Generating Medical Logic Modules for Clinical Trial Eligibility

Generating Medical Logic Modules for

Clinical Trial Eligibility

Craig Parker

Brigham Young University

Clinical Trials

Important for modern medical research Efficacy of therapies Safety of therapies

Sponsored by Government (www.clinicaltrials.gov) Academic institutions Industry (e.g. pharmaceutical companies)

Clinical Trial Enrollment

Power in numbers Traditional enrollment methods have limitations

Methods Limitations

Regular office visits Limited pool of patients

Advertising Limited medical knowledge,

Cost

Chart review Limited information,

Requires medical training

What if . . .

we could automatically extract eligibility criteria from electronic medical records?

Electronic Medical Records (EMRs)

Good News Large amounts of data being collected Efforts to standardize representations are well

supported Bad News

Most EMRs are far from complete Not all representations are in a standard form

Legacy data / Legacy data acquisition tools Unstandardized realms

Automating the Process

Generate medical logic modules to represent eligibility criteria for clinical trials Start with criteria as first-order predicate logic Map concepts with medical vocabularies and

ontologies Create medical logic modules Handle concepts that can’t be mapped

Measure results

Medical Logic Modules (MLMs)

An abstract term describing the knowledge necessary for making a medical decision

A specific type of medical program Represented using the Arden Syntax

ANSI standard Broad vendor acceptance Compiles to an executable form

MLM in Arden Syntax

KNOWLEDGE: TYPE: . . . DATA: gestational_age := read last {SELECT gest_age FROM Observation}; ;;

EVOKE: . . . LOGIC: IF gestational_age >= 73 days AND gestational_age <= 97 days THEN conclude true; ENDIF; ;; ACTION: . . .

Beginning . . .

Beginning and End

KNOWLEDGE: TYPE: . . . DATA: gestational_age := read last {SELECT gest_age FROM Observation}; ;;

EVOKE: . . . LOGIC: IF gestational_age >= 73 days AND gestational_age <= 97 days THEN conclude true; ENDIF; ;; ACTION: . . .

Overview

Trial KNOWLEDGE: TYPE: . . . DATA: gestational_age := read last {SELECT gest_age FROM Observation}; ;;

EVOKE: . . . LOGIC: IF gestational_age >= 73 days AND gestational_age <= 97 days THEN conclude true; ENDIF; ;; ACTION: . . .

MLM

Overview

TrialPredicates

Expression

KNOWLEDGE: TYPE: . . . DATA: gestational_age := read last {SELECT gest_age FROM Observation}; ;;

EVOKE: . . . LOGIC: IF gestational_age >= 73 days AND gestational_age <= 97 days THEN conclude true; ENDIF; ;; ACTION: . . .

MLM

Overview

TrialPredicates

Expression

KNOWLEDGE: TYPE: . . . DATA: gestational_age := read last {SELECT gest_age FROM Observation}; ;;

EVOKE: . . . LOGIC: IF gestational_age >= 73 days AND gestational_age <= 97 days THEN conclude true; ENDIF; ;; ACTION: . . .

MLM

Inclusion: Gender: Female Pregnant Gestational age > 23.0 wks and

< 31.6 wks Exclusion:

Chorioamnionitis Non-reassuring fetal testing

Overview

TrialPredicates

Expression

KNOWLEDGE: TYPE: . . . DATA: gestational_age := read last {SELECT gest_age FROM Observation}; ;;

EVOKE: . . . LOGIC: IF gestational_age >= 73 days AND gestational_age <= 97 days THEN conclude true; ENDIF; ;; ACTION: . . .

