An Evaluation of Pharmacy Data for Surveillance of ... · An Evaluation of Pharmacy Data for Surveillance of Gastrointestinal and Respiratory Outbreaks Yevgeniy Elbert1, MS Shilpa

An Evaluation of Pharmacy Data for Surveillance of Gastrointestinal and

Respiratory OutbreaksYevgeniy Elbert1, MS

Shilpa Hakre1, MPH, DrPHHoward Burkom2, PhDJulie Pavlin1, MD, MPH

1Walter Reed Army Institute of Research, Silver Spring, MD2Johns Hopkins Applied Physics Laboratory, Laurel, MD

November 15, 2004

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4. TITLE AND SUBTITLE An Evaluation of Pharmacy Data for Surveillance of Gastrointestinal andRespiratory Outbreaks

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Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18

• A U.S. Department of Defense (DoD) system

• Designed to detect infectious disease outbreaks

• Serves military active duty members, their beneficiaries, and retirees

• Uses mainly ICD-9-CM codes from outpatient visits

• Delay of 1- 4 days from patient visit date to data capture date by ESSENCE

INTR

OD

UC

TIO

NESSENCE

Electronic Surveillance System for the Early Notificationof Community-based Epidemics

Pharmacy Data Transaction Service(PDTS)

• Developed by the DoD Pharmacoeconomic Center (PEC) program, managed by WebMD

• Data repository for prescriptions filled by beneficiaries of the military health system

• Approx. 61.1 million prescriptions filled annually1

– 82% of prescriptions from MTFs (n=587) – 18% from:

• Tricare Managed Care Support Contractors Network pharmacies (n=50,000)

• National Mail Order Pharmacy (n=1)

INTR

OD

UC

TIO

N

TricareTricare pharmacy pharmacy transactionstransactions

PDTSPDTS

3.2 seconds

Update every 24 hours

PDTS Fields

• The PDTS formulary and standards maintained through WebMD’ssubscription to the American Hospital Formulary Service (AHFS), the National Council for Prescription Drug Programs (NCPDP), and First Data Bank, Inc.

• Medication id fields in PDTS- Drug name (Label)- Therapeutic class number (GCN)- Therapeutic class code (GC3)- Other

• Previous study by Scott Eader et al. using ESSENCE data for the DC metropolitan area

– Significant positive correlation between outpatient visit and PDTS data for GC3 codes identified for Respiratory (RESP) and gastrointestinal (GI) syndromes

• GC3: developed by First Data Bank, Inc.

3 characters (alpha, numeric, alpha)– organ system, pharmacological class, specific therapeutic

class, respectively

INTR

OD

UC

TIO

N

1.381223731HYPOTENSIVES,ANGIOTENSIN RECEPTOR ANTAGONISTA4F

1.411242950MACROLIDESW1D

1.411247417THIAZIDE AND RELATED DIURETICSR1F

1.431265605GLUCOCORTICOIDSP5A

1.471299466ANTICONVULSANTSH4B

1.481311393ANTI-ANXIETY DRUGSH2F

1.611420677NASAL ANTI-INFLAMMATORY STEROIDSQ7P

1.761557748BETA-ADRENERGIC AGENTSJ5D

1.871654859EXPECTORANTSB3J

1.921700412THYROID HORMONESP3A

2.221966936CALCIUM CHANNEL BLOCKING AGENTSA9A

2.312039720PENICILLINSW1A

2.522230604SELECTIVE SEROTONIN REUPTAKE INHIBITOR (SSRIS)H2S

2.682373543BETA-ADRENERGIC BLOCKING AGENTSJ7C

3.012659102HYPOTENSIVES, ACE INHIBITORSA4D

3.843395463GASTRIC ACID SECRETION REDUCERSD4K

4.313812841ANTIHISTAMINESZ2A

4.584049267LIPOTROPICSM4E

4.814256802ANALGESICS,NARCOTICSH3A

6.345603369NSAIDS, CYCLOOXYGENASE INHIBITOR - TYPES2B

PERCENTPERCENTCOUNTCOUNTDESCRIPTIONDESCRIPTIONGC3GC3

Painkillers

Cholestrolreducers

Allergy relievers

INTR

OD

UC

TIO

NPDTS

Commonly filled medications, 2003

STUDY OBJECTIVES

1) Determine medications commonly prescribed for GI and RESP syndromes during outbreaks

