID | ISSEQ | ISREFID | ISTESTCD | ISTEST | ISBDAGNT | ISCAT | ISSCAT | ISORRES | ISORRESU | ISSTRESC | ISSTRESN | ISSTRESU | ISSPEC | ISMETHOD | VISITNUM | VISIT | ISDTC |
| ISTSTOPO |
|---|
| 1 | ABC | IS | ABC-007 | 1 | A1 | ADA_BAB | Binding Antidrug Antibody | ACTIVE INTERFERON BETA 1A PORTION OF PEGINTERFERON BETA1A | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | POSITIVE |
| POSITIVE |
|
| SERUM | IMMUNOASSAY | 1 | VISIT 1 | 2017-07-27 |
| SCREEN |
|---|
| ABC | IS | ABC-007 | 2 | A1 | ADA_BAB | Binding Antidrug Antibody | PEG PORTION OF PEGINTERFERON BETA1A | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | POSITIVE |
| POSITIVE |
|
| SERUM | ELISA | 1 | VISIT 1 | 2017-07-27 |
| SCREEN |
|---|
| 3 | ABC | IS | ABC-007 | 3 | A1 | ADA_BAB | Binding Antidrug Antibody | PEG PORTION of PEGINTERFERON BETA1A | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | NEGATIVE |
| NEGATIVE |
|
| SERUM | ELISA | 1 | VISIT 1 | 2017-07-27 |
| CONFIRM |
|---|
| 4 | ABC | IS | ABC-007 | 4 | A1 | ADA_NAB | Neutralizing Antidrug Antibody | PEGINTERFERON BETA1A | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | POSITIVE |
| POSITIVE |
|
| SERUM | REPORTER GENE IMMUNOASSAY | 1 | VISIT 1 | 2017-07-27 |
| SCREEN |
|---|
| 5 | ABC | IS | ABC-007 | 5 | A1 | ADA_NAB | Neutralizing Antidrug Antibody | PEGINTERFERON BETA1A | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | 4.7 | titer | 4.7 | 4.7 | titer | SERUM | REPORTER GENE IMMUNOASSAY | 1 | VISIT 1 | 2017-07-27 |
| QUANTIFY |
|---|
| 6 | ABC | IS | ABC-008 | 6 | V4 | ADA_BAB | Binding Antidrug Antibody | ACTIVE INTERFERON BETA 1A PORTION OF PEGINTERFERON BETA1A | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | NEGATIVE |
| NEGATIVE |
|
| SERUM | IMMUNOASSAY | 1 | VISIT 1 | 2017-08-27 |
| SCREEN |
|---|
| ABC | IS | ABC-008 | 7 | V4 | ADA_BAB | Binding Antidrug Antibody | PEG PORTION OF PEGINTERFERON BETA1A | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | POSITIVE |
| POSITIVE |
|
| SERUM | ELISA | 1 | VISIT 1 | 2017-08-27 |
| SCREEN |
|---|
| 8 | ABC | IS | ABC-008 | 8 | V4 | ADA_BAB | Binding Antidrug Antibody | PEG PORTION OF PEGINTERFERON BETA1A | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | POSITIVE |
| POSITIVE |
|
| SERUM | ELISA | 1 | VISIT 1 | 2017-08-27 |
| CONFIRM |
|---|
| 9 | ABC | IS | ABC-008 | 9 | V4 | ADA_BAB | Binding Antidrug Antibody | PEG PORTION OF PEGINTERFERON BETA1A | ANTIDRUG ANTIBODIES | HUMORAL IMMUNITY | 40 | titer | 40 | 40 | titer | SERUM | ELISA | 1 | VISIT 1 | 2017-08-27 |
| QUANTIFY |
|---|
|
| Nsvmeta |
|---|
|
| Variable | Label | Type | Role | Origin |
|---|
| ISTSTOPO | Test Operational Objective | text | Non-Standard Record Qualifier | CRF |
|
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Example 5 - Autoimmune Disease Diagnosis
The example below shows how to represent autoantibody data.