MLM

Inclusion: Gender: Female Pregnant Gestational age > 23.0 wks and

< 31.6 wks Exclusion:

Chorioamnionitis Non-reassuring fetal testing

(P1) Gender: Female (P2) Pregnant (P3) Gestational age > 23.0 wks (P4) Gestational age < 31.6 wks (P5) Chorioamnionitis (P6) Non-reassuring fetal testing

Overview

TrialPredicates

Expression

KNOWLEDGE: TYPE: . . . DATA: gestational_age := read last {SELECT gest_age FROM Observation}; ;;

EVOKE: . . . LOGIC: IF gestational_age >= 73 days AND gestational_age <= 97 days THEN conclude true; ENDIF; ;; ACTION: . . .

MLM

Inclusion: Gender: Female Pregnant Gestational age > 23.0 wks and

< 31.6 wks Exclusion:

Chorioamnionitis Non-reassuring fetal testing

(P1) Gender: Female (P2) Pregnant (P3) Gestational age > 23.0 wks (P4) Gestational age < 31.6 wks (P5) Chorioamnionitis (P6) Non-reassuring fetal testing

P1 P2 (P3 P4) (P5 P6)

Or in conjunctive normal form:

P1 P2 P3 P4 P5 P6

Overview

TrialPredicates

Expression

KNOWLEDGE: TYPE: . . . DATA: gestational_age := read last {SELECT gest_age FROM Observation}; ;;

EVOKE: . . . LOGIC: IF gestational_age >= 73 days AND gestational_age <= 97 days THEN conclude true; ENDIF; ;; ACTION: . . .

MLM

Inclusion: Gender: Female Pregnant Gestational age > 23.0 wks and

< 31.6 wks Exclusion:

Chorioamnionitis Non-reassuring fetal testing

(P1) Gender: Female (P2) Pregnant (P3) Gestational age > 23.0 wks (P4) Gestational age < 31.6 wks (P5) Chorioamnionitis (P6) Non-reassuring fetal testing

P1 P2 (P3 P4) (P5 P6)

Or in conjunctive normal form:

P1 P2 P3 P4 P5 P6

Overview

Trial

TermMapping

LogicHandling

Predicates

Expression

KNOWLEDGE: TYPE: . . . DATA: gestational_age := read last {SELECT gest_age FROM Observation}; ;;

EVOKE: . . . LOGIC: IF gestational_age >= 73 days AND gestational_age <= 97 days THEN conclude true; ENDIF; ;; ACTION: . . .

MLM

Overview

Trial

TermMapping

LogicHandling

Predicates

Expression

UMLSOther

Knowledge

Target Schema

KNOWLEDGE: TYPE: . . . DATA: gestational_age := read last {SELECT gest_age FROM Observation}; ;;

EVOKE: . . . LOGIC: IF gestational_age >= 73 days AND gestational_age <= 97 days THEN conclude true; ENDIF; ;; ACTION: . . .

MLM

Overview

Trial

AdditionalInformation

TermMapping

LogicHandling

Predicates

Expression

UMLSOther

Knowledge

Target Schema

KNOWLEDGE: TYPE: . . . DATA: gestational_age := read last {SELECT gest_age FROM Observation}; ;;

EVOKE: . . . LOGIC: IF gestational_age >= 73 days AND gestational_age <= 97 days THEN conclude true; ENDIF; ;; ACTION: . . .

MLM

Steps to Create MLMs

Classify predicates Map concepts from trial to database Translate logic Generate MLM

Classifying Predicates

Numeric comparisons e.g. gestational age > 23.0 wks time, lab values, physiologic measurements

Single noun phrases e.g. pregnant diagnoses, observations

Two noun phrases e.g. Gender: Female name-value pairs

Mapping Example 1 Inclusion:

Gender: Female Pregnant Gestational age > 23.0 wks and

< 31.6 wks Exclusion:

Chorioamnionitis Non-reassuring fetal testing

Mapping Example 1 Inclusion:

Gender: Female Pregnant Gestational age > 23.0 wks and

< 31.6 wks Exclusion:

Chorioamnionitis Non-reassuring fetal testing

Single noun phrase – likely to be a diagnosis or

observation

Mapping Example 1 Inclusion:

