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RequestNotes

Status

Update Examples from TB-TAUG.


Remodel this assay and data in IS.

Fix modeling mistakes in the TB TAUG

Also requested by Joleen White

Status
colourGreen
titleResolved

  • Feedback from Ivan Jiang Ivan Jiang , whose study team had reviewed this example.

See his feedback in the comment section.

2023-09-07:

  •  Decision: We are not going to update the example. We will clarify in the example description that: ISCNDAGT is NOT controlled so this could be ESAT-6, CFP-10 or other peptide (instead of TB1 and TB2 Antigens). We are not suggesting that the stimulating agents used for TB IFN-y test have to be TB1/2 Antigens. This is just an example to show which variable needs to be used to populate which type of data, in order to make a meaningful and unique record. It is up to the sponsor to decide what collected value should be mapped to ISCNDAGT.
  •  
    Status
    colourYellow
    titleFollow-up Needed
    Action Item: Jordan to update example description when moving to Example Collection.


Status
colourGreen
titleResolved
Ivan: Need team review.


  • Joleen Joleen White requested to update the example as well. Questions about specimen info in this example.


Status
colourYellow
titleIn progress
Joleen: Need team review.

Warning
titleUpdates for SDTMIG 4.0

Make sure to update IS assumption #6: Measurements of cytokines, chemokines, and complement proteins should be represented in the Laboratory Test Results (LB) domain.

We need to draft a language to describe when to use IS vs MB vs LB for cytokine tests.

Status
colourGreen
titleDone
: IS assumption 6 has been updated.

We recently received this request: We recently received this request: https://loinc.org/95971-8/ --- SARS CoV-2 stimulated gamma interferon [Presence] in Blood (https://loinc.org/95971-8/). We also recieved received requests for the following LOINC codes: 95974-2, 95972-6, and 95973-4. Upon further research on all 4 LOINC codes, they are referring to the IFNg Response AssayIFN-y Release Assay (IGRA), which has been modeled in the LB domain in the both TB-TAUG.TAUGs V1 and V2.

TB-TAUG v2.0 modeling looks like the following - The IFNG Response test toward M. Tuberculosis is modeled in the LB domain, in the TB-TAUG as the following:

ELISA:

ELISPOT:

Image Modified

TB-TAUG v1.0 modeling looks like the following - 

Image Added

There are several issues concerns with this modeling:

  1. There are two ways of modeling Interferon Gamma Release Assay based on TB-TAUG V1 and V2, does V2 modeling replace V1 modeling? Are they modeling the same thing?
    • Email sent to Jon to see if V2 model is intended to replace V1 model.
    • Email from Jon 2022-07-07: I was indeed part of the team but have no recollection of this example or any of the discussions around how it evolved. However, I think it’s safest to go with TBv2; it must have been updated for a reason. I would deprecate the original TESTCD, especially if you’ve already been denying additional requests for tests following that same structure. 
  2. Where do you show that this challenge assay is done against M. Tuberculosis? - use NHOID?
  3. CP domain has developed a new standard variable called Test Condition Agent/CNDAGT, which is used to represent stimulating agents, like the values in ASSYAG above, should this variable be added to LB, or IS? CP Specification
  4. (or any microbe of interest, like SARS-CoV-2), where do you map M. Tuberculosis?
    • Map to NHOID.
  5. Interferon-Gamma Release Assay (IGRA) Lastly, Interferon-Gamma Response Assay is a classic immunological test, is it correct to map this to the LB domain ?
    1. Can we model this in the IS domain, see example dataset below.
    2. If we model this test in IS, how do we distinguish it from the INFg test in lab. Can we draw the line where if we are running a routine lab test looking for IFNg level it goes to LB vs. IFNg response test toward a specific, known bug then it goes to IS?
    as per the TB TAUGs? What recommendations do we give to our users in the future when we see a request such as: SARS-CoV-2 stimulated gamma interferon, https://loinc.org/95971-8/?
    • Model in IS, if you need to report the detailed changes in the actual levels of IFN-y or number of IFN-y secreting cells, the stimulating and control agents used in the assay, and a "summary interpretation" result of positive, negative, or indeterminate, etc. In this case, you are testing and recording the explicit changes in the subject/host's IFN-y release immune response, and this belongs in the IS domain. A derived MB record may be created to show that M. Tuberculosis is identified/detected based on the interpretation of the IS dataset.
    • or...
    • Model and report in MB ONLY, if you do NOT care or the lab does not provide you with actual details and results of the subject/host's IFN-y levels related changes. In this case, you are doing a microbial detection/identification test based on the interpretation (MBTSTDTL) of the INTERFERON GAMMA RELEASE ASSAY (MBMETHOD), see here: https://loinc.org/71773-6/.
  6. The ELISPOT LB example in the TB-TAUG V2 has an error, the unit is reported in SFC/10^6 PBMC so you are counting the number of cells that secrete IFN-y. The example had a LBTEST = interferon gamma, this is wrong, the test should be measured in Cells, and should be changed to ISTEST = Cytokine-secreting Cells, where ISMSCBCE = Interferon Gamma.