2) Examine trends in daily counts of medications filled for GI, RESP, Asthma visits during outbreaks

3) Conduct retrospective surveillance on drug groups that correlated with GI and RESP outpatient visits during outbreaks

METHODS

• List compiled of known GI and RESP outbreaks

• Commonly prescribed non-refill medications identified for each outbreak– By linking ambulatory and pharmacy data by date of visit/prescription

written and unique encrypted identifiers common to both data sets

• Trends in medications filled and GI/Resp visits investigated during outbreaks– Moving 7-day averages of daily counts

RESULTSOutbreaks

761528Total

1427RESP

621321GI

UnknownBacterialViralNo. of OutbreaksSyndrome

GIOutbreaks

RES

ULT

SG

I Out

brea

k1

SUN MON TUE WED THUR FRI SAT

Field Training Exercise

C 148th Company

35 C company members ill

- Nausea- Diarrhea- Fever- Headache

• Food and water samples from the FTX tested– 5/13 samples tested positive for Campylobacter jejuni

Top 5 ICD-9 codes used during a C. jejuni outbreak

0 10 20 30 40 50 60 70 80 90

Gastroenteritis, noninfctNEC

Diarrhea NOS

Enteritis, viral NOS

Gastritis, acute w/ohemorrhage

Gastritis NOS w/ohemorrhage

558.

978

7.91

008.

853

5.00

535.

50 PERCENT

Top 5 prescriptions written during C. jejuni outbreak

0 5 10 15 20 25 30

Antidiarrheals

Analges ics / antipyretics

Quinolones

Antiem etic/antivertigo agents

Expectorants PERCENTRES

ULT

SG

I Out

brea

k 1

RESULTS

Campylobacter jejuni Outbreak 7-day moving averages

0

5

10

15

20

25

30

35

40

10/1/2002 10/15/2002 10/29/2002 11/12/2002 11/26/2002 12/10/2002 12/24/2002

Date

GI S

yndr

ome

Visi

ts

0

10

20

30

40

50

60

70

80

Med

icat

ions

Fill

ed

GI visits Antiemetics Antidiarrheals Quinolones Antihistamines

OUTBREAK

RES

ULT

SG

I Out

brea

k2

Top 5 ICD-9 codes used during a Salmonella outbreak

0 5 10 15 20 25 30 35

Poisoning, foodNOS

Gastroenteritis,noninfct NEC

Diarrhea NOS

Poisoning, food,bacterial NEC

Gastritis, acute w/ohemorrhage

005.

955

8.9

787.

9100

5.89

535.

00 PERCENT

Top 5 prescriptions during the Salmonella outbreak

0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0 45.0

Antihistamines

Quinolones

Analgesics/antipyretics

NSAID

Antidiarrheals PERCENT

RESULTS

Salmonella Outbreak 7-day moving averages

05

10152025

11/1/2002 11/15/2002 11/29/2002 12/13/2002 12/27/2002

Date

Med

icat

ions

Fi

lled

0510152025

GI S

yndr

ome

Visi

ts

GI Visits Analgesic/antipyretic AntidiarrhealsQuinolones Antihistamines

OUTBREAK

Analgesics/antipyretics: Acetaminophen, Tylenol, etc.Antidiarrheals: Loperamide, Imodium, Pepto-bismol, etc.Antihistamines: Includes Phenergan, Promethazine (antiemetics)Quinolones: Ciprofloxacin, Levaquin, etc.

RESULTSGI OUTBREAK 3

• At a U.S. Air Force training base in Texas3

– Norovirus outbreak– In all 464 trainees affected– Lasted 7 days– 7/7 stool samples tested positive for

Norovirus

Top 5 prescriptions written during a Norovirus outbreak

0 10 20 30 40 50 60

ANTIDIARRHEALS

ANTIHISTAMINES

PERCENT

Top 5 ICD-9 codes used during a Norovirus outbreak

0.00 10.00 20.00 30.00 40.00 50.00 60.00 70.00 80.00

Gastroenteritis, noninfct NEC

Enteritis presumed infct origin

Diarrhea NOS

Nausea with vomiting

Vomiting alone

558.

900

9.1

787.

9178

7.01

787.

