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Generating Medical Logic Modules for Clinical Trial Eligibility

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 for Clinical Trial Eligibility

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  1. Generating Medical Logic Modules forClinical Trial Eligibility Craig Parker Brigham Young University

  2. 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)

  3. Clinical Trial Enrollment • Power in numbers • Traditional enrollment methods

  4. What if . . . we could automatically extract eligibility criteria from electronic medical records?

  5. 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

  6. 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

  7. 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

  8. 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: . . .

  9. Beginning . . .

  10. 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: . . .

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. Steps to Create MLMs • Classify predicates • Map concepts from trial to database • Translate logic • Generate MLM

  21. 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

  22. Mapping Example 1 • Inclusion: • Gender: Female • Pregnant • Gestational age > 23.0 wks and < 31.6 wks • Exclusion: • Chorioamnionitis • Non-reassuring fetal testing

  23. 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

  24. 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

  25. 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

  26. Mapping Example 1 pregnant: pregnancy (83035) has-parent: diagnosis

  27. Mapping Example 1 pregnant: pregnancy (83035) has-parent: diagnosis Looking for “pregnancy” in schema of target database.

  28. 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); . . . }

  29. 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.

  30. 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

  31. 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

  32. 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

  33. Mapping Example 2 • Inclusion: • Gender: Female • Pregnant • Gestational age > 23.0 wks and < 31.6 wks • Exclusion: • Chorioamnionitis • Non-reassuring fetal testing

  34. 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

  35. 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

  36. 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

  37. 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”

  38. 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

  39. 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

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