You raise a good point. Placebos used in clinical trials are often designed to mimic the active drug as closely as possible in terms of appearance, taste, and other factors to maintain the "blinding" of both participants and investigators and prevent unblinding. Enteric coating a placebo capsule would be consistent with maintaining the blinding in this trial. Of course, there is no way to be certain what group someone is in during a blinded trial.

1. SOCIAL
SOCIAL MEDIA & MOBILE APPS AS SOURCES FOR
PATIENT REPORTED INFORMATION
Nabarun Dasgupta
Epidemico
April 24, 2015
The WEB-RADR project is supported by the Innovative Medicines Initiative Joint
Undertaking (IMI JU) under grant agreement n° 115632, resources of which are
composed of financial contribution from the European Union's Seventh Framework
Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution.
Slides available @epidemico

3. Typhoid cases in Mufulira have
reached 2, 227 with health authorities
calling for increased efforts to prevent
new infections in Mupambe Township.
2, 227
#
Typhoid Mufulira
Mupambe Township

5. Medicine Use
Negative Reaction
Suspected Problem
Require medical attention
Life threatening
Reported
Verified
Patients don't report bad reactions
because they don't know they should.
We can amplify their voices by meeting patients
where they are at and filtering out noise.

6. Patients are speaking
Shouldn’t we be listening?
Beyond informing the public about the
importance of adverse event reporting, we
can take steps to encourage patients to
report.
01 02 03
Meet patients
where they’re at
Protect their
privacy
Give them
easy-to-use
tools

7. Data flow for detecting adverse drug reactions in
social media data.
7
DATA PROCESSING
Acquire
Filter
Curate
Causation
Describe
Collect social
media data
Detect Proto-
AEs, translate
vernacular
Reduce false
positives
Descriptive
statistics
Synthesis
of
information

8. Analyzing social media relies on machine- and
human-dependent processes.
8
WORK SEGMENTATION
SOFTWARE AUTOMATION HUMAN SKILL COMMUNITY
Define questions that matter
Take a systematic approach to selectively analyze
data for drugs and disease where there is a lack
of understanding.
Improve data tools for efficiency
Natural language processing (NLP) and machine
learning tools can assist in reducing human
burden.
CAUSATIONDESCRIBECURATEACQUIRE FILTER

9. Bayesian classifier
identifies posts with
resemblance to adverse
events
Dictionary translates
vernacular to
MedDRA
Multiple copies of
posts are consolidated
and PII removed
01
02
03
50 million posts that mention a medical product
have been collected. The classifier has been
trained with 360,000 manually coded posts.
9
AUTOMATED FILTERING
68%
Research-ready data available
daily.
PRECISION
[+ predictive value]
88%
RECALL
[sensitivity]

10. Vernacular-to-Regulatory
Translation
10

11. Spelling VariationsCombined or invented wordsImplied phrasesInternet Vernacular Translation
lost their eyesight
seeing weird color
seeing weird colour
doublevision
uldn’t see
double vision
blind
googley eyed
blurry vision
changes in viscross eyed
seeing weird
vision change
blindness
cross visionvisual snow
googly eyed
seeing doub
making me eat like a mouse
anorexic
st appetite
#notevenhungry
appetite is nonexistent
apetite surpressed
didn’t get hungry
dont want to eat
killed my apetite
miss feeling hung
killed my appetite
can’t eat
lost apetite
lost my appetite
no appetitey
lack of apetite
stomach small
lost teh appetite
never hnever want to eat
cant eat
coucrosseyed
blurry
apetite surpressed
killed my apetite
lost apetite
lack of apetite
lost teh appetite
Typos
seeing weird color
seeing weird colour
googley eyed
googly eyed
#notevenhungry
no appetitey
making me eat like a mouse
never want to eat

