1. Clinical Research Informatics: From Bedside to Silicon and Back
Laura K. Wiley
Division of Biomedical Informatics and Personalized Medicine
Dept of Biostatistics and Informatics
@GenomeGal

2. So what is Clinical Research Informatics?

3. What’s in an EHR?

4. How can we leverage EHRs?
Clinical Trial Recruitment
Analytics/ Learning Healthcare System
EHR Repository
Population Health/ Epidemiology
Link to Biobank for Genetic Research

5. Coming Soon to a University Near You!

6. I’m doing a study on diabetes…
Compass can you get me a list of all the diabetics?

7. How Do We Find Phenotypes?
Natural Language Processing/
Keywords
Billing codes
True cases
Laboratory Measurements
Medications

8. How Do We Find Phenotypes?
Definite Cases (algorithm-defined)
Possible Cases (require manual review)
Excluded (algorithm-defined)
Controls (algorithm-defined)

9. A More Complex Example – Drug Adverse Reactions
Statins –
Widely used
~1/4 Americans > 45 circa 2010
Myotoxicity side-effect leading cause of discontinuation

10. Goal
Test a variety of phenotyping algorithms against a single, consistent definition of statin myotoxicity.
“Any muscle symptom attributed to statin by care provider anywhere in the patient’s medical record.”
Wiley, et. al. AMIA Jt Summits Transl Sci Proc. 2015

11. Methods – ICD9 & CK Algorithms
ICD-9 Codes Alone
Drug Side Effect (5, e.g., – poisoning by antilipemic & antiarteriosclerotic drugs)
General Muscle Effects (7, e.g., – myopathy unspecified)
Creatine Kinase (CK) – after 1st Statin
CK > 3x Upper Limit Normal (ULN)
CK (any value), not at same time as troponin
CK > 3x ULN, not at same time as troponin
CK (any value), only measurement in 5 days
CK > 3x ULN, only measurement in 5 days
Wiley, et. al. AMIA Jt Summits Transl Sci Proc. 2015

12. Methods – Allergy Algorithms
Listed Drug Allergies
Problem List
HISTORY OF PRESENT ILLNESS: Mr. XXX is a pleasant 50 year old gentleman with a history of diabetes mellitus and hyperlipidemia who presents with unspecified muscle pains, possibly due to his statin.
ALLERGIES: Statins unkown; Atorvastatin causes myopathy
MEDICATIONS: Metformin, Niacin, Pitavastatin
History & Physical
Adverse & Allergic Drug Reactions
Atorvastatin (unknown)
Simvastatin (LFTs)
Medications
Metformin ER 500 mg
Pitavastatin 4mg
Niacin 250mg
Health Problems
Diabetes Mellitus
Hyperlipidemia
All Code Available at:
Wiley, et. al. AMIA Jt Summits Transl Sci Proc. 2015

13. Methods – Keyword Algorithms
Keyword Searching
Clinical Comm.
History & Physical
**NAME[STARUSER]: Mr. XXX called saying that he is having severe muscle pain after increasing his dose of atorvastatin and would to know what to do.
**NAME[STARUSER]: Please call him back and tell his to stop taking the statin for 2 wks and see if his symptoms resolve.
**NAME[STARUSER]: Done.
**NAME[STARUSER]: Mr. XXX called saying that he is having severe muscle pain after increasing his dose of atorvastatin and would to know what to do.
**NAME[STARUSER]: Please call him back and tell his to stop taking the statin for 2 wks and see if his symptoms resolve.
**NAME[STARUSER]: Done.
**NAME[STARUSER]: Mr. XXX called saying that he is having severe muscle pain after increasing his dose of atorvastatin and would to know what to do.
**NAME[STARUSER]: Please call him back and tell his to stop taking the statin for 2 wks and see if his symptoms resolve.
**NAME[STARUSER]: Done.
HISTORY OF PRESENT ILLNESS: Mr. XXX is a pleasant 50 year old gentleman with a history of diabetes mellitus and hyperlipidemia who presents with unspecified muscle pains, possibly due to his statin.
ALLERGIES: Statins unkown; Atorvastatin causes myopathy
MEDICATIONS: Metformin, Niacin, Pitavastatin
HISTORY OF PRESENT ILLNESS: Mr. XXX is a pleasant 50 year old gentleman with a history of diabetes mellitus and hyperlipidemia who presents with unspecified muscle pains, possibly due to his statin.
ALLERGIES: Statins unkown; Atorvastatin causes myopathy
MEDICATIONS: Metformin, Niacin, Pitavastatin
HISTORY OF PRESENT ILLNESS: Mr. XXX is a pleasant 50 year old gentleman with a history of diabetes mellitus and hyperlipidemia who presents with unspecified muscle pains, possibly due to his statin.
ALLERGIES: Statins unkown; Atorvastatin causes myopathy
MEDICATIONS: Metformin, Niacin, Pitavastatin
2.64, 5.33
0.5, 2.64
All Code Available at:
Wiley, et. al. AMIA Jt Summits Transl Sci Proc. 2015

