Discussion on Proposed Change to MolecularBiomarker Definition

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CLOSED - Proposed Change to MolecularBiomarker Definition (row 52)

Original Definition

DEFINITION: An individual mutation that alone or together with other mutations contributes to a medical conclusion.

EXAMPLE(S): L10I, K20R, M36I, A71V, V82T

OTHER NAME(S): Biological State

NOTE(S):

Ballot Comment

A mutation is only one type of molecular biomarker. A molecular biomarker does not have to yield a medical-level conclusion. This suggestion is similar to the NIH Biomarkers Definitions Working Group definition.

Proposed Definition

DEFINITION: An individual mutation that alone or together with other mutations contributes to a medical conclusion.

TYPO CORRECTION - PROPOSED DEFINITION IS ACTUALLY: A molecular biological characteristic that can be evaluated as an indicator of biological functions, processes, or therapeutic responses.

EXAMPLE(S): L10I, K20R, M36I, A71V, V82T <= SHOULD THESE BE CONSISTENT WITH THE EXAMPLE SCENARIO USED ACROSS ALL MOLECULAR BIOLOGY CLASSES???

OTHER NAME(S): Biological State

NOTE(S):

Proposed Disposition

Persuasive

Proposed Disposition Comment

Review proposed change with PGx SMEs to ensure change is consistent with their original use case for the concept. Also see disposition comments and recommendation on Gene item a few rows above. Should the two definitions be harmonized?

Outstanding Questions

• CDISC PGx SMEs: Is the proposed change consistent with your original use case for MolecularBiomarker?
• Anyone: Can someone provide a comprehensive, realistic and meaningful set of example values that uses the same overall scenario across all classes in the Molecular Biology sub-domain?

Responses

Lauren Becnel: The proposed definition is acceptable for genomics, but not for epigenomics and transcriptomics. Consider a change if appropriate to be more inclusive of existing CLIA-certified genetic test. DEFINITION: An individual molecular change that alone or together with other changes contributes to a medical conclusion.

For examples, I would consider including if appropriate genomic changes and give a few actionable genomic SNPs, gene expression level changes such as the relative expression level of a panel of transcripts from 23 genes in the Corus CAD coronary artery disease test (there are many others), and even some for CLIA certified tests from other ‘omics disciplines.

Q from WENDY (TYPE: DEFN & EX): The proposed definition on the wiki page was not the one Mollie provided, which was "A molecular biological characteristic that can be evaluated as an indicator of biological functions, processes, or therapeutic responses." - it was a typo on my part that I didn't put the right definition in there - have just added a correction. I think we need to get Lauren's input on Mollie's suggested definition since that was originally omitted on the wiki page. Regarding the examples, we need specific values here again - that's the overall theme of Mollie's comments on examples.

DISCUSSION 20160223: Proposed prosed definition is OK, Lauren will provide detailed text to add for examples

DISCUSSION 20160225: corrected proposed definition is more broad and more useful as the model expands over time. Examples are OK, just need to use the language from the biomarker group class: L10I, K20R, M36I, A71V, and V82T are all mutations that are associated with resistance to the drug "lndinavir". Lauren will try to find the example from Protease

Lauren Becnel, 20160226: 'L10I, K20R, M36I, A71V, and V82T are all amino acid changes resulting from genetic mutations in the HIV-1 protease protein that are associated with resistance to the drug "lndinavir".'

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