12. Visual impairment
MedDRA 10047571
Visual impairment
SNOMED 397540003
Decreased appetite
MedDRA 10061428
Loss of appetite
SNOMED 79890006
making me eat like a mouse
anorexic
st appetite
#notevenhungry
appetite is nonexistent
apetite surpressed
didn’t get hungry
dont want to eat
miss feeling hung
killed my appetite
can’t eat
lost apetite
lost my appetite
no appetitey
lack of apetite
stomach small
lost teh appetite
never hnever want to eat
cant eat
lost their eyesight
seeing weird color
seeing weird colour
doublevision
uldn’t see
double vision
blind
googley eyed
blurry vision
changes in viscross eyed
seeing weird
vision change
blindness
cross visionvisual snow
googly eyed
seeing doub
coucrosseyed
blurry
killed my apetite

13. 1067
0
0
118
448
15
0
37
2
1
44
4
PROS
0
0
3972
387
356
12
0
15
0
1
55
5
CONS
0
0
47
0
0
1
0
0
27
1
0
PROS
0
0
115
4
0
4
0
0
113
6
0
CONS
XanaxXanax and Hydrocodoneand HydrocodoneXanax and HydrocodoneHydrocodone isand Hydrocodone isHydrocodone is like blackouta blackouthaving a blackoutblackout withouta blackout withoutblackout without the drinkingthe drinkingwithout the drinkingdrinking andthe drinking anddrinking and the
hangoverthe hangoverand the hangover
Xanax Hydrocodone blackout
hangover
and is like having a without the drinking and the

14. PRO CON
COMPOSITE
SCORE
0.8208
Xanax Hydrocodone blackout
hangover
and is like having a without the drinking and the

15. • Victoza® - liraglutide [rDNA origin] injection
• Diabetes indication
• (Does not include Dec 2014 US approval for Saxenda® for chronic obesity)
• UK, US, IN, CN, EU, JP, DE, DK, NL, IE, SE, FR, MY, SG
• UK approval: 30 Jun 2009
• Public Social Media (FB & Twitter): Jan 1, 2014 to March 9, 2015
• English language only
• MHRA Drug Analysis Print & FDA FAERS (county-limited, non-duplicated)
15
• DESCRIPTIVE METHODS

16. Relevant events in Victoza® (liraglutide) history and current analysis
16
VICTOZA TIMELINE
2009
2010
2013
2014
UK
APPROVAL
June 30
SOCIAL MEDIA DATA
COLLECTION BEGINS
January 1
2015
STUDY END
March 9
EARLIEST MHRA
MENTION?
March 21
2001
//
OBSERVATIONAL
STUDY
PUBLISHED
April 8
US
APPROVAL
January 25
FAERS DATA
AVAILABLE
October 1
2012

17. Victoza only
17
Descriptive Analysis

18. 10,458
All public mentions
of Victoza or
liraglutide in
Facebook or
Twitter, arising from
7,150 unique posts
ACQUIRE
368
Total number of
posts resembling
adverse events
(Proto-AEs) after
curation.
3.5% of mentions
are Proto-AEs
FILTER
158
False positive posts
removed by manual
curation
30%
CURATE
699
Drug-event pairs at
the MedDRA
preferred term level
DESCRIBE
18
OVERALL RESULTS

19. 19
MENTIONS & PROTO-AEs
6360 4098
29 411
TWITTER
All mentions
FACEBOOK
All mentions
TWITTER
Proto-AEs
FACEBOOK
Proto-AEs
01
02
03
04

20. 20
SOC Comparison UK & US Spontaneous Reports

21. 21
QUANTIFYING EVENTS

22. 2 4 2 10
1
2
3
4
5
Pancreatitis Hypersensitivity Angioedema Haemorrhage
The EMA’s list of Important Medical Events (IME)
can be used to identify posts of greatest medical
consequence
22
IMPORTANT MEDICAL EVENTS
2.0%
Posts with IME

