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Evaluation of Candidate Biomarkers of Type 1 Diabetes via the Core for Assay Validation.

Speake C, Odegard JM - Biomark Insights (2015)

Bottom Line: In this model, the CAV facilitates the validation of candidate assay methods as well as qualification of proposed biomarkers for a specific clinical use in well-characterized patients.We describe here a CAV-driven pilot project aimed at identifying biomarkers that predict the rate of decline in beta cell function after diagnosis.This strategy could be a model for other collaborative biomarker development efforts in and beyond T1D.

View Article: PubMed Central - PubMed

Affiliation: Diabetes Clinical Research Program, Benaroya Research Institute, Seattle, WA, USA.

ABSTRACT
Recognizing an increasing need for biomarkers that predict clinical outcomes in type 1 diabetes (T1D), JDRF, a major funding organization for T1D research, recently instituted the Core for Assay Validation (CAV) to accelerate the translation of promising assays from discovery to clinical implementation via a process of coordinated evaluation of biomarkers. In this model, the CAV facilitates the validation of candidate assay methods as well as qualification of proposed biomarkers for a specific clinical use in well-characterized patients. We describe here a CAV-driven pilot project aimed at identifying biomarkers that predict the rate of decline in beta cell function after diagnosis. In a formalized pipeline, candidate assays are first assessed for general rationale, technical precision, and biological associations in a cross-sectional cohort. Those with the most favorable characteristics are then applied to placebo arm subjects of T1D intervention trials to assess their predictive correlation with beta cell function. We outline a go/no-go process for advancing candidate assays in a defined qualification pipeline that also allows for the discovery of novel predictive biomarker combinations. This strategy could be a model for other collaborative biomarker development efforts in and beyond T1D.

No MeSH data available.


Related in: MedlinePlus

Blinded replication as initial validation step. Each assay is issued triplicate aliquots from a single blood draw from five individual subjects. These 15 samples are assayed in a blinded fashion. CAV staff unblind the data and calculate CV for each subject. Some assays will have multiple analytes assessed in this same manner.
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f2-bmi-suppl.4-2015-019: Blinded replication as initial validation step. Each assay is issued triplicate aliquots from a single blood draw from five individual subjects. These 15 samples are assayed in a blinded fashion. CAV staff unblind the data and calculate CV for each subject. Some assays will have multiple analytes assessed in this same manner.

Mentions: The first laboratory-based step is an evaluation of the technical precision of the assay to ensure a minimum level of reliability of the outcome, using defined samples provided by the CAV. Precision is assessed by having the investigator measure, in a blinded fashion, three or more biological replicate aliquots from the same blood draw from five or more subjects (Fig. 2). For each assay, appropriate statistical measures of variability are calculated, most commonly the coefficient of variation (CV). The CV standard selected for this pilot project was 30%. Assays with CVs >30% can repeat replicate testing or modify their assays to improve precision; the CAV can help with either of these possibilities, but assays will not advance to Cohort 1 without acceptable CV characteristics.


Evaluation of Candidate Biomarkers of Type 1 Diabetes via the Core for Assay Validation.

Speake C, Odegard JM - Biomark Insights (2015)

Blinded replication as initial validation step. Each assay is issued triplicate aliquots from a single blood draw from five individual subjects. These 15 samples are assayed in a blinded fashion. CAV staff unblind the data and calculate CV for each subject. Some assays will have multiple analytes assessed in this same manner.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4589091&req=5

f2-bmi-suppl.4-2015-019: Blinded replication as initial validation step. Each assay is issued triplicate aliquots from a single blood draw from five individual subjects. These 15 samples are assayed in a blinded fashion. CAV staff unblind the data and calculate CV for each subject. Some assays will have multiple analytes assessed in this same manner.
Mentions: The first laboratory-based step is an evaluation of the technical precision of the assay to ensure a minimum level of reliability of the outcome, using defined samples provided by the CAV. Precision is assessed by having the investigator measure, in a blinded fashion, three or more biological replicate aliquots from the same blood draw from five or more subjects (Fig. 2). For each assay, appropriate statistical measures of variability are calculated, most commonly the coefficient of variation (CV). The CV standard selected for this pilot project was 30%. Assays with CVs >30% can repeat replicate testing or modify their assays to improve precision; the CAV can help with either of these possibilities, but assays will not advance to Cohort 1 without acceptable CV characteristics.

Bottom Line: In this model, the CAV facilitates the validation of candidate assay methods as well as qualification of proposed biomarkers for a specific clinical use in well-characterized patients.We describe here a CAV-driven pilot project aimed at identifying biomarkers that predict the rate of decline in beta cell function after diagnosis.This strategy could be a model for other collaborative biomarker development efforts in and beyond T1D.

View Article: PubMed Central - PubMed

Affiliation: Diabetes Clinical Research Program, Benaroya Research Institute, Seattle, WA, USA.

ABSTRACT
Recognizing an increasing need for biomarkers that predict clinical outcomes in type 1 diabetes (T1D), JDRF, a major funding organization for T1D research, recently instituted the Core for Assay Validation (CAV) to accelerate the translation of promising assays from discovery to clinical implementation via a process of coordinated evaluation of biomarkers. In this model, the CAV facilitates the validation of candidate assay methods as well as qualification of proposed biomarkers for a specific clinical use in well-characterized patients. We describe here a CAV-driven pilot project aimed at identifying biomarkers that predict the rate of decline in beta cell function after diagnosis. In a formalized pipeline, candidate assays are first assessed for general rationale, technical precision, and biological associations in a cross-sectional cohort. Those with the most favorable characteristics are then applied to placebo arm subjects of T1D intervention trials to assess their predictive correlation with beta cell function. We outline a go/no-go process for advancing candidate assays in a defined qualification pipeline that also allows for the discovery of novel predictive biomarker combinations. This strategy could be a model for other collaborative biomarker development efforts in and beyond T1D.

No MeSH data available.


Related in: MedlinePlus