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| Rowcaps |
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| Rows 1-2: | Show the screening and quantification of Antinuclear Antibodies, and ISBDAGNT is not populated. This is because, If an antibody test has multiple, unclearly defined/described targets, a pre-coordinated ISTEST should be created and ISBDAGNT should not be populated. In this case extractable nuclear antigens consist of >100 different soluble cytoplasmic and nuclear antigens, the ISBDAGNT variable cannot clearly and appropriately represent the target(s) of this antibody test, therefore the pre-cooirdinated ISTEST of Antinuclear Antibodies is used. |
|---|
| Rows 3-8: | Show the screening and quantification of various Sjogren's Syndrome specific autoantibodies. |
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| Dataset2 |
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| Row | STUDYID | DOMAIN | USUBJID | ISSEQ | ISREFID | ISGRPID | ISTESTCD | ISTEST | ISBDAGNT | ISORRES | ISORRESU | ISSTRESC | ISSTRESN | ISSTRESU | ISSPEC | ISMETHOD | VISITNUM | VISIT | ISDTC |
| ISTSTOPO |
|---|
| 1 | XYZ | IS | XYZ1234 | 1 | 19283746 | 1 | ANA | Antinuclear Antibodies |
| POSITIVE |
| POSITIVE |
|
| SERUM | MULTIPLEXED BEAD BASED IMMUNOASSAY | 1 | SCREENING | 2018-06-20 |
| SCREEN |
|---|
| 2 | XYZ | IS | XYZ1234 | 2 | 19283746 | 1 | ANA | Antinuclear Antibodies |
| 340 | titer | POSITIVE | 340 | titer | SERUM | MULTIPLEXED BEAD BASED IMMUNOASSAY | 1 | SCREENING | 2018-06-20 |
| QUANTIFY |
|---|
| 3 | XYZ | IS | XYZ1234 | 1 | 19283746 | 2 | ATAB | Binding Autoantibody | SJOGRENS SS-A60 | POSITIVE |
| POSITIVE |
|
| SERUM | MULTIPLEXED BEAD BASED IMMUNOASSAY | 1 | SCREENING | 2018-06-20 |
| SCREEN |
|---|
| 4 | XYZ | IS | XYZ1234 | 2 | 19283746 | 2 | ATAB | Binding Autoantibody | SJOGRENS SS-A60 | 181 | AU/mL | 181 | 181 | AU/mL | SERUM | MULTIPLEXED BEAD BASED IMMUNOASSAY | 1 | SCREENING | 2018-06-20 |
| QUANTIFY |
|---|
| 5 | XYZ | IS | XYZ1234 | 3 | 19283746 | 3 | ATAB | Binding Autoantibody | SJOGRENS SS-A52 | POSITIVE |
| POSITIVE |
|
| SERUM | MULTIPLEXED BEAD BASED IMMUNOASSAY | 1 | SCREENING | 2018-06-20 |
| SCREEN |
|---|
| 6 | XYZ | IS | XYZ1234 | 4 | 19283882 | 3 | ATAB | Binding Autoantibody | SJOGRENS SS-A52 | 51 | AU/mL | 51 | 51 | AU/mL | SERUM | MULTIPLEXED BEAD BASED IMMUNOASSAY | 1 | SCREENING | 2018-06-20 |
| QUANTIFY |
|---|
| 7 | XYZ | IS | XYZ1234 | 5 | 19283882 | 4 | ATAB | Binding Autoantibody | SJOGRENS SS-B | POSITIVE |
| POSITIVE |
|
| SERUM | MULTIPLEXED BEAD BASED IMMUNOASSAY | 1 | SCREENING | 2018-06-20 |
| SCREEN |
|---|
| 8 | XYZ | IS | XYZ1234 | 6 | 19283882 | 4 | ATAB | Binding Autoantibody | SJOGRENS SS-B | 169 | AU/mL | 169 | 169 | AU/mL | SERUM | MULTIPLEXED BEAD BASED IMMUNOASSAY | 1 | SCREENING | 2018-06-20 |
| QUANTIFY |
|---|
|
| Nsvmeta |
|---|
|
| Variable | Label | Type | Role | Origin |
|---|
| ISTSTOPO | Test Operational Objective | text | Non-Standard Record Qualifier | CRF |
|
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Example 6 - Vaccine Studies
The example below shows how to represent data about vaccine-induced immunological responses, as well immunological data collected during the trial but are not germane to the study vaccine.
...