14. Results – Algorithms Performance
ICD-9 Codes
CK Elevation
Allergies
Keywords
Combined
Allergy+Keyword
Allergy+Keyword+ ICD-9
Allergy+Keyword+ ICD-9 + CK (any value) no troponin
ICD-9 (PPV/Precision ~ 0.7; NPV ~0.7)
Sensitivity/Recall: 0.48
Specificity: 0.86
PPV = 0.7
NPV = 0.7
Creatine Kinase (PPV ~ ; NPV ~ )
CK >500, single measurement
Sensitivity: 0.07
Specificity: 0.97
CK (any), single measurement; CK>500, any or no troponin
Sensitivity:
Specificity:
CK (any) no troponin
Sensitivity: 0.89
Specificity: 0.35
Allergy – Combined (PPV ~88->97%; NPV ~79%)
Sensitivity: > 0.63
Specificity: > 0.99
Keyword – Combined (PPV ~78-85%; NPV ~85->87%)
Sensitivity: > 0.81
Specificity: > 0.90
Combined Text Only (PPV ~ 86%; identified 109 of the 123 cases)
Sensitivity: 0.88
Specificity: 0.90
Combined Text & ICD9 (PPV ~ 81%; identified 116 of the 123 cases)
Sensitivity: 0.94
Specificity: 0.84
Combined All (PPV ~ 51%; identified 122 of the 123 cases)
Sensitivity: 0.99
Specificity: 0.32
Wiley, et. al. AMIA Jt Summits Transl Sci Proc. 2015

15. What’s Your Application?
Clinical Trial Recruitment
Analytics/ Learning Healthcare System
EHR Repository
Population Health/ Epidemiology
Link to Biobank for Genetic Research

16. Some General thoughts….
Detected truth
Who the algorithm detects as having a rxn
Case/Control
Algorithm Approach
& Implementation
Recorded Truth
If / How medical record contains reaction
Manual Review
Patient – Provider Conversation
Absolute TRUTH
Statin causes myotoxicity for Patient
Can’t Capture

17. Practical Clinical Research Informatics
Acknowledgements
Josh Denny
Jeremy Moretz
Josh Peterson
William Bush
Want to learn more?
BSBT6310/BIOS6310 –
Practical Clinical Research Informatics
M. Kahn and L. Wiley
Spring 2019
Funding
Integrated, Individualized and Intelligent Prescribing (I3P) – U01HG007253
Informatics Tools for Pharmacogenomic Discovery Using Practice-Based Data (iPGx) – R01GM103859
VGER, The Vanderbilt Genome-Electronic Records Project – U01HG008672
Genetics Training Grant - T32GM080178
NLM Training Grant – T15LM007450
BioVU:
Vanderbilt CTSA - UL1 TR000445
Instrumentation Award - 1S10RR
Institutional Funding; RC2GM092618; U01HG004603