03 PERCENT

RES

ULT

S

GI O

utbr

eak

3

RESULTS

Norovirus Outbreak 7-day moving averages

0102030405060708090

1/1/2004 1/22/2004 2/12/2004 3/4/2004 3/25/2004 4/15/2004

Date

GI S

yndr

ome

Visi

ts

010203040506070

Med

icat

ions

Fill

ed

GI Visits Antidiarrheals Antihistamines

OUTBREAK

RESPOutbreaks

RESULTSRESP OUTBREAK 1

• At the Marine Corps Recruit Depot in San Diego3

– Largest Group A Streptococcus outbreak since 1968

– 160 recruits admitted for pneumonia (radiographically confirmed)

– November 1 – December 20– Sputum, blood and throat cultures

• Group A Streptococcus isolated

Top 5 ICD-9 codes used during a Streptococcus A outbreak

0 5 10 15 20 25 30 35

Infct up rsprt mlt sites, acute NOS

Pneumonia, organism NOS

Pharyngitis, acute

Shortness of breath

Cough

465.

948

646

278

6.05

786.

2

PERCENT

Top 5 prescriptions written during a Streptococcus A outbreak

0 5 10 15 20


Expectorants

Sympathomimetic agents

Macrolides

Zinc replacement PERCENTRES

ULT

SR

ESP

Out

brea

k 12

RESULTS

Streptococcus A Outbreak7-day moving averages

0

20

40

60

80

10/15/2002 10/30/2002 11/14/2002 11/29/2002 12/14/2002 12/29/2002

Date

Med

icat

ions

Fill

ed

0102030405060

RES

P Sy

ndro

me

Visi

ts

RespVisits ExpectorantsZincReplacement Analgesics/antipyreticsSympathomimeticAgents

OUTBREAK

Expectorants: Robitussin, Guaifenesin, etc.

Sympathomimetic agents: Sudafed, etc

Zinc replacement: Cepacol Cold Care, etc.

Analgesics/antipyretics: Acetaminophen, Tylenol, etc.

RESULTSRESP OUTBREAK 2

• Influenza in an Advanced Individual Training population in VA in November, 2003– Approx. 187 cases total– Oct. 31st – Nov. 7th

– Rapid flu tests positive; 5 CDC viral cultures Flu A positive, subtyped Korea-like or Fujian-like viruses

Top 5 ICD-9 codes used during an influenza outbreak

0 5 10 15 20 25 30 35

Infct up rsprt mltsites, acute NOS

Bronchitis, acute

Cough

Bronchitis NOS

Pharyngitis, acute

465.

946

6.0

786.

249

046

2 PERCENT

Top 5 prescriptions written during an influenza outbreak

0 5 10 15 20 25 30

Expectorants


Cough and/or coldpreparations

Beta-adrenergic agents

NSAIDS PERCENT

RES

ULT

SR

ESP

Out

brea

k 2

RESULTS

Influenza Outbreak7-day moving averages

0

20

40

60

80

100

120

140

10/1/2003 10/16/2003 10/31/2003 11/15/2003 11/30/2003 12/15/2003 12/30/2003

Date

Med

icat

ions

fille

d

0102030405060708090100

Visi

ts

RespVisits Expectorants Analgesic/antipyretic Antitussives

OUTBREAK

RESULTS

GI groupGI group

1. 1. AntiemeticsAntiemetics2. 2. AntidiarrhealsAntidiarrheals3. Antihistamines3. Antihistamines4. Analgesics/antipyretics4. Analgesics/antipyretics5. Antispasmodics5. Antispasmodics6. Antacids6. Antacids7. 7. QuinolonesQuinolones8. Intestinal adsorbents and 8. Intestinal adsorbents and

protectivesprotectives9. 9. PenicillinsPenicillins

10. Absorbable sulfonamides10. Absorbable sulfonamides

RESP groupRESP group

1. Expectorants1. Expectorants2. Cough and/or cold 2. Cough and/or cold

preparationspreparations3. Analgesics/antipyretics3. Analgesics/antipyretics4. 4. AntitussivesAntitussives, non, non--narcoticnarcotic5. 5. SympathomimeticSympathomimetic agentsagents6. NSAIDS6. NSAIDS7. 7. MacrolidesMacrolides8. 8. QuinolonesQuinolones9. Zinc replacement9. Zinc replacement

10. 10. PenicillinsPenicillins

STUDY OBJECTIVES

1) Determine medications commonly prescribed for GI and Respiratory (RESP) syndromes

