Presentation by Nabarun Dasgupta at the Drug Information Association (DIA) EudraVigilance Day, London, May 2012. Covers HealthMap, MedWatcher and other research at the intersection of social media, data mining and crowdsourcing in health. Applications are presented in infectious disease (outbreak) surveillance and medical product adverse event safety (drugs, vaccines, devices).

1. MedWatcher, Mobile Phones and
Crowdsourcing for Drug Safety
Surveillance
Nabarun Dasgupta
University of North Carolina at Chapel Hill
John Brownstein
Clark Freifeld
Harvard Medical School
Children’s Hospital Boston

2. About Us
• Our group
– Public health informaticians, epidemiologists, clinicians, computer
scientists and software developers
– Based at Children’s Hospital Boston and Harvard Medical School
– Collaborate with University of North Carolina at Chapel Hill
• Our philosophy
– Rapid prototype development
– Agile/iterative design
– Implement fully operational software
• Our mission
– Improve public health through awareness and access
– Develop public health tools used by millions

3. Computational Epidemiology Group - CHB
• HealthMap platform and derivative products (web and
mobile)
– Key functions: Data Mining, Crowdsourcing, Visualization
– Pioneers in integration of complex health, location data into
consumer-friendly products
– MedWatcher, Flu Near You, Outbreaks Near Me, Google Vaccine Finder
– These apps are views of a common set of underlying tools and methods
• Diverse set of collaborations via specialized data feeds &
displays
– Novartis, Boeringher Ingelheim, Unilever, SAIC, NEJM, Booz Allen, USAID, DoD,
HHS, CDC, FDA

4. Epidemico (CHB Affiliated Company)
Adverse Events Drug X
• Consulting, reports and custom software
• Industry: StreetRx, GulfMedic, Media GRIID
• Government: NEDDS, BioSense, MedWatcher
• Strengths: rapid development, domain expertise,
industry contacts, sales expertise, positive
revenue

5. EMA GVP Module VI
VI.B.1.1.4. Information on suspected adverse reactions from the
internet or digital media
•Marketing authorisation holders should regularly screen internet or digital
media under their management or responsibility, for potential reports of
suspected adverse reactions.
•Unsolicited cases of suspected adverse reactions from the internet or
digital media should be handled as spontaneous reports. The same
expedited reporting time frames as for spontaneous reports should be
applied.
•It is also recommended that the marketing authorisation holder actively
monitor special internet sites or digital media such as those of patients’
support or special diseases groups in order to check if they describe
significant safety issues which may necessitate reporting
•Although not exhaustive, the following list should be considered as digital
media: web site, web page, blog, vlog, social network, internet forum, chat
room, health portal.
Drug Information Association www.diahome.org 5

6. Guangzhou Baiyunshan Pharmaceutical Co.
(Public Shenzhen: 000522.SZ)
January 2003 March 2003

7. Traditional Public Health Reporting
1
1 2
2 3
3 4
4 5
5
Public Public Local Ministry World
health Officials of Bodies
Public Public Local Ministry World
practitioners Health (UN, WHO,
health Officials of Bodies
FAO, OIE)
practitioners Health (UN, WHO,
Labs FAO, OIE)
Healthcare
workers,
Labs
Clinicians
Healthcare
workers,
Clinicians

8. 1 2 3 4 5
5
Public Public Local Ministry World
Digital
health Officials of Bodies
Disease World
practitioners Detection Health (UN, WHO,
Bodies
FAO, OIE)
(UN, WHO,
Labs FAO, OIE)
Healthcare
workers,
Clinicians

9. Emerging and re-emerging infections, 1996-2010
Cryptosporidiosis West Nile Virus Lyme Borreliosis
Human Monkeypox Legionnaire’s Disease Echinococcosis
E.Coli O157 Severe Acute Respiratory Diphtheria
Venezuelan Equine Encephalitis Syndrome (SARS) Influenza A (H5N1)
Dengue Haemorrhagic Fever Malaria Nipah Virus
Ebola Haemorrhagic Fever Typhoid RVF/VHF
Marburg Haemorrhagic Fever Cholera O’Nyong-Nyong Fever
Ross River Virus BSE Buruli Ulcer
Hendra Virus Lassa Fever Multidrug Resistant Salmonella
Reston Virus Yellow Fever nvCJD

10. Number of days from outbreak start to
outbreak discovery
in 1996
167
days
200
Time in Days
150
in 2010
100
50
20days
0
1996 2000 2004 2008
Year of Outbreak Start
Chan et al. 2010. Proceedings of the National Academy of Sciences.

