Automated Surveillancefor Adverse Drug Events at Duke

University Health System

Peter M. Kilbridge, M.D.Washington University School of Medicine

AHRQ Technology and Patient SafetySeptember 26, 2007

2

How can we measure adverse events?• Most organizations: Voluntary reporting is the only

mechanism available• Anecdotal

• Misses the majority of events

• Chart review: • Very resource-intensive

• Variable in effectiveness (e.g., implicit vs. explicit review methodologies)

• Not comprehensive

• Computerized surveillance: effective, but rarely employed• Specialized IT requirements

• Still requires significant clinical resources

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How automated ADE detection works:• Computerized surveillance of patient data

searching for evidence suggesting that an ADE has occurred

• Rules engine uses combinations of data to detect potential ADEs and fire signals

• Signals that fire are investigated by study clinicians to determine causality:whether they represent true ADEs, and if so, grade severity and nature of ADEs.

• Same rules engine for 3 hospitals

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Examples of Surveillance Rules• Antidote ordered/dispensed• Toxic serum drug level• Physiologic parameters changing +

active order for a medication• Heparin AND rapidly falling platelet

count• Nephrotoxic medication AND rising Cr• Hypoglycemia AND D25, D50 ordered• INR > 4 AND active order for warfarin ...

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Scoring Causality and Severity

• Causality:

• Probability that a signal represents a true Adverse Drug Event

• Naranjo algorithm (Clin. Pharmaco. Ther. 1981;30:239-245): Score must be probable or defininte to count as an ADE.

• Severity:

• Duke severity scoring system, 0-6 scale

• Like NCC-MERP, 3 and over equals harm to the patient

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ADE Surveillance: Evaluation Process

Definite or probable?Definite or probable?

Trigger Condition Met

Trigger Condition Met

Independentinvestigation (chart

review, clinician, patient interviews)

Independentinvestigation (chart

review, clinician, patient interviews)

Adverse Event?

Adverse Event?

No

Note to patient chart

Note to patient chart

Grade severityGrade severity Grade causalityGrade causality

Yes

No

Record as AE, causality

unknown

Record as AE, causality

unknown

Follow-up procedures & tracking

• LOS• Outcome• Diagnoses . . .

Follow-up procedures & tracking

• LOS• Outcome• Diagnoses . . .

Inform clinicians that ADE confirmed

Inform clinicians that ADE confirmed

Send to database,

generate reports to P&T, etc.

Send to database,

generate reports to P&T, etc.

Incorporate into patient safety

continuous improvement

cycle

Incorporate into patient safety

continuous improvement

cycle

StartStart

Intervention in care if needed

Intervention in care if needed

Definite or probable?Definite or probable?

Trigger Condition Met

Trigger Condition Met

Independentinvestigation (chart

review, clinician, patient interviews)

Independentinvestigation (chart

review, clinician, patient interviews)

Adverse Event?

Adverse Event?

No

Note to patient chart

Note negative

Possible

Grade severityGrade severity Grade causalityEstablish causality

Yes

No

Record as AE, causality

unknown

Record as AE, causality

unknown

Follow-up procedures & tracking

• LOS• Outcome• Diagnoses . . .

Follow-up procedures & tracking

• LOS• Outcome• Diagnoses . . .

Inform clinicians that ADE confirmed

Inform clinicians that ADE confirmed

Send to database,

generate reports to P&T, etc.

Send to database,

generate reports to P&T, etc.

Incorporate into patient safety

continuous improvement

cycle

Incorporate into patient safety

continuous improvement

cycle

StartStart

Intervention in care if needed

Intervention in care if needed

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Example: Coagulation-Related ADE

• Alert: warfarin and an INR > 4

• Investigation: Adult patient previously admitted for A. fib, discharged on warfarin. Patient returned to the ED 10 days later feeling unwell; while in the ED, vomited 200cc of bright red blood. INR was 12.3. Patient required FFP and vitamin K, and was transferred to the ICU.