Gender: Female Pregnant Gestational age > 23.0 wks and

< 31.6 wks Exclusion:

Chorioamnionitis Non-reassuring fetal testing

pregnant:

pregnancy

pregnancy appointment type

pregnant ambulatory status

. . .

has-parent: Diagnosis

has-parent: Appointment type

has-parent: Ambulatory status

From vocabulary of target database

Mapping Example 1 Inclusion:

Gender: Female Pregnant Gestational age > 23.0 wks and

< 31.6 wks Exclusion:

Chorioamnionitis Non-reassuring fetal testing

pregnant:

pregnancy

pregnancy appointment type

pregnant ambulatory status

. . .

has-parent: Diagnosis

has-parent: Appointment type

has-parent: Ambulatory status

Mapping Example 1

pregnant:

pregnancy (83035) has-parent: diagnosis

Looking for “pregnancy” in schema of target database.

Mapping Example 1

pregnant:

pregnancy (83035) has-parent: diagnosis

PregnancyObservation : Is-Subtype-Of : DiagnosisAndFindingObservation {

value(codedTerm({pregnancy, 83035}));negation(boolean);. . .

}

Looking for “pregnancy” in schema of target database.

Mapping Example 1

pregnant:

pregnancy (83035) has-parent: diagnosis

Look for “PregnancyObservation” in vocabulary of target database.

PregnancyObservation : Is-Subtype-Of : DiagnosisAndFindingObservation {

value(codedTerm({pregnancy, 83035}));negation(boolean);. . .

}

Mapping Example 1

pregnant:

pregnancy (83035) has-parent: diagnosis

PregnancyObservation (59665) has-parent: observation

PregnancyObservation : Is-Subtype-Of : DiagnosisAndFindingObservation {

value(codedTerm({pregnancy, 83035}));negation(boolean);. . .

}

Look for “PregnancyObservation” in vocabulary of target database.

Mapping Example 1

pregnant:

pregnancy (83035) has-parent: diagnosis

PregnancyObservation (59665) has-parent: observation

PregnancyObservation : Is-Subtype-Of : DiagnosisAndFindingObservation {

value(codedTerm({pregnancy, 83035}));negation(boolean);. . .

}

SELECT * FROM Observations WHERE ObsId = 59665 AND value = 83035

Mapping Example 2 Inclusion:

Gender: Female Pregnant Gestational age > 23.0 wks and

< 31.6 wks Exclusion:

Chorioamnionitis Non-reassuring fetal testing

Mapping Example 2 Inclusion:

Gender: Female Pregnant Gestational age > 23.0 wks and

< 31.6 wks Exclusion:

Chorioamnionitis Non-reassuring fetal testing

Two noun phrases – likely to be a name-

value pair

Mapping Example 2 Inclusion:

Gender: Female Pregnant Gestational age > 23.0 wks and

< 31.6 wks Exclusion:

Chorioamnionitis Non-reassuring fetal testing

Gender

MaleFemale

Demographics

Look in target database for a concept of ‘Gender’ with a value of ‘Female’.

Unmappable Concepts

Concept or value not in target database Concept does not exist

“Delivery intended outside center”

Too HardInclusion: “Received full course of corticosteroids in the previous 7 days”Exclusion: “Corticosteroid therapy, other than qualifying course”

Unmappable Concepts

Concept or value not in target database Concept does not exist

“Delivery intended outside center”

Too HardInclusion: “Received full course of corticosteroids in the previous 7 days”Exclusion: “Corticosteroid therapy, other than qualifying course”

Solution Evaluate eligibility based on available data If eligibility is possible, present questionnaire to user

for outstanding information needed

Evaluation

Select ~25 trials (~200 predicates) from ClinicalTrials.gov

Precision and recall of term mappings Precision and recall of predicate mappings Percentage of predicates that are mappable Correctness of logic in Arden Syntax modules