| Dataset wrap |
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| Rowcaps |
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Rows 1-2: | Show the screening and quantification of "Binding Microbial-induced IgG Antibody" against the Human Respiratory Syncytial virus (RSV)-epitope B at baseline, prior to the administration of the study vaccine. The ISBDAGNT value of "HUMAN RESPIRATORY SYNCYTIAL VIRUS-EPITOPE B", is the immunogenic target in the study vaccine that could potentially stimulate the production of antibodies. Note the ISCAT value here is STUDY VACCINE-INDUCED IMMUNOGENICITY, even though at this point, study vaccine has not been administered to the subject - this is done purposefully to enable the grouping of baseline and treatment measurements. |
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| Rows 3-4: | Show the screening and quantification of "Binding Microbial-induced IgG Antibody" against the Influenza A virus at baseline. Co-infection of the Human Respiratory Syncytial virus and Influenza A virus is commonly observed in patients hence baseline anti-Influenza A antibody is also measured to see if the subject suffers from influenza infection as well. Please note, since Influenza A is NOT the immunogenic target of interest in the RSV Vaccine Study, the ISCAT is therefore populated with the value "HISTORICAL INFECTION OR PREVIOUS VACCINATION". |
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Rows 5-6: | Show the titer of "Binding Microbial-induced IgG Antibody" against the RSV-epitope B post-vaccination at visit 1 and 2. These two records show the antibody titers had increased post-vaccination, presumably due to the stimulation from the RSV study vaccine. Note the ISCAT is populated with the value "VACCINE-RELATED IMMUNOGENICITY". |
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| Dataset2 |
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Row | STUDYID | DOMAIN | USUBJID | ISSEQ | ISREFID | ISGRPID | ISTESTCD | ISTEST | ISBDAGNT | ISTSTDTL | ISTSTOPO | ISCAT | ISSCAT | ISORRES | ISORRESU | ISSTRESC | ISSTRESN | ISSTRESU | ISSPEC | ISMETHOD | VISITNUM | VISIT | ISDTC |
| ISTSTOPO |
|---|
| 1 | RSV1230 | IS | RSV1230-011 | 1 | 13668 | 1 |
| Binding Microbial-induced IgG Antibody | HUMAN RESPIRATORY SYNCYTIAL VIRUS-EPITOPE B |
|
| VACCINE-RELATED IMMUNOGENICITY | HUMORAL IMMUNITY | POSITIVE |
| POSITIVE |
|
| SERUM | ELISA | 1 | BASELINE | 2017-05-27 |
| SCREEN |
|---|
| 2 | RSV1230 | IS | RSV1230-011 | 2 | 13668 | 1 |
| Binding Microbial-induced IgG Antibody | HUMAN RESPIRATORY SYNCYTIAL VIRUS-EPITOPE B |
|
| VACCINE-RELATED IMMUNOGENICITY | HUMORAL IMMUNITY | 25 | titer | 25 | 25 | titer | SERUM | ELISA | 1 | BASELINE | 2017-05-27 |
| QUANTIFY |
|---|
| 3 | RSV1230 | IS | RSV1230-011 | 1 | 13668 | 2 |
| Binding Microbial-induced IgG Antibody | INFLUENZA A VIRUS |
|
| HISTORICAL INFECTION OR PREVIOUS VACCINATION | HUMORAL IMMUNITY | POSITIVE |
| POSITIVE |
|
| SERUM | ELISA | 1 | BASELINE | 2017-05-27 |
| SCREEN |
|---|
| 4 | RSV1230 | IS | RSV1230-011 | 2 | 13668 | 2 |
| Binding Microbial-induced IgG Antibody | INFLUENZA A VIRUS |
|
| HISTORICAL INFECTION OR PREVIOUS VACCINATION | HUMORAL IMMUNITY | 120 | titer | 120 | 120 | titer | SERUM | ELISA | 1 | BASELINE | 2017-05-27 |
| QUANTIFY |
|---|
5 | RSV1230 | IS | RSV1230-011 | 1 | 13668 |
|
| Binding Microbial-induced IgG Antibody | HUMAN RESPIRATORY SYNCYTIAL VIRUS-EPITOPE B |
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| VACCINE-RELATED IMMUNOGENICITY | HUMORAL IMMUNITY | 90 | titer | 90 | 90 | titer | SERUM | ELISA | 2 | VISIT 1 | 2017-07-27 |
| QUANTIFY |
|---|
| 6 | RSC1230 | IS | RSV1230-011 | 2 | 13668 |
|
| Binding Microbial-induced IgG Antibody | HUMAN RESPIRATORY SYNCYTIAL VIRUS-EPITOPE B |
|
| VACCINE-RELATED IMMUNOGENICITY | HUMORAL IMMUNITY | 500 | titer | 500 | 500 | titer | SERUM | ELISA | 3 | VISIT 2 | 2017-08-27 |
| QUANTIFY |
|---|
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| Nsvmeta |
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| Variable | Label | Type | Role | Origin |
|---|
| ISTSTOPO | Test Operational Objective | text | Non-Standard Record Qualifier | CRF |
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Example 7: Testing of Antibody-secreting Cells
Traditional methods such as ELISA that monitor humoral immune responses after immunization or infection typically only quantify specific antibody titers in serum. These methods do not provide any information about the actual number and location of the immune cells that secrete antibodies or cytokines.
