ARUP Labs

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ARUP Labs the IRB

• Clinical Testing Research

April 2008
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What is ARUP Laboratories?

• National referral laboratory for esoteric testing
• Clients in all 50 states including more than half
  of the academic medical centers
• Clients are hospitals and labs, not physicians
• Offers over 2000 different tests
• Nearly 50 different laboratory sections
• Handles 30,000 samples per day
• Owned by the University of Utah
• Managed by the Department of Pathology

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Who Directs ARUP Laboratories?

• 50 medical directors direct laboratory sections
  or are involved with providing results
• All of these individuals are University of Utah
  faculty
• Most have a primary appointment in the Department
  of Pathology
• Pathology residents and clinical post-doctoral
  fellows in several disciplines train and perform
  research at ARUP Labs

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What is the Regulatory Environment?

• Clinical laboratories are regulated by CLIA 88
• CLIA dictates that laboratories validate the
  tests that they offer
• Validation may include
• Linearity
• Imprecision
• Method comparison
• Reference interval(s)
• Interferences
• Sensitivity and specificityanalytic and/or
  clinical
• ARUP is regularly inspected by the FDA, AABB,
  CAP, and New York Statevalidations are reviewed

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Assay Validations

• ARUP develops and validates
• 35 new assays each year
• 35 send out conversions each year
• Numerous assay improvements
• Mandated by CLIA, responsibility of medical
  directors
• May become research
• Published by university faculty and ARUP staff
• Publications are based on detailed assay
  validation or new assay development or related
  findings
• ARUP supports the publication of 110
  peer-reviewed manuscripts per year

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IRB Protocols

• 7275 De-identified body fluid samples for assay
  validation (exempt)
• 7740 Blood urine for assay validation (minimal
  risk, informed consent)
• 9200 Pediatric reference intervals 7-17 years
  (minimal risk, informed consent)
• 12291 Analysis of de-identified laboratory data
  (exempt)
• 15079 Pediatric reference intervals 6 mo-7 yrs
  (minimal risk, informed consent)
• 24431 Pathogen isolates from clinical samples
  (minimal risk)
• 24487 Formalin-fixed paraffin-embedded tissue for
  research (exempt)

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ARUP Labs the IRB

• Genetic Testing

April 2008
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Genetic Testing in Research

• Gene Discovery
• Genotype/Phenotype correlations
• Collect large pedigrees
• Clinic coordinator
• Interact directly with study participants
• Statistical Analysis
• Funded by grants

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Clinical Molecular Genetic Testing

• Validate test following ARUPs procedures
• De-identified
• Receive test requisition from physician or health
  care provider (HCP)
• Mutation analysis
• Provide report to ordering HCP
• Result
• Interpretation

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Results Interpretation

• Results
• No Mutations Detected
• Deleterious Mutation
• Benign Mutation
• Mutation with Uncertain Clinical Significance

• Uncertain
• Gather evidence for mutation classification
• Guidelines from ACMG
• Request additional sample for further workup (DNA
  vs RNA)
• Request family member
• Control
• Pedigree
• Findings specific for the patient

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Clinical Genetic Research

• Family correlation study
• Does the mutation track with disease in the
  family?
• Small pedigrees
• Statistical analysis
• Genotype/Phenotype correlation
• Several small families
• Public knowledge (databases, publications)
• De-identified issue of private mutation
• Contact physician to offer study to patient and
  family members
• Service to families
• Free of charge (ARUP covers costs)
• Generalize findings for others