11. Potential of Digital Disease Detection
epidemic curve Blogging
Emailing
Internet Chatting
SMS Messaging
Video/Radio Reporting
Social Networking
Micro Blogging Online News Reporting
Internet Searching Health Expert Reporting

15. HealthMap Overview
• Goal to provide comprehensive overview of global state of
infectious diseases
– Freely available, automated system (24/7)
– Integrates outbreak data from ‘official’ and ‘unofficial’ sources
– Aggregates data by disease & location
– Displays alerts from 29 sources in 10 languages (auto translated)
– Resource for both public health professionals and general population

16. the number of public and private sources we use
to access more than 50,000 sites
10
in
languages
resulting in every hour
24/7
alerts per day
precisely placed in
locations

17. Articles are scanned for key information using
natural language processing
Typhoid cases in Mufulira have
reached 2, 227 with health authorities
calling for increased efforts to prevent
#
new infections in Mupambe Township.
Township

18. 10,500 220
species
locations
Case and
4800 # Death Counts
disease patterns

19. Bayesian Articles are categorized using more
Filtering than 19 million phrases
with
91%
accuracy
Breaking News
Warning
Old News
Context
Not disease related

20. Bayesian Articles are categorized using more
Text matching, similarity score, and rating value
Filtering than 19 million phrases
determine the significance of the alertwith
91%
accuracy
Breaking News
Warning
Old News
Context
Not disease related

21. HealthMap Users - Over 1 million visitors
per year
HHS Command Center ECDC Command Center Liberty Science Museum, NYC
Top Visitors: • CDC
• WHO
• National, state, local public health depts
• NGOs
• Museums
• Clinicians
• Travelers

24. Global spread of H1N1 with informal
sources
Brownstein et al. 2010. New England Journal of Medicine.

25. Professional social networks to support
disease reporting
Human networks has
proven value
Professional networks play
key roles in discovery and
validation
2 Examples:
ProMED ISID
GeoSentinel ISTM

26. Professional Networks and Epidemic
Intelligence

28. Collaborations
Automated Feed Automated Extraction
Community Input
Added Value
(1) Discovery of new content
(2) Provides two-way contextualization
(3) Validation studies

29. Next Generation Public Health:
Participatory Epidemiology

31. HealthMap
Outbreaks Near Me

32. HealthMap
Outbreaks Near Me
Launch
Map List Submit News About

33. > 500k downloads

34. Android
Potential for increased global coverage

35. HealthMap Hotline
919-MAP-1-BUG (627-1284)
Leave a voicemail or Send SMS

37. Reporting through the website

40. worldwide user submitted reports

42. Google Dengue Trends

45. flunearyou.org

46. APHA Challenge
Individual Group
Top Awards Top Awards
Awarded to top three individuals with Awarded to top three groups with
highest total number person-forms highest total number person-forms
divided by number of persons
in group
Minimum Threshold eligibility: Minimum Threshold eligibility:
10,000 person-forms 100,000 person-forms
(one form allowed per person per week) (one form allowed per person per week)

50. HealthMap Flu Vaccine Finder
Drug Informationwww.diahome.org
Association 50

51. Google Flu Vaccine Finder

55. Participatory Epidemiology
Beyond Infectious Disease
Drug Informationwww.diahome.org
Association 55

56. Using search volume to estimate abortion rates
Reis and Brownstein. PLoS One. 2010.

57. Internet users seek out information on quitting and cheap
cigarettes in response to the SCHIP cigarette tax increase.
Ayers, Ribisl, Brownstein. PLoS One. 2011

58. Social Networking and Patient Data
Real time group and individual measurement of
outcomes, treatment side effects, adverse events

59. App for clinicians & consumers
focused on two-way
communication
• Submit adverse event to FDA
• See latest safety alerts
• Post reviews as a patient
• Read reviews

60. Traditional Product Safety Reporting
1
1 2
2 3
3 4
4 5
5
Public Public Industry Regulatory World
health (Pharma, Agencies Bodies
Public Public Industry Regulatory World
practitioners Devices) (FDA, MEB) (WHO, EMA)
health (Pharma, D Agencies Bodies
practitioners evices) (FDA, MEB) (EMA, WHO)
Healthcare Journal
workers, Pubs
Journal
Clinicians
Healthcare Pubs
workers,
Clinicians

61. 2 3 4
5
5
1
Public Public Industry Regulatory World
Digital World
health (Pharma, Devices) Agencies Bodies
Disease Bodies
practitioners Detection (FDA, MEB) (WHO)
(EMA, WHO)
Journal
Pubs
Healthcare
workers,
Clinicians