23. 23
KNOWN FREQUENCY ADVERSE EVENTS
1:10k+1:1000 1:10k1:1001:10
10
10
0
1k
VERY COMMON
decreased blood sugar
levels, diarrhoea,
nausea
COMMON
bronchitis, constipation,
abdominal distension,
faster heart rate, feeling
dizzy, flatulence,
gastritis, gastro-
oesophageal reflux,
headaches, indigestion,
inflammation of
nose/throat, injection
site problems, loss of
appetite, antibodies to
Victoza, skin rash,
stomach pain, tiredness,
toothache, vomiting
UNCOMMON
dehydration, malaise,
itching, kidney
problems, urticaria
RARE / VERY RARE
anaphylaxis, angioedema, GI
problems; pancreatitis,
hypersensitivity
10
k
SOURCE
emc+ Medicine Guide, Jan 16, 2015, Datapharm
medicines.org.uk
Medicine Guide
Preferred terms appearing in social media and not appearing

24. 24
7.7%
Posts with HSI
“I've been on Victoza for a total of 17
days now for pre-diabetes. After the 5th
day the nausea hit and it's horrible. I'm
afraid to eat anything and the smell of
fried foods kill me. I started on 0.6 for 7
days and now I'm up to 1.2.....when
does it get better? My Dr
recommended that I go back to 0.6 for
a couple weeks to see if it helps. I feel
nauseous, bloated, stomach hurts,
dizzy at times......I have lost weight
(which for me is a good thing ) but it's
not good enough to keep feeling so
horrible. Anyone have any suggestions
for the nausea and bloatng?”
Facebook, January 23, 2015
HEALTH SYSETM INTERACTION

25. 25
IN THEIR OWN WORDS
Typical
Proto-AEs
& Patient
Benefits
@user I just restarted
taking victoza which made
me so sick to my stomach
till my body got used to it.
Aside from the nausea
(worse today) and
occasional bouts of
hypoglycemia (better
today), four days on
Victoza and down 5.3 lbs!
Amazing!
Twitter, May 3, 2014
Facebook, December 9,
2014

26. 26
IN THEIR OWN WORDS
Product
Quality
Issues
Anyone else having issues
with plugger jamming on
their flex pen of victoza?
The only difference I see is
the new needles . I had to
stick myself 4 times today
to get almost a full dose.
Frustration. Doesn't seem
related to where I am into
pen, first dose, midway ,
last. Third pen this has
happened on in a row
Facebook, December 9, 2014

27. 27
IN THEIR OWN WORDS
Product
Tampering
I was curious and wanted to
see how much of Victoza
was left in the [device] after
was gone. I had taken a
syringe and extracted out the
last amount of it. I took out
20 unites out of the pen
remaining. That is well over
one more dosage that could
be used before throwing the
pen away. The money we
pay, feels like we are wasting
a shot that should be there.
Facebook, March 1, 2015

28. 28
IN THEIR OWN WORDS
Diversion &
Re-Sale
I have 2 boxes of victoza
insulin pens if interested
inbox for more information
Facebook, February 3, 2015
Please, if anybody is on
Victoza for diabetes or insulin
resistance < i ordered too
much stock and it is non
returnable being a fridge item
> please pop in at [redacted]
pharmacy .....will organise a
good price to compensate for
my blunder.
Facebook, February 27, 2015

29. 29
IN THEIR OWN WORDS
Product
Pricing
Just bought 4 Victoza pens
from my pharmacy (CVS).
$800 out of pocket. Uggg. :(
Facebook, February 6, 2015

30. 30
IN THEIR OWN WORDS
Off-label
Use
Had my first injection of
Victoza. So if it doesn't kill
me from one of side effects
my sugar should stabilize.
One side effect is puzzling.
"For type 2 Diabetics only.
Not intended for type 1
diabetics". I'm the poster
child for type 1 Diabetics.
Facebook, February 6, 2015

31. 31
IN THEIR OWN WORDS
Pancreatitis
sorry it took awhile..just got out of
the hospital...the new diabetes
doctor that I have took me off the
Victoza....I'm not sharing this to
start a war or panic but listen up
please: I'm an RN and I was on
VICTOZA. I got deathly sick off it,
and developed Pancreatitis really
bad! It was the most painful thing
I ever went through and will
NEVER use Victoza again!!
Anyone else ever had the same
thing I had?
Facebook, February 6, 2015

