NON-ADHERENCE IN CHRONIC MYELOID LEUKEMIA: RESULTS OF A GLOBAL SURVEY OF 2546 CML PATIENTS IN 79 COUNTRIES: Giora Sharf, Verena Hoffmann, Felice Bombaci, Mina Daban, Fabio Efficace, Joëlle Guilhot, Jana Pelouchová, Euzebiusz J. Dziwinski, Jan de Jong , Anthony Gavin, Jan Geissler EHA Abstract S1104 - Presented in the session "08. CML - Clinical" by Giora Sharf, CML Advocates Network, at the European Hematology Association (EHA) Congress 18 in Stockholm, 16/6/2013

1. 1
NON-ADHERENCE IN CHRONIC MYELOID
LEUKEMIA: RESULTS OF A GLOBAL SURVEY
OF 2546 CML PATIENTS IN 79 COUNTRIES
EHA Abstract S1104 - Stockholm, 16/6/2013
Giora Sharf, Verena Hoffmann, Felice Bombaci, Mina Daban, Fabio
Efficace, Joëlle Guilhot, Jana Pelouchová, Euzebiusz J. Dziwinski, Jan de
Jong , Anthony Gavin, Jan Geissler

2. CML Advocates Network:
the global network of
leukemia patient groups
http://www.cmladvocates.net
Connecting 77 organisations from 61 countries
Key facts
• Public directory of CML groups
• “Social media platform” to have
CML patient advocates collaborate
• Build skills, coordinate campaigns, build partnerships,
share knowledge
Founded 2007 by 4 patient advocates

3. Prior studies demonstrated non-adherence is key
problem in CML (ADAGIO 2008, Hammersmith) –
and has clear clinical impact (Bazeos 2009)
Objectives of our patient-driven study:
Understand patient behaviours associated with adherence
Help identify the „true‟ issues behind non-adherence
Explore cultural influence and difference on adherence
Support development of physician and patient tools to improve
adherence and improve patient outcomes

4. Truly global research in 12 languages:
2546 CML patients from 79 countries participated
Sample: Total of 2546 respondentsGlobal reach
Methodology
• Online - Recruited by patient associations online & via other methods
• Paper & Pen (France, Germany, Italy) – Recruited by physicians at consultations
• CML patients over 18 years old, currently taking oral medication for CML
• Fieldwork – Started on CML World Day, 22/9 2012 – 30th January 2013
2151
395
Paper
Online
Countries with >30
respondents
Countries with base <30
respondents

5. We also used the validated Morisky Adherence Scale
to classify patients into adherence levels
Questions:
Forget medication
Miss for other reason
Stopped because felt
worse
Forget when travelling
Take yesterday?
Stop when under
control
Inconvenience
How often difficulty
remembering
Low: 21 %
Medium: 47 %
High: 33 %
Adherence score
classifies patients into
adherence groups:
F1/ base = all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833) - Please answer „yes‟ or „no‟ to each question based on your personal experience with your
CML medication. F2/ base = all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833) - How often do you have difficulty remembering to take all your
medications?
Use of the ©MMAS is protected by US copyright laws. Permission for use is required. A license agreement is available from: Donald E. Morisky, ScD, ScM, MSPH, Professor,
Department of Community Health Sciences, UCLA School of Public Health, 650 Charles E. Young Drive South, Los Angeles, CA 90095-1772.

6. 6
The results presented are initial
descriptive findings.
In-depth analysis will follow,
including specific countries.

7. 29% have missed a dose accidentally in the last month.
11% have intentionally decided to miss a dose.
29
68
2
Yes
No
Don't Know
Missed a dose accidentally in
last month %
3
average
doses
missed in
last
month
11
89
Yes
No
Missed a dose intentionally
in last month %
C2a / base=all respondents (n=2546) - Patients sometimes are not able to take their medication as prescribed. In the last month, have you missed a dose accidentally or due to
circumstances that were outside of your control? C2b / n=746 How many doses did you miss in the last month? C2c / base=all respondents (n=2546) – In the last year, have you missed a
dose accidentally or due to circumstances that were outside of your control? C2b & C2cc / base=all respondents (n=2546) - How many doses did you miss in the last month/year? C4a /
base=all respondents (n=2546) - Patients sometimes make a conscious decision to miss a dose of medication. In the last month, have you decided to miss a dose? C4b / n=2258 - In the
last year, have you decided to miss a dose?
8%
missed both
accidently
and on
purpose in
the last
month
+ Yes:
Ser., USA, ot
her Cen. &
Lat. Am.
+Yes:
Ser.,
USA

8. 11 3 21%
74% - always
stick to therapy
as prescribed
1 - Rarely take exactly as prescribed 2 3 4 5 - Always take exactly as prescribed
74% believe they take their CML medication exactly as
prescribed, but 19% of them missed a dose last month
Self rated adherence (rated 1-5) %
C1 / base=all respondents (n=2546) - In general, to what extent do you think you are able to stick to your CML therapy schedules and dosage, as prescribed by your CML doctor? C1 / C2a
/ base (n=1886) - Patients sometimes are not able to take their medication as prescribed. In the last month, have you missed a dose accidentally or due to circumstances that were outside
of your control?
+
Neth., Slov., Th
ai., It. (paper)
BUT: 19% of those who claim to always take
medicine as prescribed, had in fact missed a
dose accidently in the last month.
 Gap between perception & reality.