62. Mobile Technology, Social Networks
and the Future of Medicine
 About 169 million US adults (72% of all adults)
went online to research a health question in
2010, compared with 63 million in 2002
 75% of US physicians own an Apple mobile
device (iPad, iPhone, iPod)
Sources: Manhattan Research Cybercitizen Health U.S. 2011; Taking the Pulse U.S., v11.0. 2011
62

63. The Transition to Mobile
Sources: comScore, Flurry Analytics
63

64. The Current State of Safety
• Adverse event reporting to FDA is largely by manufacturers
– 98% of AE reports for medical devices from manufacturers
– 80% of drug serious AE reports from pharmaceutical companies
– 25% of vaccine AEs from the parents/patients via online portal or paper fax
• Fragmentation of regulatory agencies collecting & analyzing data
– AERS: Drug AEs by Center for Drug Evaluation Research at FDA
– MAUDE: Medical device AEs by Center for Devices & Radiologic Health at FDA
– BPDR: Biological product deviations by Center for Biologics Eval. & Res. at FDA
– VAERS: Vaccine AEs by CDC
– Shortages: to FDA via email
“Pharmacovigilance suffers from bureaucratic
sclerosis. Instead of the system being a lively,
engaging, dynamic, collaborative, humane
enterprise, sharply focused on improved therapy
and the welfare and safety of patients, it is a
sluggish routine that fails to excite and motivate.
Forms are dispiriting, formality is alienating,
distance is subversive.”
– Bruce Hugman, WHO Uppsala Monitoring Center
Sources: Duggirala 2012; Haber 2011; Moore 2007

66. MedWatcher & Public Health
• MedWatcher goals:
– Increase public’s access to drug, device and vaccine information
– Engage consumers to report on their own health
– Engage clinicians to report adverse events
• Free easy to use app across all mobile platforms
• Allows for rapid reporting of suspected adverse events (3 minutes)
• Create sense of community around a drug and disease
• Hypothesis generation for researchers
• Integrate with existing clinical workflows (EHR, etc.)
• Platform for risk management
– Adherence monitoring, interactive safety messaging for patients,
registration/certification for prescribers, enhanced surveillance

67. Drugs, Vaccines, Devices
67

68. 2 Line Simplified Label Information
• Patients care about:
– Safety 87%
– Side effects: 78%
– Comparative prices:
50%
– Time on market: 40%
• Simplified labels for
devices, vaccines, etc.
being developed
Source: Consumer Reports National Research Center 2010
68

69. Detailed Label Information
69

70. Save Products of Interest
70

71. 3 Minute Consumer AE Reporting
71

72. 3 Minute Consumer AE Reporting
72

73. 3 Minute Physician AE Reporting
73

74. 3 Minute Physician AE Reporting
74

75. System Architecture

76. Product Safety Alerts
76

77. Official Information News Sources
Aggregating Information
Peer-review Publications Industry Updates

78. Data Curation
• Secure portal for
human review of AE
submission
• Triage step before data
are imported into
regulatory databases
• Assisted with machine
learning
• Improve quality
• Reduce noise

79. Admin Panel for Aggregating Across
Multiple Sources

80. Medical Counter Measures
• App ideally in wide use before the emergency
• Modular set of detailed questions for reporter
can be inserted into app and deployed
instantly
• Specific medical devices
– Ventilators
– Defibrillators
– Leads
– Large infusion pumps and insulin infusion pumps

81. • Launched prototype in
iTunes in October 2010
• Over 30k downloads
• Top downloaded medical
app for month of launch
• No promotional efforts
• Dozens of AE reports
received
• Redesign & launch 2012

82. Actual Report Submitted via
MedWatcher
• 87 year-old male
• Dx: metastatic prostate cancer and spinal cord
compression
• Tx: Casodex (bicalutamide) 50 mg/day
• LFTs normal at initiation of therapy
• AE: Fulminant hepatic failure after 3 weeks of therapy
(synthetic fx preserved, but jaundice and transaminitis)
• Death 5 weeks after initiation of therapy
• Death certificate only lists prostate cancer as COD
– Direct reporting circumvents misclassification where there
was suspicion of an association with the drug
• “Pt was my father. I am a NP.”