32. “FDA reevaluated more than 250 toxicology studies
conducted in nearly 18,000 healthy animals (15,480 rodents
and 2475 nonrodents). Microscopic examinations from these
toxicology studies yielded no findings of overt pancreatic
toxic effects or pancreatitis.”
“A pooled analysis of data from 14,611 patients with type 2
diabetes from 25 clinical trials in the sitagliptin database
provided no compelling evidence of an increased risk of
pancreatitis or pancreatic cancer.”
"Both agencies agree that assertions concerning a causal
association between incretin-based drugs and pancreatitis
or pancreatic cancer, as expressed recently in the scientific
literature and in the media, are inconsistent with the current
data.The FDA and the EMA have not reached a final
conclusion at this time regarding such a causal relationship.
Although the totality of the data that have been reviewed
provides reassurance, pancreatitis will continue to be
considered a risk associated with these drugs until more
data are available; both agencies continue to investigate this
safety signal."
32
INFORMATION SYNTHESIS
JAMA Internal Medicine, Vol. 173 (No. 7), Apr 8, 2013
New England Journal of Medicine, Vol. 370 (No. 9), Feb 27, 2014

33. 33
IN THEIR OWN WORDS
Causation?
Follow-up?
I saw the Endocrinologist today
and will need a biopsy on
Thyroid, for one of the 3 nodules (
I will call them my triplets, lol)....
Lot's of prayers and positive
thoughts would be welcomed. I'm
slightly nervous because I have
been taking Victoza and the side
effect is Thyroid Cancer.... Damn
it. So hoping and wishing that it's
just a big coincidence of timing....
Deep breaths and sweet
dreams..... :)
Facebook, April 2, 2014

34. 2
23
21
158
TWITTER
MHRA spontaneous reports
FDA spontaneous reports (w/o multiplicate reduction)
FACEBOOK
34
REPORTING BURDEN PER MONTH
?
True Incidence Rate?
How does social media volume
for Victoza (liraglutide)
compare to traditional pharmacovigilance?
Can patterns be detected sooner?
What does social media contribute?
Twitter & Facebook: Jan ‘14 – Mar ’15
MHRA Drug Analysis Print: Jun ‘09 – Mar ‘15
FDA FAERS: Oct ‘12 – Mar ‘14

35. 35
CLINICAL TRIAL DISCUSSION
I'm in a Pfizer double blind ######### trial and could receive the
placebo up until week 16 at which point I'm guaranteed to receive
the drug.
What I don't understand is that I can't be told if I was on the
placebo for the first 16 weeks. I'm not seeing any positive benefit
from whatever I've been taking for 8 weeks so far, and I would
really like to know at week 16 if it's the drug because then I can
bail from the study at that time and move on to something else…

36. 36
CLINICAL TRIAL DISCUSSION
He started on Thursday. He told me yesterday that he tried to chew a
capsule (I'm not sure why, I think he wanted to see if it had a flavor) & it
was hard as a rock. I'm assuming maybe it was eneric coated or
something. He took the no flavor to mean he's on the placebo, but I
actually wonder if they would bother enteric coating a placebo.
Probably doesn't matter & I know we're not supposed to know anyway,
just wondered if anyone else's was enteric coated.

37. 37

38. 38
LIMITATIONS OF SOCIAL MEDIA
CAUSALITY
Patients may not correctly assess
causality. Define methods to
measure probability of real world
significance.
VOLUME
Volume of reports likely to be large.
Reduce false positives and create
automated tools to triage
information.
SIGNAL DETECTION
Very limited statistical methods to
detect problems. Collaborate with
academia, industry and regulators to
refine methods.
PRIVACY
Patient privacy expectations and
fear of government oversight. Use
publicly available data only.
REGULATION UNCLEAR
When is there an obligation to
monitor or report? Work with
regulators and industry to clarify
guidance.
01
02
03
04
05

39. 39
QUESTIONS?
web-radr.eu
@WEBRADR
epidemico.com
@epidemico
demo.medwatcher.org
@med_watcher
nabarun@epidemico.com