TB-TAUG v2.0 Remodel in the IS domain

Model in IS, if you need to report changes in the actual level of IFN-y or number of IFN-y secreting cells, the stimulating and control agents used in the assay, and a "summary interpretation" result of positive, negative, or indeterminate, etc. In this case, you are testing and recording the explicit changes in the IFN-y release immune response, and this belong in the IS domain.


Example 1: Measure INF-y using T-Cell ELISPOTIf we were to model this in IS:

ELISA
Dataset wrap
Dataset2
hi1styleyellow
hi1column ISBDAGNT
tableidIS table 1

Row

STUDYID

DOMAIN

USUBJID

SPDEVID

ISSEQ

ISGRPID

NHOID

ISLNKID

ISTESTCD

ISTEST

ISCNDAGT

ISMSCBCEISTSTCND

ISCNDAGT

ISTSTDTL

ISORRES

ISORRESU

ISSTRESC

ISSTRESN

ISSTRESU

ISSPEC

ISMETHOD

VISITNUMVISIT

ISDTC

1

ABC

IS

ABC-01-201

ABC002

1

1

Mycobacterium tuberculosis

IFNG

Interferon Gamma

Nil

1.3

IU/mL

1.3

1.3

IU/mL

BLOOD

A

CYKSCCL

Cytokine-secreting Cells

INTERFERON GAMMAWITHOUT STIMULATING AGENT

1

SFC/10^6 PBMC

1

1

SFC/10^6 PBMC

PERIPHERAL BLOOD MONONUCLEAR CELLS

ELISPOT

2013-08-26

2

ABC

IS

ABC-01-201

ABC002

2

1

Mycobacterium tuberculosisIFNG

Interferon Gamma

ESAT-6, CFP-10, TB 7.7

6.2

IU/mL

6.2

6.2

IU/mL

BLOOD

A

CYKSCCL

Cytokine-secreting Cells

INTERFERON GAMMAWITH STIMULATING AGENT

CFP-10


13

SFC/10^6 PBMC

13

13

SFC/10^6 PBMC

PERIPHERAL BLOOD MONONUCLEAR CELLS

ELISPOT

2013-08-26
ELISA
3ABCIS

ABC-01-201

ABC002

3

1

Mycobacterium tuberculosisIFNG

Interferon Gamma

Mitogen

0.9

IU/mL

0.9

0.9

IU/mL

BLOOD

A

CYKSCCL

Cytokine-secreting Cells

INTERFERON GAMMAWITH STIMULATING AGENTESAT-6
17

SFC/10^6 PBMC

1717

SFC/10^6 PBMC

PERIPHERAL BLOOD MONONUCLEAR CELLS

ELISPOT

2013-08-26
ELISA
4ABCIS

ABC-01-201

ABC00241
Mycobacterium tuberculosisIFNG

Interferon Gamma

Interpretation

Positive

Positive

BLOOD

ELISA

...

A

CYKSCCL

Cytokine-secreting Cells

INTERFERON GAMMAWITH STIMULATING AGENTMitogen
30SFC/10^6 PBMC3030SFC/10^6 PBMCPERIPHERAL BLOOD MONONUCLEAR CELLSELISPOT2013-08-26
5ABCIS

ABC-01-201

ABC002

5

1

A

CYKSCCL

Cytokine-secreting Cells

INTERFERON GAMMA

INTERPRETATION

POSITIVE


POSITIVE




ELISPOT

2013-08-26

Example 2: Measure INF-y using ELISA

Jordan Li When moving this example to the Example Collection for internal and public review, update the example description to mention that: ISCNDAGT is NOT controlled so this could be ESAT-6, CFP-10 or other peptide (instead of TB1 and TB2 Antigens). We are not suggesting that the stimulating agents used for TB IFN-y test have to be TB1/2 Antigens. This is just an example to show which variable needs to be used to populate which type of data, in order to make a meaningful and unique record. It is up to the sponsor to decide what collected value should be mapped to ISCNDAGT.