84. Updating the App
• Contracted by FDA to
develop app into official
mobile reporting platform
March 2012
• Expand support for
medical devices and
vaccines
• Updated MCM capabilities
• Universal cross-platform
functionality
• Improved user interface
and simplified forms
• GPS and photo
attachments

85. Online Media and Pharmacovigilance
For Controlled Substances
Drug Informationwww.diahome.org
Association 85

86. Media Monitoring
 Collect electronic
news media reports
from 40,000+ news
sources
 Automated
identification of
articles with drug
names
 Semi-automated
classification of AEs
 Visualization and
statistical aberration
detection

87. News Media AE Monitoring
Source: Dasgupta N, Mandl K, Brownstein JS. PLoS One, 2009

88. Filtering Data to Find Signals
Drug Information Association www.diahome.org 88

89. Crowdsourcing Drug Information
89

90. Uses of street price data
 Understand differences in formulation
strategies
 Understanding nature of drug markets
 Monitoring by DEA, FDA and pharma industry
 To track differences between drugs
 Evaluating the impact of policy
 Early warning system for pharmacies

91. 91

92. 92

93. 93

94. Mapping Black Market Prices

95. Integrated Risk Management
Armed Robbery - CVS Pharmacy
7550 W. Perkins Pl.
Milwaukee, WI
September 9, 2011: Dr. Jack
Allen, a Louisville family care
doctor, was recently placed on
probation by the Kentucky
Board of Medical Licensure
read more…
San Diego, CA Street Prices

96. Temazepam Reformulation in UK
• Temazepam used for sleep, anxiety
• 1980s: Liquid-filled gel capsules
• Late 1980s: Reports of widespread IV injection
• HO requests withdrawal of liquid-filled gel caps
• 1989: Manufacturers reformulate with Gelthix®
– Solid gel capsules (high MW crystaline waxes)
– Called “abuse-resistant” by industry, gov’t, docs
• Reduction in intravenous injection
Drug Information Association www.diahome.org 96

97. Temazepam in UK
• 1991-1992: Reports of intra-arterial injection
• 1992-4: Severe ischaemic damage
– Amputations, DVT, muscle necrosis, fasciotomies
• 1996: Temazepam capsules removed by NHS
Drug Information Association www.diahome.org 97

98. Tamper-Deterrent Formulations
Deterrence Approach Example
OxyContin
Physical Barrier
OC vs OP
OROS Concerta vs
Physical Barrier
Ritalin
Agonist-Antagonist Suboxone vs Subutex
Prodrug Vyvanse vs Adderall
Drug Information Association www.diahome.org 98

99. Example 1: OxyContin
OxyContin (controlled-release
oxycodone) indicated for
around-the-clock moderate to
severe chronic pain
Documented tampering for
euphoric effect of traditional
formulation (OC)
Newer formulation (OP) is more
difficult to crush for injection or
snorting
Launched August 2010
Rapid change in
pharmaceutical
distribution supply chain
99

100. Analytic Methods
• Include data where formulation was specified
• Exclude “cheap” or “overpriced” outliers
• Standardized by milligram strength
• StreetRx: Nov 1, 2010 through April 24, 2011
• Drug Diversion: 4th quarter 2010
• Geometric means and 95% confidence
intervals
– Similar to median & IQR for skewed distributions
• Percent mean price difference between OC
and OP
100

102. Example 2: Rx Stimulants
• Stimulant medications indicated for attention
deficit hyperactivity disorder (ADHD)
• Adderall and Adderall XR are amphetamine
salts
• Vyvanse is a prodrug, lisdexamfetamine
– D-amphetamine bonded to L-lysine
– Oral consumption and subsequent metabolism to
active form (D-amphetamine)
• Approximate clinical conversion 1:3
102

103. 103

104. Deterrence Approach Example $ Difference
Agonist-Antagonist Suboxone vs Subutex 14% to 17%
OxyContin
Physical Barrier 26% to 29%
OC vs OP
OROS Concerta vs
Physical Barrier 42%
Ritalin
Prodrug Vyvanse vs Adderall 52% to 60%
104

105. EMA GVP Module VI
VI.B.1.1.4. Information on suspected adverse reactions from the
internet or digital media
•Marketing authorisation holders should regularly screen internet or digital
media under their management or responsibility, for potential reports of
suspected adverse reactions.
•Unsolicited cases of suspected adverse reactions from the internet or
digital media should be handled as spontaneous reports. The same
expedited reporting time frames as for spontaneous reports should be
applied.
•It is also recommended that the marketing authorisation holder actively
monitor special internet sites or digital media such as those of patients’
support or special diseases groups in order to check if they describe
significant safety issues which may necessitate reporting
•Although not exhaustive, the following list should be considered as digital
media: web site, web page, blog, vlog, social network, internet forum, chat
room, health portal.
Drug Information Association www.diahome.org 105

106. Thank you!
healtmap.org
medwatcher.org
nabarun@epidemico.com
Drug Information Association www.diahome.org 106