2) Examine trends in daily counts of medications for GI, RESP, Asthma visits during outbreaks

3) Conduct retrospective surveillance on GI and RESP syndrome drug groups and GI and RESP outpatient visits at installations where outbreaks occurred

METHODS

• Retrospective surveillance conducted on pharmacy and outpatient visit data for approx. 1 year prior to and including the outbreak timeframe– Regression/Exponential Weighted Moving Average (EWMA) detection

algorithms run on daily total GI/RESP visits, daily total PDTS syndrome groups and each GC3 group → output of p-values

– P-values from individual larger count GC3 groups (>1 prescription in 3 days) were combined using Fisher and Edgington combination p-value methods

• More information on combination p-value methods → Dr. Howard Burkom’s talk at 2:00 p.m.

– Detections with approximately 1 per 6 weeks false alert rate were identified graphically

Salmonella Outbreak(12/9/02 to 12/18/02)

1

11

21

31

41

51

61

71

81

91

10/3

1/20

01

11/1

4/20

01

11/2

8/20

01

12/1

2/20

01

12/2

6/20

01

1/9/

2002

1/23

/200

2

2/6/

2002

2/20

/200

2

3/6/

2002

3/20

/200

2

4/3/

2002

4/17

/200

2

5/1/

2002

5/15

/200

2

5/29

/200

2

6/12

/200

2

6/26

/200

2

7/10

/200

2

7/24

/200

2

8/7/

2002

8/21

/200

2

9/4/

2002

9/18

/200

2

10/2

/200

2

10/1

6/20

02

10/3

0/20

02

11/1

3/20

02

11/2

7/20

02

12/1

1/20

02

12/2

5/20

02

Outpatient Visits ESSENCE Visits EDGINGTON Rx FISHER Rx ESSENCE Rx Outbreak

1

11

21

31

41

51

61

71

81

91

101

3/3/

2002

3/10

/200

2

3/17

/200

2

3/24

/200

2

3/31

/200

2

4/7/

2002

4/14

/200

2

4/21

/200

2

4/28

/200

2

5/5/

2002

5/12

/200

2

5/19

/200

2

5/26

/200

2

6/2/

2002

6/9/

2002

6/16

/200

2

6/23

/200

2

6/30

/200

2

7/7/

2002

7/14

/200

2

7/21

/200

2

7/28

/200

2

8/4/

2002

8/11

/200

2

8/18

/200

2

8/25

/200

2

9/1/

2002

9/8/

2002

9/15

/200

2

9/22

/200

2

9/29

/200

2

10/6

/200

2

10/1

3/20

02

10/2

0/20

02

10/2

7/20

02

11/3

/200

2

11/1

0/20

02

11/1

7/20

02

11/2

4/20

02

12/1

/200

2

12/8

/200

2

12/1

5/20

02

12/2

2/20

02

12/2

9/20

02

Outpatient Visits ESSENCE VISITS EDGINGTON Rx FISHER Rx ESSENCE Rx Outbreak

C. jejuni Outbreak(11/16/02 – 11/18/02)

1

51

101

151

201

251

301

3/3/

2003

3/17

/200

3

3/31

/200

3

4/14

/200

3

4/28

/200

3

5/12

/200

3

5/26

/200

3

6/9/

2003

6/23

/200

3

7/7/

2003

7/21

/200

3

8/4/

2003

8/18

/200

3

9/1/

2003

9/15

/200

3

9/29

/200

3

10/1

3/20

03

10/2

7/20

03

11/1

0/20

03

11/2

4/20

03

12/8

/200

3

12/2

2/20

03

1/5/

2004

1/19

/200

4

2/2/

2004

2/16

/200

4

3/1/

2004

3/15

/200

4

3/29

/200

4


Norovirus Outbreak3

(02/17/04 to 02/24/04)

Norovirus Outbreak(11/25/02 to 12/15/02)

