Normalization of Phenotypic Data from a Clinical Data Warehouse: - - PowerPoint PPT Presentation

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Normalization of Phenotypic Data from a Clinical Data Warehouse: - - PowerPoint PPT Presentation

Feb 10, 2024 178 likes •484 views

Normalization of Phenotypic Data from a Clinical Data Warehouse: Case Study of Heterogeneous Blood Type Data with Surprising Results James J. Cimino, MD Formerly: Chief of the Laboratory for Informatics Development NIH Clinical Center,

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Normalization of Phenotypic Data from a Clinical Data Warehouse: Case Study of Heterogeneous Blood Type Data with Surprising Results James J. Cimino, MD Formerly: Chief of the Laboratory for Informatics Development NIH Clinical Center, National Institutes of Health Bethesda, Maryland, USA Now: Director, Informatics Institute University of Alabama at Birmingham Birmingham, Alabama, USA

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Lecture Overview

  • Started out trying to normalize laboratory data
  • Mapped different tests to common findings
  • Identified need to “atomize” data
  • Real data set found some surprises
  • Speculation on causes
  • Take-home messages
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Old EHR Personal System Lab System

BTRIS

Curent EHR

Biomedical Translational Research Information System (BTRIS)

Institute System

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ABO Blood Typing

  • from Wikipedia
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ABO and Rh Blood Typing

  • from Wikipedia

Rh Negative

  • Anti-

Rh Anti- Rh Anti- Rh Anti- Rh

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ABO and Rh Blood Typing

  • from Wikipedia

Rh Positive + + + +

R h R h R h R h R h R h R h R h

Rh antigen Rh antigen Rh antigen Rh antigen

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Panels Reporting Multiple Antigens and Interpretations

Panel Tests Result

ABO GRP-RH TYPE ABO GRP-RH TYPE O POSITIVE ABO GRP-RH TYPE ABO GRP-RH TYPE A POSITIVE ABO GRP-RH TYPE ABO GRP-RH TYPE A NEGATIVE ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - A ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - B 4+ ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - Rh POS ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - A ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - B ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - Rh NEG

B positive O negative

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What are the Underlying Atomic Findings?

  • from Wikipedia

Rh Positive + + + +

R h R h R h R h R h R h R h R h

Absence of A ag Absence of A ag Absence of B ag Absence of B ag Rh antigen Rh antigen Rh antigen Rh antigen

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Variants and Typographical Errors

Panel Tests Result

ABO GRP-RH TYPE ABO GRP-RH TYPE O POSITIVE ABO GRP-RH TYPE ABO GRP-RH TYPE 0 POS ABO GRP-RH TYPE ABO GRP-RH TYPE A POSITIVE ABO GRP-RH TYPE ABO GRP-RH TYPE A NEG ABO GRP-RH TYPE ABO GRP-RH TYPE A NEGATIVE ABO GRP-RH TYPE ABO GRP-RH TYPE AB NEG ABO GRP-RH TYPE ABO GRP-RH TYPE B POS ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - A ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - A 1+ ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - A 2+ ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - A 3+ ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - A 4+ ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - A M4 ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - B ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - B 4+ ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - Rh NEG ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - Rh POS

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Interpretation of Presence or Absence of Antigens

Panel Tests Result Antigens Summary

ABO GRP-RH TYPE ABO GRP-RH TYPE O POSITIVE abR ABO GRP-RH TYPE ABO GRP-RH TYPE 0 POS abR ABO GRP-RH TYPE ABO GRP-RH TYPE A POSITIVE AbR ABO GRP-RH TYPE ABO GRP-RH TYPE A NEG Abr ABO GRP-RH TYPE ABO GRP-RH TYPE A NEGATIVE Abr ABO GRP-RH TYPE ABO GRP-RH TYPE AB NEG ABr ABO GRP-RH TYPE ABO GRP-RH TYPE B POS aBR ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - A a

abR

ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - B 1+ b ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] – Rh Pos R ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - A 4+ A

ABr

ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - B 4+ B ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - Rh NEG r ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] – A a

abR

ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] – B b ABO Group and Rh Type [ABORH] ABO Group and Rh Type [ABORH] - Rh POS R

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Does the Atomic Approach Support Data Integration? Hypothesis: Different tests of the same blood type should produce the same atomic results. Experiment: Different tests on the same patient should produce the same atomic results.