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Row 1: | Shows the total number of IgG antibody secreting cells (ASCs) from a subject’s blood sample. In this case, ISTEST = Antibody-secreting Cells, where the entity secreted by the cells in ISTEST is represented by the variable, Secreted Molecule by Cells/ISSCMBCL. | Row 2: | Shows the number of H1 specific IgG ASCs from the same subject’s blood sample. In this case, ISTEST = Antibody-secreting Cells, where the entity secreted by the cells in ISTEST is in ISSCMBCL as "IgG antibody specific to H1 antigen". | Row 3: | Shows the number of H3 specific IgG ASCs from the same subject’s blood sample. In this case, ISTEST = Antibody-secreting Cells, where the entity secreted by the cells in ISTEST is in ISSCMBCL as "IgG antibody specific to H3 antigen". |
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| Dataset2 |
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Row | STUDYID | DOMAIN | USUBJID | ISSEQ | ISREFID | ISTESTCD | ISTEST | ISSCMBCL | ISCAT | ISSCAT | ISORRES | ISORRESU | ISSTRESC | ISSTRESN | ISSTRESU | ISSPEC | ISMETHOD | ISDTC |
|---|
1 | INFL456 | IS | INF02-01 | 1 | SAMPBL0201 | ABSCCL | Antibody-secreting Cells | TOTAL IGG ANTIBODY | VACCINE-RELATED IMMUNOGENICITY | HUMORAL IMMUNITY | 2019 | SFC/10^6 PBMC | 2019 | 2019 | SFC/10^6 PBMC | PERIPHERAL BLOOD MONONUCLEAR CELL | ELISPOT | 2011-08-08 | 2 | INFL456 | IS | INF02-01 | 2 | SAMPBL0201 | ABSCCL | Antibody-secreting Cells | INFLUENZA H1-SPECIFIC IGG ANTIBODY | VACCINE-RELATED IMMUNOGENICITY | HUMORAL IMMUNITY | 626 | SFC/10^6 PBMC | 626 | 626 | SFC/10^6 PBMC | PERIPHERAL BLOOD MONONUCLEAR CELL | ELISPOT | 2011-08-08 | 3 | INFL456 | IS | INF02-01 | 3 | SAMPBL0201 | ABSCCL | Antibody-secreting Cells | INFLUENZA H3-SPECIFIC IGG ANTIBODY | VACCINE-RELATED IMMUNOGENICITY | HUMORAL IMMUNITY | 592 | SFC/10^6 PBMC | 592 | 592 | SFC/10^6 PBMC | PERIPHERAL BLOOD MONONUCLEAR CELL | ELISPOT | 2011-08-08 |
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Example 8: Testing of Cytokine-secreting Cells
The example below shows data from the vaccine study for Respiratory Syncytial Virus (RSV) where the subject is being vaccinated with a viral vector containing RSV Epitope B. Peripheral blood mononuclear cells are isolated from the the subject and are tested before (as baseline) and after vaccination in order to investigate whether the circulating PBMCs produce increasing amounts of Interferon gamma after re-stimulating with control or RSV-Epitope B in vitro.
The example below shows how to represent the quantification of cytokine-secreting cells as the number of spots per million peripheral blood mononuclear cells (PBMC) as determined by T-Cell ELISpot from a vaccine trial.
