FDA (CDER) project billed as:

• Standardizing key study data specific to therapeutic areas (TAs)
• facilitate clinical research and the evaluation of medical products
• prioritized by:
  • particular medical need
  • existing data standardization projects
  • greater drug development pipeline activity
• each scoped to be done in 1 year
• "subsequent projects in those areas build on the results"
• all due December 2017

• across studies.
• across TAs.
• evolvable.

Metadata

• Share concepts between submissions.
• Eliminate ambiguities and synonyms.
• Enable search for studies.

Data (standards all the way down)

1. Define model and format.
2. Normalize terminology.
3. Data unification/integration.

SELECT ?outcomeType ?dose
       (AVG(?endpoint-time) AS ?rate)
 WHERE {
    # drug of interest
    ?adminDrug dt:CD.displayName "Upsidasium" ;
        … codingSystem … .

    # subjects in studies about drug
    ?arm :studySubject ?adminDrug ;
        :studyParticipation ?subject .

    # demographic selection
    ?subject :taxon ncbitax:9606 .

    # outcomes assessing prescription performance
    ?outcome :intervention ?p ;
        :value [ a ?outcomeType ] .

    # ... of that drug on that subject (participation)
    ?p a :Prescription ;
        :involvedSubject ?subject ;
        :medication ?adminDrug .
} ORDER BY ?dose

code everything

minimize:

• ambiguity - one way to write two things.
• diffusion - two ways to write one thing.

cope gracefully with:

• diversity - huge range of assertions.
• stratification - assertions in intersection of multiple terminologies.

interoperate with EHRS:

• FHIR
• OpenEHR
• C-CDA
• Vista
• vendors: EPIC, Cerner, Siemens, ...

RDF toolbox available for reuse

Existing Models/Standards

• BRIDG
• SDTM
• ODM
• SDM
• HL7 RIM
• CDASH
• etc.

Controlled Terminologies:

• MedDRA
• LOINC
• SNOMED
• etc.

Therapeutic Efficacy is comprised of:

• Interventions
  • Drugs
  • Procedures
  • Behavioral Modifications
• Observations
  • Clinical, Administrative (e.g. Disposition)
  • Single Observations
  • Assessments (“roll-ups” of single observations)
    • Outcomes (pre- and post-intervention assessments)
    • Therapeutic Efficacy Points (“roll-ups” of outcomes)
• Physiologic/Pathophysiologic Processes
  • Physiologic/Pathophysiologic Processes

How is clinical data submitted today?

• SDTM
• ODM
• SDM
• CDASH
• Atom

All lean on lists of study/domain-specific terms.

Issues:

• Abuse of core terms -- e.g. prescription vs. administration.
• Extension identifiers re-used for different purposes.
• What's an extension today can become core tomorrow.

• Use BRIDG where possible.
  • Collective effort of CDISC, HL7, NCI and FDA
  • Represents clinical trial planning, specialization, scheduling and execution.
  • Available in OWL
• Specialize bridg:PerformedObservation
  • PerformedObservation - all RenalTransplantation studies share a notion of a Serum Creatine test.
• Represent some protocol and stats
• factor factor factor…

Portable BRIDG Representation

• RenalTransplant is tiny
• trivial interop with:
  • ComplicatedUTI - renal functions
  • RheumatoidArthritis - Immunosuppression
  • all - bridg:MedicationAdminstration

Make clinical observations queriable:

• across studies.
• across TAs.

  ?arm :studySubject ?adminDrug

• evolvable.

SELECT ?outcomeType ?dose
       (AVG(?endpoint-time) AS ?rate)
 WHERE {
    # drug of interest
    ?adminDrug dt:CD.displayName "Upsidasium" ;
        … codingSystem … .

    # subjects in studies about drug
    ?arm :studySubject ?adminDrug ;
        :studyParticipation ?subject .

    # demographic selection
    ?subject :taxon ncbitax:7609 .

    # outcomes assessing prescription performance
    ?outcome :intervention ?p ;
        :value [ a ?outcomeType ] .

    # ... of that drug on that subject (participation)
    ?p a :Prescription ;
        :involvedSubject ?subject ;
        :medication ?adminDrug .
} ORDER BY ?dose