1

21

41

61

81

101

121

3/3/20

023/1

7/2002

3/31/2

0024/1

4/2002

4/28/2

0025/1

2/2002

5/26/2

0026/9

/2002

6/23/2

0027/7

/2002

7/21/2

0028/4

/2002

8/18/2

0029/1

/2002

9/15/2

0029/2

9/2002

10/13

/2002

10/27

/2002

11/10

/2002

11/24

/2002

12/8/

2002

12/22

/2002

1/5/20

031/1

9/2003

Outpatient Visits ESSENCE Visits EDGINGTON Rx FISHER Rx ESSENCE Rx Outbreak

Alerted earlier

1

51

101

151

201

251

301

351

10/31

/2002

11/14

/2002

11/28

/2002

12/12

/2002

12/26

/2002

1/9/20

031/2

3/2003

2/6/20

032/2

0/2003

3/6/20

033/2

0/2003

4/3/20

034/1

7/2003

5/1/20

035/1

5/2003

5/29/2

0036/1

2/2003

6/26/2

0037/1

0/2003

7/24/2

0038/7

/2003

8/21/2

0039/4

/2003

9/18/2

00310

/2/20

0310

/16/200

310

/30/200

311

/13/200

311

/27/200

312

/11/200

312

/25/200

3


Influenza Outbreak(11/1/03 to 11/18/03)

Group A Streptococcus Outbreak12/08/02 to 12/12/02

1

21

41

61

81

101

121

141

161

181

201

12/10

/2001

12/20

/2001

12/30

/2001

1/9/20

021/1

9/2002

1/29/2

0022/8

/2002

2/18/2

0022/2

8/2002

3/10/2

0023/2

0/2002

3/30/2

0024/9

/2002

4/19/2

0024/2

9/2002

5/9/20

025/1

9/2002

5/29/2

0026/8

/2002

6/18/2

0026/2

8/2002

7/8/20

027/1

8/2002

7/28/2

0028/7

/2002

8/17/2

0028/2

7/2002

9/6/20

029/1

6/2002

9/26/2

00210

/6/20

0210

/16/200

210

/26/200

211

/5/20

0211

/15/200

211

/25/200

212

/5/20

0212

/15/200

212

/25/200

2


Alerted earliest

CONCLUSIONS• Use of the GC3 classification system in military pharmacy data

can increase sensitivity without significantly affecting the false alert rate.– A limitation: Certain medications were found in more than one

GC3 group. If these don’t contribute to an outbreak, the signal is weakened

• Outbreaks were characterized by increases in certain GC3 groups and combinations of GC3 groups but these varied by outbreak type.

• Syndromic drug groups were formed using medications more commonly used during outbreaks, increasing the overall sensitivity of the system.

CONCLUSIONS

• The ESSENCE outpatient visit detector, the gold standard, alerted for all 6 outbreaks.

• The ESSENCE pharmacy detector performed well and alerted for 5/6 outbreaks.

• The two p-value combination methods have distinct advantages. The Fisher method alerted for 5/6 outbreaks and was more sensitive to individual GC3 increases. Whereas, the Edgington method alerted for 3/6 outbreaks but was more responsive to consensus and in 2 outbreaks alerted earlier.

• Combination methods are more sensitive and specific if low count gc3 streams are accumulated or dropped.

FUTURE RESEARCH

• Investigate performance of algorithms for other outbreaks

• Investigate performance of detectors for a GC3 group switch, i.e., ignore product groups that don’t meet a certain minimum count

• Continue to investigate product groups that give more signal and less noise

• Prospective surveillance using ESSENCE pharmacy and combination method detectors

REFERENCES

1. http://www.pec.ha.osd.mil/ICD/ICD_MTF_040502.doc

2. Centers for Disease Control and Prevention. Outbreak of group A streptococcal pneumonia among Marine Corps recruits – California, November 1 –December 20, 2002. MMWR. 2003;52(6):106-109.

3. Yamane, GK, Shibukawa-Kent, RL. 2004. A large norovirus GI outbreak among trainees at a USAF training base. Seventh Annual Force Health Protection Conference, Aug. 8-12, 2004.

ACKNOWLEDGEMENTS

CPT Jeffrey K. Brown, USAMRID, Fort Detrick, MD

LCDR Scott Thornton, NEPMU-6, Pearl Harbor, HI

MAJ Samuel Jang, CHPPM, Aberdeen Proving Grounds, MD

Asha Riegodedios, MPH, NEHC, Bethesda, MD

THANK YOUFOR YOURATTENTION

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An Evaluation of Pharmacy Data for Surveillance of ... · An Evaluation of Pharmacy Data for Surveillance of Gastrointestinal and Respiratory Outbreaks Yevgeniy Elbert1, MS Shilpa