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Explore the generation of medical logic modules from electronic medical records for clinical trial eligibility criteria representation.
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Generating Medical Logic Modules forClinical 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 (especially pharmaceutical companies)
Clinical Trial Enrollment • Power in numbers • Traditional enrollment methods
What if . . . we could automatically extract eligibility criteria from electronic medical records?
Electronic Medical Records • 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 • Unstandardized realms
Thesis Statement • 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 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: . . .
MLM 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
MLM 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: . . . Logic Predicates Overview Trial
MLM 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: . . . Logic Predicates Overview Trial • Inclusion: • Gender: Female • Pregnant • Gestational age > 23.0 wks and < 31.6 wks • Exclusion: • Chorioamnionitis • Non-reassuring fetal testing
MLM 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: . . . Logic Predicates Overview Trial • (P1) Gender: Female • (P2) Pregnant • (P3) Gestational age > 23.0 wks • (P4) Gestational age < 31.6 wks • (P5) Chorioamnionitis • (P6) Non-reassuring fetal testing • Inclusion: • Gender: Female • Pregnant • Gestational age > 23.0 wks and < 31.6 wks • Exclusion: • Chorioamnionitis • Non-reassuring fetal testing
MLM 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: . . . Logic Predicates Overview Trial • (P1) Gender: Female • (P2) Pregnant • (P3) Gestational age > 23.0 wks • (P4) Gestational age < 31.6 wks • (P5) Chorioamnionitis • (P6) Non-reassuring fetal testing • Inclusion: • Gender: Female • Pregnant • Gestational age > 23.0 wks and < 31.6 wks • Exclusion: • Chorioamnionitis • Non-reassuring fetal testing P1 P2 (P3 P4) NOT (P5 P6) Or in conjunctive normal form: P1 P2 P3 P4 NOT P5 NOT P6
MLM 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: . . . Logic Predicates Overview Trial • (P1) Gender: Female • (P2) Pregnant • (P3) Gestational age > 23.0 wks • (P4) Gestational age < 31.6 wks • (P5) Chorioamnionitis • (P6) Non-reassuring fetal testing • Inclusion: • Gender: Female • Pregnant • Gestational age > 23.0 wks and < 31.6 wks • Exclusion: • Chorioamnionitis • Non-reassuring fetal testing P1 P2 (P3 P4) NOT (P5 P6) Or in conjunctive normal form: P1 P2 P3 P4 NOT P5 NOT P6
MLM 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: . . . Logic Logic Handling Predicates Term Mapping Overview Trial
MLM 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: . . . Logic Logic Handling Predicates Term Mapping Target Schema Other Knowledge UMLS Overview Trial
MLM 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: . . . Logic Logic Handling Predicates Term Mapping Target Schema Other Knowledge UMLS Overview Trial Additional Information
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 From vocabulary of target database pregnant: pregnancy pregnancy appointment type pregnant ambulatory status . . . has-parent: Diagnosis has-parent: Appointment type has-parent: Ambulatory status
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
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 Looking for “pregnancy” in schema of target database. PregnancyObservation : Is-Subtype-Of : DiagnosisAndFindingObservation { value(codedTerm({pregnancy, 83035})); negation(boolean); . . . }
Mapping Example 1 pregnant: pregnancy (83035) has-parent: diagnosis 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 : Is-Subtype-Of : DiagnosisAndFindingObservation { value(codedTerm({pregnancy, 83035})); negation(boolean); . . . } Look for “PregnancyObservation” in vocabulary of target database. PregnancyObservation (59665) has-parent: observation
Mapping Example 1 pregnant: pregnancy (83035) has-parent: diagnosis PregnancyObservation : Is-Subtype-Of : DiagnosisAndFindingObservation { value(codedTerm({pregnancy, 83035})); negation(boolean); . . . } PregnancyObservation (59665) has-parent: observation
Mapping Example 1 pregnant: pregnancy (83035) has-parent: diagnosis PregnancyObservation : Is-Subtype-Of : DiagnosisAndFindingObservation { value(codedTerm({pregnancy, 83035})); negation(boolean); . . . } PregnancyObservation (59665) has-parent: observation 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 Demographics Gender Female Male
Mapping Example 2 • Inclusion: • Gender: Female • Pregnant • Gestational age > 23.0 wks and < 31.6 wks • Exclusion: • Chorioamnionitis • Non-reassuring fetal testing Demographics Look in target database for a concept of ‘Gender’ with a value of ‘Female’. Gender Female Male
Unmappable Concepts • Concept or value not in target database • Concept does not exist “Delivery intended outside center” • Too Hard Inclusion: “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 Hard Inclusion: “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