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Experimenting with BTRIS

  • Queried BTRIS for all ABO and Rh test results
  • Identify unique panel/test combinations
  • Identify unique results of panel/tests combinations
  • Create atomic maps for each unique result
  • Identify each patient’s phenotype (union of atoms)
  • Examine phenotypes for discrepant results
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Summary of Results

43,760 Patients 176,676 Panels 593,637 Tests 23,903 patients with multiple panels 19,583 patients with single panel 479 discrepant phenotypes (2.00%) 66 unique Panels 139 unique Tests 334 unique Panel-Test combinations 3949 unique results Summarization 21 unique Panels 32 unique tests 59 unique Panel-Test combinations 1452 unique results Manual Review to Select Relevant Tests 43,486 patients 165,981 panels 307,884 Tests Filtering

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Expected Phenotypes

Antigenic Evidence Phenotype # Patients abR O+ 17132 AbR A+ 13925 aBR B+ 4710 abr O- 2538 Abr A- 2316 ABR AB+ 1441 aBr B- 645 ABr AB- 214

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Incomplete Phenotypes

Antigenic Evidence Phenotype # Patients r

  • 10

R + 8 ab O 7 Ab A 5 AB AB 1 aB B 1 bR + 1

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Discrepant Phenotypes

Antigenic Evidence Phenotype # Patients AabR (discrepant) 132 abRr (discrepant) 89 AbRr (discrepant) 67 aBbR (discrepant) 51 AaBbR (discrepant) 50 AabRr (discrepant) 28 ABbR (discrepant) 24 aBRr (discrepant) 19 AaBR (discrepant) 17 Aabr (discrepant) 13 aBbr (discrepant) 11 ABRr (discrepant) 7 AaBbRr (discrepant) 6 aBbRr (discrepant) 6 ABbr (discrepant) 6 AaBbr (discrepant) 3 ABbRr (discrepant) 2

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Examples of Same-Patient Discrepant Results

Subj Date Test Result Ags Interp. 59 1/31/1989 ABO & RH O POSIT. abR abR (O+) 59 1/31/1989 ABO & RH A POSIT. AbR AbR (O-) 724 1/24/1989 ABO & RH O NEG abr abr (O-) 724 2/13/1989 ABO & RH O POS abR abR (O+) 986 1/2/1999 ABO Group and Rh - Rh POS R ABR (AB+) 986 1/2/1999 ABO Group and Rh - A 4+ A 986 1/2/1999 ABO Group and Rh - B 4+ B 986 1/18/2000 ABO Group and Rh - Rh POS R AbR (A+) 986 1/18/2000 ABO Group and Rh - A 4+ A 986 1/18/2000 ABO Group and Rh – B b

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Examples of Same-Patient Discrepant Results

Subj Date Test Result Ags Interp. Phen. 59 1/31/1989 ABO & RH O POSIT. abR abR (O+) AabRr 59 1/31/1989 ABO & RH A POSIT. AbR AbR (O-) 724 1/24/1989 ABO & RH O NEG abr abr (O-) abRr 724 2/13/1989 ABO & RH O POS abR abR (O+) 986 1/2/1999 ABO Group and Rh - Rh POS R ABR (AB+) AbBR 986 1/2/1999 ABO Group and Rh - A 4+ A 986 1/2/1999 ABO Group and Rh - B 4+ B 986 1/18/2000 ABO Group and Rh - Rh POS R AbR (A+) 986 1/18/2000 ABO Group and Rh - A 4+ A 986 1/18/2000 ABO Group and Rh – B b

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More Examples of Same-Patient Discrepant Results

