Clinical Genomics Sub-team

• Sub-team is one of three that evolved out of the DIA Pharmacogenomics Standards Workshop.

• Workshop was product of collaborative effort between DIA, FDA, and several industry organizations (PWG, PhRMA, and BIO) and in follow-up to an earlier workshop (May 2002) that focused implication of PG and issues and application of these technologies in drug development and regulatory decision-making.

• Intent of this workshop was to provide forum for detailed review of the PDA proposal and draft guidance for PG Data Submissions. This guidance is intended to encourage voluntary submissions as well as submission of data in support of a regulatory decision-making.

Clinical Genomics Sub-team

• Broad sponsorship and involvement: HL7, CDISC, I3C, FDA

• Started with the use cases that were included in Backgrounder document from this meeting (put together to guide and stimulate discussion around FDA draft guidance document).

• Created a flow chart that based on a selected use case.

Compound XPhase IIb Efficacy

Study

Compound XPhase III Pivotal

Study

Peripheralblood

samples

Clinicaldata

Peripheral bloodmononuclear

cells before andafter treatment

Pharmogeneticanalyses: candidate

genes targeted basedon known metabolic

pathway

Gene ExpressionProfiling

SNPassociations to

safety andefficacy

paramters

Inclusioncriteria forPhase IIIpivotalstudy

Gene profilewith strongpredictive

accuracy forefficacy

Gene profilewith strongpredictive

accuracy forhypersenstivity

reaction

Submission toFDA

Peripheralblood

samples

Clinicaldata

Peripheral bloodmononuclear

cells before andafter treatment

Gene ExpressionProfiling

Reanalysis of alldata collected to

date

Product approval

Data frompharmagenetic

analysis conductedby other

researchers/companies: DNA

marker setprovisionally linked

with metabolicpathway for

Compound X

Treat Patients

Peripheralblood

samples

Clinicaldata

Pharmogeneticanalyses

EquivocalAssociation

Planning forCompound Y

Results ofreanalysisof genomic

data

Key Issues:

• Standards are important for pharmacogenomics submission data because – a) there is a large amount of data to handle; – b) it is necessary and desirable to compare across trials; and – c) need for consistency in review by various organizations

(biotechs, CROs, FDA).• In order to develop a recognizable standard in a short

timeframe, subteam has agreed we should not develop something totally new but rather adapt existing standards to our needs

• We need to increased our understanding of what the FDA wants to review. – Should we focus on the FDA required submissions or the

voluntary submissions? Is there a difference in scope?

Next steps

• Increase our understanding of what the FDA would like to see.

• Focus on one scenario (the microarray scenario).• Review and leverage work already done by SEND and

CDISC groups. FDA will likely want to integrate data from different sources through their viewing tools.

• Identify other existing standards that can be used.• Provide comments to FDA relevant to Draft Guidance• Harmonize with other relevant models