BIG DATA TO ACTIONABLE REPORTS

Don RuleJanuary 27, 2016

VisionTo inform every clinical decision affecting every patient everywhere in the world with the best available personalized guidance

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Human Cognitive Capacity

Source: Daniel R. Masys, M.D., University of Washington

Data

Data is Overwhelming Cognition

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What WorksGenetic test results are useless – understanding the implications quickly is priceless

Tailor reports to the audience – e.g. implications for the cardiologist, psychiatrist, or neurologist◦ Sometimes this means multiple focused reports for same patient

Avoid gratuitous graphics

Make sure it still works when you fax it

Alerts are always about the consequences, not the genetic result

Sometimes what was NOT tested is important

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Communicating What Matters

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X

Clinician’s Curiosity is Limited by TimeWhat we want to tell doctors

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What doctors have time to read

Consider alternatives to Codeine #CYP2D6RapidMetabolizer

Multi-Scalar Problem

Single SNP OPRM1 118A>G Opioid Efficacy

Multi-SNP MTHFR 1298C & 677T Hyperhomocysteinemia

Multi-GeneFactor II 20210A & Factor V Leiden 1691A

Thrombosis Risk

Multi-Allelers16947 + rs3892097 + rs1065852

CYP2D6 Haplotype

MixedCYP2C9 Phenotype & VKORC1 -1639G>A

Warfarin Sensitivity

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Easy to Misinterpret Complex Results

Communicating with Developers

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Case C0 C1 C2+ R117H 5T 7T 9T

CFTR01 TRUE

CFTR02 TRUE

CFTR03 TRUE

CFTR04 TRUE

CFTR05 TRUE TRUE

CFTR06 TRUE TRUE

CFTR07 TRUE TRUE

Validation in a Rapidly Evolving FieldINTERNET MODEL

Application

Presentation

Session

Transport

Network

Data Link

Physical

LABORATORY MODEL

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Report

KB Mashup

Phenotyping

Typing

Variant Calls

VCF

Assembly

You are Only as Good as Your KnowledgeMany gaps in the data◦ Variant databases are particularly gappy

Wide range in evidence quality

Real data is really messy

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ClinVar Stats

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Source: http://www.ncbi.nlm.nih.gov/clinvar/submitters/

135,430121,834

70,816

230

20,000

40,000

60,000

80,000

100,000

120,000

140,000

160,000

Unique variationrecords

Records withinterpretations

Records withassertion criteria

Records withpractice guidelines

A Note About Sequencing TestsLots of data

Perhaps not what you need◦ Difficult to infer structural Variation

◦ Exomes lacking regulatory regions

High costs & long turnaround time

Difficult validation

Non-Actionable data lowers the propensity to order tests

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Where we Need to Go

Reactive Preemptive

Static Dynamic

Just-in-Chart Portable

Standalone Integrated

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Implications of the New WorldGenetic testing is an integral part of the clinical workflow

Testing rational panels (yes, eventually genomes) not gene by gene

Decision support is what test to order as well as how to interpret results

Test may be ordered for one condition but data may be re-used for many other purposes

Data must be accessible to your GP as well as your cardiologist and dentist

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Evolution – Phase IGet basic data in EMR◦ PDF report – focused on the question at hand

◦ Alerts

◦ Best Practice Advisories

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Evolution - Phase IIClinical Decision Support extended to guide ordering

Institution-specific rules determine when a test is appropriate

Order set is compiled and sent through standard means

EMR Rules fire on receipt of test results to update the clinician

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Evolution – Phase IIIPhysician reviews report based upon alert

Physician – or pharmacist – queries the system to select an alternative medication

Result of medication review updates medication orders in the system

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ConclusionReporting is the primary product of a genetic test – should not be an afterthought

Human factors are as important as technical accuracy

Field is evolving rapidly – implications for quality control are profound

Our key mission is to service clinicians where they live

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Thank You!

Thanks from the Team!

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