Subj Date Test Result Ags Interp. 1090 1/2/2002 ABO Group and Rh - ABO A Ab AbR (A+) 1090 1/2/2002 ABO Group and Rh - Rh POS R 1090 1/2/2002 ABO Group and Rh - A 4+ A 1090 1/2/2002 ABO Group and Rh - B b 1090 1/28/2003 ABO Group and Rh - ABO B aB aBR (B+) 1090 1/28/2003 ABO Group and Rh - Rh POS R 1090 1/28/2003 ABO Group and Rh - A a 1090 1/28/2003 ABO Group and Rh - B 4+ B

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More Examples of Same-Patient Discrepant Results

Subj Date Test Result Ags Interp. Phen. 1090 1/2/2002 ABO Group and Rh - ABO A Ab AbR (A+) AaBbR 1090 1/2/2002 ABO Group and Rh - Rh POS R 1090 1/2/2002 ABO Group and Rh - A 4+ A 1090 1/2/2002 ABO Group and Rh - B b 1090 1/28/2003 ABO Group and Rh - ABO B aB aBR (B+) 1090 1/28/2003 ABO Group and Rh - Rh POS R 1090 1/28/2003 ABO Group and Rh - A a 1090 1/28/2003 ABO Group and Rh - B 4+ B

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Possible Explanation: Random Laboratory Error

  • Doubling the tests for a patient should double

the chance of random error

  • bCorrelation was 0.7127 (P<.00001) but slope

was only 0.04 (not 0.5)

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7 discrepant phenotypes (0.04%) 43,760 Patients 176,676 Panels 593,637 Tests 23,903 patients with multiple panels 19,583 patients with single panel 479 discrepant phenotypes (2.00%) 66 unique Panels 334 unique Panel-Test combinations 139 unique Tests 3949 unique results Summarization 21 unique Panels 59 unique Panel-Test combinations 32 unique tests 1452 unique results Manual Review to Select Relevant Tests 43,486 patients 165,981 panels 307,884 Tests Filtering

Summary of Results: Discrepancies within a single panel

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Examples of Discrepant Results within Single Panel

Subj Date Test Result Ags Interp. 2185 1/11/199 1 ABO & RH O NEG abr abRr (O+/O-) 2185 1/11/199 1 ABO & RH O POS abR 3986 1/18/200 ABO Group and Rh - ABO AB AB ABbR (AB+/A+) 3986 1/18/200 ABO Group and Rh - Rh POS R 3986 1/18/200 ABO Group and Rh - A 4+ A 3986 1/18/200 ABO Group and Rh - B B

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Examples of Discrepant Results within Single Panel

Subj Date Test Result Ags Interp. Phen. 2185 1/11/199 1 ABO & RH O NEG abr abRr (O+/O-) abRr 2185 1/11/199 1 ABO & RH O POS abR 3986 1/18/200 ABO Group and Rh - ABO AB AB ABbR (AB+/A+) ABbR 3986 1/18/200 ABO Group and Rh - Rh POS R 3986 1/18/200 ABO Group and Rh - A 4+ A 3986 1/18/200 ABO Group and Rh - B B

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Possible Explanations

  • Laboratory error
  • Rare changes from:

Leukemia Transplantation Viral infections

  • Manual record review necessary
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Other Applications of Atomic Representation Approach

  • Antibiotic resistance

 Culture: S. aureus + Methicillin sensitivity: R  Culture: Methicillin-resistant S. aureus  Methicillin-resistant S. aureus test: “Positive”

  • Microbiology antibodies and antigens
  • Anatomic descriptions

 Diagnosis: “Left upper lobe pneumonia”  Diagnosis: “Pneumonia” + Location: “Left upper lobe”

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Take-Home Messages

1.

Merging data from multiple EHRs requires a unified method for interpretation

2.

Breaking down findings into atomic components is a viable approach for some situations

3.

Analysis of real-world data may show that basic assumptions must be questioned  In theory: Theory = Practice  In practice: Theory ≠ Practice

Acknowledgements: This work was supported by intramural research funds from the NIH Clinical Center and the National Library

  • f Medicine.