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Sometimes we find something else:

• Alert: Naloxone

• Investigation: Patient administered Midazolam 2mg IV and Fentanyl 50 mcg for upper GI, plus ? sprays cetacaine for procedure. Later found unresponsive, hypotensive, with respiratory compromise. Naloxone given with no response. Methemoglobin level =13.7. Patient administered methlyene blue 90mg IV with reduction of methemoglobin level to 1.3.

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DUH ADEs by Category 12 months

0.00

0.20

0.40

0.60

0.80

1.00

1.20

1.40

Ra

te p

er

10

0 A

dm

iss

ion

s

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ADE rates from computerized surveillance 1991-2005:

Classen et al. 1991 2.5 ADEs per 100 admissions

Jha et al. 1998 4.1 “ “

Duke 2005 – 2 hospitals 4.4, 6.3

Gurwitz 2003 50 ADEs per 1000 pt-yrs (ambulatory)

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520

7965

ADE Surveillance Voluntary reporting

Total Inpatient ADEs = 585

ADE Surveillance vs. Voluntary Reporting: 4 months

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DUH ADE Categories by Month

0.00

0.20

0.40

0.60

0.80

1.00

1.20

1.40

1.60

1.80

2.00

2005-02

2005-03

2005-04

2005-05

2005-06

2005-07

2005-08

2005-09

2005-10

2005-11

2005-12

2006-01

Ra

te p

er

10

0 A

dm

iss

ion

s

Anticoagulants

C. difficile colitis

Hyperkalemia

Hypoglycemia

Miscellaneous

Narcotics/Benzodiazepines

Nephrotoxins andIncreased Cr

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One Hospital’s ADEs by Location12 months

0.00

5.00

10.00

15.00

20.00

25.00

N21

N23

N2T

N31

N32

N33

N3R N41

N42

N43

N51

N52

N53

N56

N57

N5N

N5P N5T

N61

N63

N71

N72

N73

N77

N78

N81

N82

N83

N91

N92

N93

Rat

e p

er 1

000

Pt.

Day

s

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ADE rates at two hospitals,6 months, 2005

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Measures to address the problem at problem hospital:

• Clean the rooms of C. diff patients with bleach; switching wipes used on wards to hypochlorite-based product

• Sent letters to MDs, hospital personnel that alcohol foam shouldn't be used for hand hygiene when C. diff a concern; isolation signs updated to include same information

• List of attendings and rooms of patients with C. diff to get a better handle on the problem; feedback as available

• Result:

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C. difficile colitis, 2 hospitals:

0

0.5

1

1.5

2

2.5

3

3.5

March April May June July August September October

C. d

iffi

cile

co

litis

/100

0 p

atie

nt-

day

s

DRH

DUH

Intervention

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Pediatrics vs. Adults (12 mo)

0.00

0.20

0.40

0.60

0.80

1.00

1.20

anticoagulants C. diffi cile colitis hyperkalemia hypoglycemia miscellaneous narcotics/Benzos nephrotoxins

Pediatrics

Adults

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0

2

4

6

8

10

12

14

16

18

20

Analgesic-Narcotic Anticoagulant Antimicrobial Cardiovascular Diuretic Hypoglycemic Immunosuppressant Electrolyte Supplementation Sedative/hypnotic Miscellaneous

VRS

ADE-S

Pediatrics: ADE vs. Voluntary Reporting (12 mo)

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Automated ADE Surveillance: Challenges

• Looking where the light is: we are limited by available data types• Performs consistently across large populations, but is not

comprehensive• Resource requirement for evaluations• How best to use the data on ADE incidence

• Used as a primary measure of medication safety?

• Is it used to design, implement, monitor safety improvements?

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Automated ADE Surveillance: Next Steps

• At Washington University / St. Louis Children’s Hospital:• Use Event Detector expert system to detect ADEs in

pediatric inpatients across SLCH

• Surveillance of pediatric patients with chronic disease in the ambulatory setting and across transitions in care (AHRQ R18 Award):

• Cancer, Sickle Cell Disease, Cystic Fibrosis

• Data from clinic notes (text analysis), pharmacy, laboratory, ED, inpatient and ambulatory EMRs

• New trigger types for these particular patient populations

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Questions?