Dataset wrap
Dataset2
hi1styleyellow
hi1column ISBDAGNT
tableidIS table 1
NHOIDISCNDAGTSARS-CoV-2NilSARS-CoV-2

SARS-CoV-2 Antigen

(SARS-CoV-2 Spike Protein, etc.)3SARS-CoV-20.9009BLOODELISA

Row

STUDYID

DOMAIN

USUBJID

SPDEVID

ISSEQ

ISGRPID

ISLNKID

ISTESTCD

ISTEST

ISTSTCND

ISCNDAGT

ISTSTDTL

ISORRES

ISORRESU

ISSTRESC

ISSTRESN

ISSTRESU

ISSPEC

ISMETHOD

VISITNUMVISIT

ISDTC

1

ABC

ISABC1230-011

ABC-01-203

ABC001

1

1

B

IFNG

Interferon Gamma

WITHOUT STIMULATING AGENT

10.39

IU/mL1

0.3910.39

IU/mL

BLOODPLASMA

ELISA

2013-08-26

2

ABC

ISABC1230-011

ABC-01-203

ABC001

2

1

B

IFNG

Interferon Gamma

WITH STIMULATING AGENT

TB1 Antigen


6.2

IU/mL

6.26.2

IU/mL

BLOODPLASMA

ELISA

2013-08-26

3

ABC

IS

ABC1230-011

ABC-01-203

ABC001

2

1

B

IFNG

Interferon Gamma

Mitogen

WITH STIMULATING AGENT

TB2 Antigen


9.8

IU/mL

9.89.8

IU/mL

PLASMA

ELISA

2013-08-26
4ABCIS

ABC1230-011

4

1

SARS-CoV-2IFNG

Interferon Gamma

Interpretation

Positive

Positive

BLOOD

ABC-01-203

ABC001

3

1

B

IFNG

Interferon Gamma

WITH STIMULATING AGENT

Mitogen


5

IU/mL

55

IU/mL

PLASMA

ELISA

2013-08-26
5ABCIS

ABC-01-203

ABC001

4

1

B

IFNG

Interferon Gamma



INTERPRETATION

POSITIVE


POSITIVE




ELISA

2013-08-26

Example 3: Identification of Mycobacterium tuberculosis

The MB data below are derived records from the IS dataset above, the identification and diagnosis of Mycobacterium tuberculosis are interpretations based on the IFNy responses test results above.

Note: there is an existing, pre-coordinated MBTEST = M. tuberculosis IFN Gamma Response/C92241, (also from TB TAUG V1), this test will be deprecated because the modeling is incorrect. The MB/IS team will not publish tests similar to C92241 in the future, and we recommend users to model this type of tests using the below structure. Please be aware that you may also ONLY report the MB records below alone, if you do not care or the lab does not provide you with the actual results and details of the subject's IFN-y levels related changes. 

Dataset wrap
Namemb
Dataset2
hi1styleyellow
hi1column ISBDAGNT
tableidIS table 1

Row

STUDYID

DOMAIN

USUBJID

SPDEVID

MBSEQ

MBLNKID

MBTESTCD

MBTEST

MBTSTDTL

MBORRES

MBSTRESC

MBMETHOD

MBDTC

LOINC

1

ABC

MB

ABC-01-201

ABC002

1

A

MTBMycobacterium tuberculosisINTERPRETATION

POSITIVE

POSITIVE

INTERFERON GAMMA RELEASE ASSAY2013-08-2671773-6

2

ABC

MB

ABC-01-203

ABC001

1

B

MTBMycobacterium tuberculosisINTERPRETATION

POSITIVE

POSITIVE

INTERFERON GAMMA RELEASE ASSAY2013-08-2671773-6

The RELREC dataset below shows the relationship between IS and MB.

Dataset wrap
Namerelrec
Dataset2
RowSTUDYIDRDOMAINUSUBJIDIDVARIDVARVALRELTYPERELID
1ABCISABC-01-201ISLNKIDAMANY1
2ABCMBABC-01-201MBLNIDAONE1
3ABCISABC-01-203ISLNKIDBMANY2
4ABCMBABC-01-203MBLNIDBONE2