1. Participatory medicine and using
Patient Reported Outcomes to inform
Off-Label Prescribing
Jeana H Frost
Communicatie, Amsterdam Center for Social Media
VU University Amsterdam

2. Previous work:
Interested in patient-led inquiry into health
(graduate school, PLM, VU)
Psychology, learning sciences, communications

3. Talk:
1. Understudied indications: Off-label prescribing
2. The opportunities available to collect data from
patients to inform medical practice
3. Example: Evaluation of one data set of off-label
use

4. Off-label prescribing
• Before a drug is brought to market in the U.S.,
Federal Drug Administration (FDA) legislates 3
phases of testing including efficacy testing for a
single purpose
• Once a drug is brought to market, physicians
are free to prescribe drugs for both the tested
purpose and for “off-label” purposes/indications
although pharmaceutical companies cannot
promote off-label uses

5. Current situation
• Clinicians are innovators
testing novel uses of existing
drugs within their practice
(Demonaco, Ali, & von Hippel,
2006)
• Patients increasingly are
forcing and even steering
this innovation

6. Current situation
• 21% of treatment instances are off-label
• 73% based on little to no scientific
evidence(Radley, Finkelstein, & Safford,
2006)
Why?

7. The cost of gathering evidence
• $15,700 per patient phase 1 trial
• $26,000 phase 3 (Goldfarb, 2006)
• $100 – 800 million to bring a drug to
market (Fee, 2007)
• Drugs are commonly off-patent
• Possible disincentive, could remove an
existing product line

8. The cost of not doing so…
Patients at risk of unnecessary and even harmful
treatments
One example:
In one year (2002), 63% of 392,000 terbutaline
prescriptions were for pregnant women (Young,
Adams, 2003)
No demonstrated benefits and instances of real
harm (Haas, 2007; Nanda et al, 2002; CTAF, 2002)

9. Evidence is lacking but individual
experiences are not.
Opportunity to collect patient outcomes

10. Convergence of factors
1. Patient Reported Outcomes (PROs)
2. Patients going online
3. People adding personal data to larger
databases online

11. 1. Patient Reported Outcomes (PROs)
• Have strong prognostic value (Rothman,
2007)
• Less prone to memory bias (Hufford,
2002)
• Provide a sense of anonymity to research
subjects and are less vulnerable to
misrepresentation of sensitive topics
(Turner, 1998)

12. 1. Patient Reported Outcomes (PROs)
• Food and Drug Administration (FDA) and
the European Medicines Agency (EMEA)
have released guidelines on how to
standardize PROs for use within research
and drug labeling.
• Usage of PROs common in domains
ranging from oncology (Basch, 2009) to
allergy treatment (Baiardini, 2010)

13. 2. The Rise of ePatients
• 74% of American adults go online
• 61% of adults look online for health
information, termed "e-patients”
(Fox, 2009)
Similar access in the Netherlands

14. 2. The Rise of ePatients
Health consumers are interested in patient
generated information, of e-patients…
• 41% have read someone else's commentary or
experience about health or medical issues online
• 24% have consulted rankings or reviews online
of doctors or other providers.
• 24% have consulted rankings or reviews online
of hospitals or other medical facilities.
(Fox, 2009 - Pew Internet and Life)

15. 2. The Rise of ePatients
But few are actively writing or creating new health
content: of e-patients …
• 6% have tagged or categorized health or medical content
• 6% have posted in an online discussion, listserv, or other online group
forum.
• 5% have posted comments about health on a blog.
• 5% have posted a review online of a doctor.
• 4% have posted a review online of a hospital.
• 4% have shared photos, videos or audio files online about health or
medical issues.
In sum, 37% of adults, or 60% of e-patients, have done at
least one of the above activities.
(Fox, 2009 - Pew Internet and Life)

16. An aside: Benefits to patients of
participating in online discussions
• Patients learn from one another not only “medical”
information but also how to live with a condition
(Hoch)
• Participation heightens levels of knowledge, well-
being, and empowerment
(Barak et al, 2008)
• Concerns about negative effects of participation
have not been proven e.g. communities self-correct
(Esquivel et. al. 2006)

17. New sources of authority in healthcare
Patients themselves as experts
“Americans' pursuit of health takes place within a
widening network of both online and offline
sources. Whereas someone may have in the
past called a health professional, their Mom, or
a good friend, they now are also reading blogs,
listening to podcasts, updating their social
network profile, and posting comments. And
many people, once they find health information
online, talk with someone about it offline.”
Susannah Fox, The Social Life of Health Information
Pew Internet Report

18. The Result:
People, globally and of all ages, trust
providers and a “people like me” equally
2008 Edelman Trust Barometer

