From the Bench All the Way to Bedside Clinical Decision Support:

The Role of Semantic Technologies in a Knowledge Management Infrastructure for Translational Medicine

Tonya Hongsermeier, MD, MBACorporate Manager, Clinical Knowledge Management and Decision

Support

Clinical Informatics R&DPartners Healthcare System

Current State of Translational Medicine• 17 year innovation adoption curve from

discovery into accepted standards of practice

• Even if a standard is accepted, patients have a 50:50 chance of receiving appropriate care, a 5-10% probability of incurring a preventable, anticipatable adverse event

• The market is balking at healthcare inflation, new diagnostics and therapeutics will find increasing resistance for reimbursement

The Volume and Velocity of Knowledge Processing Required for Care Delivery

• Medical literature doubling every 19 years— Doubles every 22 months for AIDS care

• 2 Million facts needed to practice • Genomics, Personalized Medicine will increase

the problem exponentially• Typical drug order today with decision support

accounts for, at best, Age, Weight, Height, Labs, Other Active Meds, Allergies, Diagnoses

• Today, there are 3000+ molecular diagnostic tests on the market, typical HIT systems cannot support complex, multi-hierarchical chaining clinical decision support

Covell DG, Uman GC, Manning PR. Ann Intern Med. 1985 Oct;103(4):596-9

Today’s Health IS VendorKnowledge Management Capabilities:• Knowledge “hardwired” or structured in proprietary

modes into applications, not easily updated or shared• Little or no standardization of HIT vendors on SNOMED,

no shared interface terminologies for observation capture, no standard order catalogues

• Most EMRs have a task-interfering approach to decision support, sub-optimal usability

• Knowledge-engineering tools typically edit into transaction, no support for provenance, versioning, life-cycle, propagation, discovery or maintenance

• Consequently, clinical systems implementations are under-resourced with adequate knowledge to meet current workflow and quality needs

• Labor of converting knowledge into Clinical Decision Support is vastly underestimated

• Doesn’t bode well for personalized medicine

Knowledge Management and Decision Support Intersection Points in Translational Medicine

Patient Encounter(direct care or clinical trial)

Diagnostic Test orderingand documentation

guidance

Therapeutic InterventionOrdering and documentation

guidance

Integrated GenotypicPhenotypic Databases

Personalized MedicineDecision Support

Knowledge Repository Tissue-bank

ClinicalTrials Referral

KnowledgeDiscovery,

Acquisition &Management

Structured ResearchAnnotations

Bench R&D

Clinical Trials 1- 4

Pharmacovigilance

Structured TestResult Interpretations

Composite Decision Support Application: Diabetes Management

Guided Data Interpretation Guided Observation Capture Guided Ordering

What healthcare needs from Semantic Web Technologies…• Reduce the cost, duration, risk of drug discovery

• Data integration, Knowledge integration, Visualization• Knowledge representation New Knowledge Discovery

• Reduce the cost/duration/risk of clinical trial management• Patient identification and referral• Trial design (ie to capture better safety surveillance)• Data quality and clinical outcomes measurement• Post-market surveillance

• Reduce the cost/duration/liability of knowledge acquisition and maintenance for clinical decision support and clinical performance measurement

• Knowledge provenance and representation• Conversion of “discovery algorithms” into “clinical practice

algorithms”• Event-driven change management and propagation of change

KM for Translational Medicine: Functional/Business Architecture

PORTALSR&D CLINICAL TRIALSDIAGNOSTIC Svs LABs CLINICAL CARE

LIMS EHR

ASSAYSANNOTATIONS

DIAGNOSTIC TEST RESULTSASSAY INTERPRETATIONS

ORDERS AND OBSERVATIONS

Genotypic Phenotypic

Data Domains

Knowledge Domains

Logic/Policy Domains

DATA REPOSITORIES AND SERVICES

KNOWLEDGE ACQUISITIONAND DISCOVERY SERVICES

NCI Metathesaurus, UMLS,SNOMED CT, DxPlain, ETC other Knowledge Sources

Data Analysts andCollaborative Knowledge

Engineers

Semantic InferencingAnd Agent-based

Discovery Services

KNOWLEDGE and WORKFLOW DELIVERY SERVICES FOR ALL PORTAL ROLES

DecisionSupport Services

Knowledge Asset Management and Repository Services

CollaborationSupport Services

WorkflowSupport Services

State Management

Services

APPLICATIONS

Meta-Knowledge

INFERENCING AND VOCABULARY ENGINES

Example: Diabetes

• Epidemic, associated with obesity• Quality measures drive reimbursement of

hospitals and physicians• Maintain HbA1c <7 (diet, oral agents and/or insulin)• If Renal Disease and no contraindication, should be

on ACE inhibitor or ARB• If lipid disorder and no contraindication, should be on

a Statin

• National problem of non-compliance with these standards of care compromised patient longevity, quality of life, ability to maintain employment CMS and employer financial risk

• Renal disease =—Chronic Renal Failure

• Nephropathy, chronic renal failure, end-stage renal disease, renal insufficiency, hemodialysis, peritoneal dialysis on Problem List (SNOMED)

• Creatinine > 2• Calculated GFR < 50

—Malb/creat ratio test > 30• Diabetes

• Many variants on the problem list• On Insulin or oral hypoglycemic drug

• Contraindication to ACE inhibitor• Allergy, Cough on ACE on adverse reaction list, or

Hyperkalemia on problem list, Pregnant (20 sub rules to define this state)

• K test result > 5

Imagine this CDS Rule:If Renal Disease and DM and no contraindication, should be on ACE inhibitor or ARB

Composite Decision Support Application: Diabetes Management

Guided Data Interpretation Guided Observation Capture Guided Ordering

The Maintenance and Propagation Challenge…

• These “complex” definitions must be identical in rules (if that is how “recognition” is handled), documentation templates for structured data capture, and in reporting systems that drive payor reimbursement

• The rate of change for contraindication definition today is slow, yet clinical decision support systems are not keeping up…

• When molecular diagnostics take off, this rate of change could be “daily” or “hourly”

• Further, when a patient has a molecular diagnostic test result in the EMR that is currently of “unknown significance” and later, with new knowledge, the interpretation of the former result is “contraindication” to a drug, then this “interpretation” must be updated to ensure proper CDS functioning…

Role of Semantic Technologies…• Data/Knowledge Integration and Visualization

• Ontology based approaches• Integration across multiple data sources:

• Genotypic/Phenotypic data from LIMS/HER• Knowledge Repositories for data interpretation

• Clinical Decision Support• Inference engines - SWRL• Description logics for “recognition” - OWL• Knowledge representation • Etc.

• Knowledge Acquisition, Maintenance and Evolution• Ontology-based Definitions Management• Versioning, life-cycle, propagation into “dependent” objects such as

rules, templates orders/documentation, reporting systems• Knowledge Provenance• Reconciling knowledge representation among different stakeholders

(care givers, payors, performance measurement, clinical trials, R&D)

Market Drivers Will Make Semantic Web Technologies an Imperative for Translational Medicine

• Genomics: personalized medicine will require decision support architectures that can proactively support complex decision making – answering 1,000,000 of questions before run-time

• These systems will require self-adaptive, machine learning modes of knowledge acquisition, purely human dependent knowledge acquisition will not scale

• Pharma will need cooperative relationships with HIT vendors to make speed the translational medicine life-cycle