RequestNotesStatus
Update the Influenza TUAG for this assay.Outstanding CT request since 2014. Also answer questions for Kathleen

Outstanding IS term requests from 2014 and from the Influenza TAUG require re-model of Hemagglutination Inhibition Assay Data.

Note the below example describe a use-case of prophylactic seasonal influenza vaccine study conducted in healthy subjects.

"The seasonal influenza (flu) vaccine is designed to protect against the three or four influenza viruses research indicates are most likely to spread and cause illness among people during the upcoming flu season. Flu viruses are constantly changing, so the vaccine composition is reviewed each year and updated as needed based on which influenza viruses are making people sick, the extent to which those viruses are spreading, and how well the previous season’s vaccine protects against those viruses." - CDC.

Therefore flu vaccine creation is somewhat of an educated guess and annual prediction. Healthy subjects are normally recruited and vaccinated to test for the production of anti-influenza antibodies and other protective immune responses.

For SDTMIG 3.4, and using the IS domain, detailed taxonomic names can be mapped to the OI domain, thusly liberating the ISBDAGNT variable from having to house and control sub-strain level taxonomic information.

The OI example below shows how to represent two strains of Influenza virus, Influenza B virus (B/Acre/117700/2012) and Influenza A/Michigan/45/2015, at various taxonomic and non-taxonomic levels.

Row

STUDYID

DOMAIN

NHOID

ISSEQ

OIPARMCD

OIPARM

OIVAL

1

INF1230

OI

Influenza B virus (B/Acre/117700/2012)

1

SPCIESSPECIESInfluenza B virus
2INF1230OIInfluenza B virus (B/Acre/117700/2012)2TYPETypeB
5

INF1230

OIInfluenza B virus (B/Acre/117700/2012)3GEOORIGGeographical OriginAcre
6INF1230OIInfluenza B virus (B/Acre/117700/2012)4STRAINStrain117700
7INF1230OIInfluenza B virus (B/Acre/117700/2012)5YEARCOLLYear of Collection2012
9INF1230OIInfluenza A/Michigan/45/20151SPCIESSpecies

Influenza A virus

10INF1230OIInfluenza A/Michigan/45/20152TYPETypeA
11INF1230OIInfluenza A/Michigan/45/20153GEOORIGGeographical OriginMichigan
12INF1230OIInfluenza A/Michigan/45/20154STRAINStrain45
13INF1230OIInfluenza A/Michigan/45/20155YEARCOLLYear of Collection2015

The IS example below shows how to represent data collected from running the Hemagglutination Inhibition Assay on Influenza A and B viruses. NHOIDs generated from the OI domain above are used in the IS dataset below to show that the following tests are performed against the two specific flu A and B strains. We are assessing whether or not the antibody would prevent influenza-driven Hemagglutination process. Note the OI dataset and NHOID are used to describe and identify fully the taxonomic classification and information about the two flu strains - so such details do not have to appear elsewhere in the IS dataset.

Row

STUDYID

DOMAIN

USUBJID

ISSEQ

ISREFID

NHOID

ISTESTCD

ISTEST

ISBDAGNT

ISTSTDTLISCATISSCAT

ISORRES

ISORRESU

ISSTRESC

ISSTRESN

ISSTRESU

ISSPEC

ISMETHOD

VISITNUMVISIT

ISDTC

1

INF1230

IS

INF1230-011

1

13668

Influenza B virus (B/Acre/117700/2012)

MBAB

Microbial-induced Antibody

Influenza B VirusHemagglutination Inhibition TiterVACCINE-RELATED IMMUNOGENICITYHUMORAL IMMUNITY1:40

ratio

40

40

titer

SERUM

HEMAGGLUTINATION INHIBITION ASSAY

1VISIT 1

2017-05-27

2

INF1230

IS

INF1230-011

2

13668

Influenza A/Michigan/45/2015MBAB

Microbial-induced Antibody

Influenza A Virus

Hemagglutination Inhibition TiterVACCINE-RELATED IMMUNOGENICITYHUMORAL IMMUNITY

1:80

ratio

80

80

titer

SERUM

HEMAGGLUTINATION INHIBITION ASSAY

1VISIT 1

2017-07-27

Questions and Concerns:

The use-case describes a seasonal influenza vaccine study conducted in healthy subjects, this means none of the subjects is presumably naturally infected by the influenza viral strains of interest in the study.

  1. OI domain definition indicates that OI should be used for a bug that's been identified in a study/assay or be a known reference strain. In our use-case the influenza vaccine is a prophylactic vaccination in healthy subjects. Are the Influenza strains tested for vaccine in healthy subjects considered as "known reference strains"?
    1. Jon N: Yes, this is the correct use-case for OI and the Flu strains used in seasonal vaccines are known reference strains against which you test for vaccine immunogenicity and protective effects/strength. In this case to represent complicated taxonomic information of the strains OI dataset is recommended. NHOID is a test qualifier, it is not meant to represent a result, hence NHOID should not be created as the result of an identification test. In most studies you first identify an microorganism in an infected individual first (MB) and then create a OI dataset and NHOID for the said microorganism for subsequent testing (PF, IS, MS). Similarly for prophylactic vaccine studies you would run immunodeficiency tests against a known reference strain of bug.
  2. Ine's comments: If OI doesn't work, and we don't want to control sub-strain level taxonomic INFO, can we use NSPCES from PGx and add it to the IS domain? (Note that this approach will also entail deprecation of the –NSTRN variable. –NSPCES will still be available to allow for findings based on organisms where the species name alone is sufficient, or for sorting records based on species in a co-infection study.) Variables for Identifying Pathogens
    1. Jon N: the PGx IG is being updated; both –NSTRN and –NSPCES will be deprecated in the new version of the PGx IG. They will no longer be in use for SDTM, they are still allowed in SEND. Moving forward, tests that further characterize and assess an "identified" microorganism in PF, IS MS or non-MB findings domains should use NHOID to represent the identified bug.

Consensus:
  • Team agrees to this approach

Reasons:

Prophetical vaccine studies run immunogenicity tests against "known reference microbial strains" hence this is the correct use of OI and NHOID. This approach also liberates the ISBDAGNT variable from having to represent and control sub-strain level taxonomic information.
Other Comments:

The variable ISBDAGNT is supported by two codelists: MIROORG and ISBDAGT. The MB/IS team will NOT create controlled terminology for sub-strain level microbial terms for either codelist, such as Influenza A/Michigan/45/2015, Sars-Cov-2 Omicron Variant B.1.1.529, or Escherichia coli O157:H7 str. 2009EL1449.

ISBDAGNT is used to describe/identify the microorganism in the most "basic" term and the antigenic target of the antibody (e.g.. HIV-1 GP160, Sars-CoV-2 S Protein). This variable should NOT contain detailed taxonomic information of the bug, which should be mapped to OI.