19. 3. People also putting structured data
online: tracking outcomes

20. 3. Significance to patients: Participatory Research
“As these [life raft] examples show, patient-driven research will
become more and more important, and will provide an example
of the way things will go in the future. As other patient groups
begin generating their own medical data, it will change the
relationships between research professionals, clinicians, and
patients quite dramatically.
Gilles Frydman, President of Association of Online Cancer Resources
PatientsLikeMe ALS Members
organized to track outcomes on an
experimental treatment

21. One company focuses on using these
outcomes
PatientsLikeMe case study
•Started in 2006
•Now over 100,000 members
•Began by building communities for conditions,
now building a broader platform

22. Opportunity

23. Core Platform
SHARE FIND LEARN
Patients sharing detailed Patients find other patients like The information shared creates
health data is what makes them. They discover what a new knowledge about the
our communities unique. options are available for real-world treatments,
This information is the basis treatment and if their experience symptoms, and reality of living
of the PatientsLikeMe with their disease is normal. They with illness. Patients learn about
network and validates each can reach out to others like them their disease and themselves in
individual. for advice and insight. context of the community.

24. How it works

25. Value of PatientsLikeMe:
Some Results from a User Survey
1,323 Users completed the survey
(19% response rate)
• 71% helpful in learning about the symptoms
they are experiencing
• 67% they are getting better care by recording
symptoms over time
• 69% agreed with “I feel more comfortable
asking for information on sensitive topics such
as sex, sexuality, religion, or spirituality ” than
online and offline support groups

26. Using the platform to better understand
off-label prescriptions:
Studied two drugs prescribed off-label
• Amitriptyline
• Modafinil

27. The Amitriptyline Case
• The drug most commonly prescribed
off-label (Radley, et. al. 2006)
• One FDA approved purpose
(depression)
• 14 Amitriptyline clinical trials
recruiting subjects (clinicaltrials.gov)

28. Method
Analyzed site data
• Treatment histories
– Prevalence
– Treatment purpose
• Drug evaluations
– Efficacy
– Side-effects
• At time of analysis 53,926 site members

29. Amitriptyline Dataset
• 1,394 treatment reports for amitriptyline
• 865 currently taking the drug
• 2% of members
• 1,197 evaluations of Amitriptyline
• 5 PatientsLikeMe communities
MS, Parkinson’s, Mood Conditions, ALS, Fibromyalgia
At time of analysis there were 53,926 site members

30. Online version

31. Results: Purposes
Common purposes:
– Insomnia and other sleep problems (27%)
– Pain (17%)
– Depression (9%)
91% for off-label purposes
Of note:
8% of ALS patients report taking the drug
40% of them to treat excess saliva

32. Results: side effects
Most commonly reported side effects:
– Feeling sleepy, groggy, or drowsy (46%)
– Dry mouth (29%)
– Weight gain (22%)
Based on 270 side-effect reports

33. Results: Efficacy of Amitriptyline
Drug rated more effective for off-label
compared to approved purpose:
Purpose Moderate or Major Effect
Off–label indications 52%
Depression 40 %
Based on: 70 reports for purpose of depression
And, 520 reports for off-label purposes

34. Study Conclusions
• Patient platforms offer a unique data source for
understanding utilization and treatment
experience across populations
• Can access more cases than traditional trials
with a low barrier to participation
• This patient reported outcomes from these sites
can provide evidence about:
– Secondary uses of drugs (excess saliva)
– Drugs that are off-patent and therefore unlikely to be
studied systematically

35. The Problem in 1870’s and Now?
"Medical knowledge is at a low ebb among us," said Mr. Bulstrode,
…"I, for my part, hail the advent of Mr. Lydgate. I hope to find
good reason for confiding the new hospital to his management."
"That is all very fine," replied Mr. Standish, who was not fond of
Mr. Bulstrode; "if you like him to try experiments on your hospital
patients, and kill a few people for charity I have no objection.
But I am not going to hand money out of my purse to have
experiments tried on me. I like treatment that has been
tested a little."
"Well, you know, Standish, every dose you take is an
experiment-an experiment, you know," said Mr. Brooke,
nodding towards the lawyer.
George Eliot, Middlemarch 1876

36. Conclusions
Number of challenges for data collection
•Rise of personalized medicine
•Growing concern about the ethics of clinical trials
Need for novel solutions
Patients are motivated to participate and have a
unique perspective
Incorporating the patient voice should be a part
of those solutions

37. Thank You
j.h.frost@vu.nl
VU Amsterdam
KankerNL

38. “To listen well is as powerful a
means of communication and
influence as to talk well.”
John Marshall