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Rows 1-2: | Show the measurement of Cytokine-secreting Cells (ISTEST) at baseline after stimulation with placebo (row 1) or RSV Epitope B (Row 2) respectively. The type of cytokine-secreting cells that is measured in this record produces Interferon Gamma, which is represented by the ISSCMBCL variable. | Rows 3-4: | Show the measurement of Cytokine-secreting Cells (ISTEST) at Visit 1 after stimulation with placebo (row 3) or RSV Epitope B (row 4) respectively. The type of cytokine-secreting cells that is measured in this record produces Interferon Gamma, which is represented by the ISSCMBCL variable. |
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Row | STUDYID | DOMAIN | USUBJID | ISSEQ | ISREFID | ISTESTCD | ISTEST | ISSCMBCL | ISTSTDTL | ISTSTOPO | ISCAT | ISSCAT | ISORRES | ISORRESU | ISSTRESC | ISSTRESN | ISSTRESU | ISSPEC | ISMETHOD | VISITNUM | VISIT | ISDTC |
| ISAGSTIM |
|---|
1 | RSV1230 | IS | RSV1230-011 | 1 | 13668 | CYKSCCL | Cytokine-secreting Cells | INTERFERON GAMMA |
|
| VACCINE-RELATED IMMUNOGENICITY | CELLULAR IMMUNITY | 5.1 | SFC/10^6 PBMC | 5.1 | 5.1 | SFC/10^6 PBMC | PERIPHERAL BLOOD MONONUCLEAR CELL | ELISPOT | 1 | BASELINE | 2017-05-27 |
| NEGATIVE CONTROL | 2 | RSV1230 | IS | RSV1230-011 | 2 | 13668 | CYKSCCL | Cytokine-secreting Cells | INTERFERON GAMMA |
|
| VACCINE-RELATED IMMUNOGENICITY | CELLULAR IMMUNITY | 40.5 | SFC/10^6 PBMC | 40.5 | 40.5 | SFC/10^6 PBMC | PERIPHERAL BLOOD MONONUCLEAR CELL | ELISPOT | 1 | BASELINE | 2017-05-27 |
| RSV-EPITOPE B | 3 | RSV1230 | IS | RSV1230-011 | 3 | 13668 | CYKSCCL | Cytokine-secreting Cells | INTERFERON GAMMA |
|
| VACCINE-RELATED IMMUNOGENICITY | CELLULAR IMMUNITY | 6.3 | SFC/10^6 PBMC | 6.3 | 6.3 | SFC/10^6 PBMC | PERIPHERAL BLOOD MONONUCLEAR CELL | ELISPOT | 2 | VISIT 1 | 2017-08-27 |
| NEGATIVE CONTROL | | 4 | RSV1230 | IS | RSV1230-011 | 4 | 13668 | CYKSCCL | Cytokine-secreting Cells | INTERFERON GAMMA |
|
| VACCINE-RELATED IMMUNOGENICITY | CELLULAR IMMUNITY | 260.5 | SFC/10^6 PBMC | 260.5 | 260.5 | SFC/10^6 PBMC | PERIPHERAL BLOOD MONONUCLEAR CELL | ELISPOT | 2 | VISIT 1 | 2017-08-27 |
| RSV-EPITOPE B |
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| Nsvmeta |
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| Variable | Label | Type | Role | Origin |
|---|
| ISAGSTIM | Antigen Stimulation | text | Non-Standard Record Qualifier | CRF |
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Example 9 - Microneutralization Assay
In vaccine studies, microneutralization assays are commonly used in vitro assays to quantify viral-specific neutralizing antibodies in the subject’s specimen that can block viral infection in vitro, and so provide output of vaccine efficacy.
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Row | STUDYID | DOMAIN | USUBJID | ISSEQ | ISREFID | ISTESTCD | ISTEST | ISBDAGNT | ISTSTDTL | ISTSTOPO | ISCAT | ISSCAT | ISORRES | ISORRESU | ISSTRESC | ISSTRESN | ISSTRESU | ISSPEC | ISMETHOD | VISITNUM | VISIT | ISDTC |
|---|
1 | RSV1230 | IS | RSV1230-011 | 1 | 13668 |
| Neutralizing Binding Microbial-induced Antibody | RESPIRATORY SYNCYTIAL VIRUS | NEUTRALIZING TITER 50% |
| VACCINE-RELATED IMMUNOGENICITY | HUMORAL IMMUNITY | 40 | titer | 40 | 40 | titer | SERUM | MICRONEUTRALIZATION ASSAY | 1 | BASELINE | 2017-05-27 | 2 | RSV1230 | IS | RSV1230-011 | 2 | 13668 |
| Neutralizing Binding Microbial-induced Antibody | RESPIRATORY SYNCYTIAL VIRUS | NEUTRALIZING TITER 50% |
| VACCINE-RELATED IMMUNOGENICITY | HUMORAL IMMUNITY | 80 | titer | 80 | 80 | titer | SERUM | MICRONEUTRALIZATION ASSAY | 2 | VISIT 1 | 2017-07-27 | 3 | RSV1230 | IS | RSV1230-011 | 3 | 13668 |
| Neutralizing Binding Microbial-induced Antibody | RESPIRATORY SYNCYTIAL VIRUS | NEUTRALIZING TITER 50% |
| VACCINE-RELATED IMMUNOGENICITY | HUMORAL IMMUNITY | 200 | titer | 200 | 200 | titer | SERUM | MICRONEUTRALIZATION ASSAY | 3 | VISIT 2 | 2017-08-27 |
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Example 10 - Opsonophagocytic Killing Assay
In vaccine trials, the opsonophagocytic killing (OPK) assay is used as a correlate for protection to measure the "functional capacities" of vaccine-induced antibodies. This in vitro assay aids selecting promising vaccines by demonstrating whether the vaccine-induced antibodies drive efficient complement deposition and subsequent opsonophagocytic killing.
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