9. Serbia
USA
Lebanon
Venezuela
Poland
Russian Federation
Australia
France (Online)
Argentina
UK
France (Paper & Pen)
Philippines
Czech Republic
India
Italy (Online)
Italy (Paper & Pen)
Finland
Israel
Netherlands
Thailand
Mexico
Slovenia
Germany (Online)
Germany (Paper & Pen)
5
10
15
20
25
30
35
40
45
5 15 25 35 45 55 65 75 85
USA and Serbia stand out through the proportion
missing doses, both accidentally & intentionally
%MissedonPurposeinlastyear
% Missed Accidentally / Due to Circumstance in last year
“Above global
average for missed
doses”
Global Average
Global Average
“Below global
average for missed
doses”
C2a / base=all respondents (n=2546) - Patients sometimes are not able to take their medication as prescribed. In the last month, have you missed a dose accidentally or due to
circumstances that were outside of your control? C2c / base=all respondents (n=2546) – In the last year, have you missed a dose accidentally or due to circumstances that were outside
of your control? C4a / base=all respondents (n=2546) - Patients sometimes make a conscious decision to miss a dose of medication. In the last month, have you decided to miss a dose?
C4b / n=2258 - In the last year, have you decided to miss a dose?

10. Forgetting & routine interruption are primary reasons
for accidental, (gastro) SE for intentional non-adherence
1
1
4
6
7
9
15
17
27
41
Dosing schedule complicated
Couldn't swallow
Reminder failed
Medication not ready at
pharmacy
Ran out of medication
Fell asleep
Too ill
Travelling
Interrupted routine
Forgot
Reason for missing accidentally % (n=1283)
C2d / n=1283 - Which circumstances led to a missed dose of your medication? C5 / n=491 - Why did you decide to miss a dose of your medication? C6 / n=126 - Which side effect(s) were
you hoping to avoid by intentionally missing one or more doses of your medication?
0
1
2
4
4
7
9
9
10
10
11
26
35
Friend/partner said could miss
To save money
Feeling better
Didn't want to be reminded
Interfered with work
CML under control
Dr said could miss
Feeling down
Interfered with travel
Wanted to socialise
Attending special occasion
Reduce side effects
Not feeling well
Reason for deciding to miss % (n=491)
Side
effects
aiming to
reduce:
Gastro
(79%)
Dermatolog
ical (17%)
Mental
(21%)
Whilst accidental missing is more linked to memory,
purposeful missing of doses is more related to physical symptoms

11. 13 13 12 13
1 2 1 1
3
6
2
2
13
23
13
7
69
56
71 76
Total Low Medium High
Routine helps
greatly
Routine helps
moderately
Routine helps
little
Routine does
not help
I do not have a
routine
In fact, those with better adherence are particularly
tied to their routines
Helpfulness of routine amongst adherence groups %
+Israel, Leb., Mex.,
USA, Ger.
(online), Italy
(paper)
L
L
E1 base = all respondents (n=2546), Low (n=528), Medium (n=1185), High (n=833) In order to remember to take their medication, patients sometimes try to follow a routine. Does having a
daily routine help you remember to take your medication?

12. Patients in the low adherence group
are usually of lower age
14
12
18
17
20
18
21
20
15
20
10
14
14
12
19
17
19
19
11
7
18
16
28
20
Male / 18-40
Female / 18-40
Male / 41-55
Female / 41-55
Male / 56+
Female / 56+
Age / Gender %
A1 / base=all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833) – How old are you? A2 / base=all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833)
– What is your gender?
Total adherence HighMediumLow
M, H
 H H
H
L
L
L, M
L
YoungerOlder

13. Imatinib seems to be linked with higher
adherence, Nilotinib more prevalent in low
adherence group
(on Morisky Scale, so all motivations for non-adherence regarded!)
B3a / base-all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833) - Which medication do you take for your CML currently?
19
27
21
46
48
46
36
25
33
Imatinib Nilotinib Dasatinib
High
Medium
Low
Current medication vs. levels of adherence %
+
Nilotinib
+
Nilotinib

14. Low adherence group more likely to take their
medication 2x day or in the evening
Time of day that take medication %
B4a / base=all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833) - How many times a day do you take your CML medication? B4b / base=all respondents (n=2546) Low
(n=528), Medium (n=1185), High (n=833) - When during the day do you usually take your CML medication?
34
19
51
41
21
45
49
21
40
40
20
46
Evening
Midday
Morning
Total
Low
Medium
High
Low adherers
are also aware
that the doses
they miss most
are their evening
doses (34%)
How many times take medication % / Av.
69
61
68
76
27
35
29
21
Total Low Medium High
4x a day
3x a day
2x a day
1x a day
Av.
1.3
Av.
1.3
Av.
1.4
Av.
1.3
M,
H

H
M, H H
L, M
L
L, M
H, M
H
H

15. My health depends on my CML medication
I have been told I need to take every dose of
my CML treatment or the treatment may not
work
I worry if I miss a dose of my CML medication
I worry about the long term effects of my CML
medication
Having to take my CML medication worries me
My CML medication impacts my work life
My CML medication impacts my social life
My CML medication disrupts my life
It is ok to miss a few doses of my CML
medication every now and then
I find it difficult to swallow my CML medication
I find it difficult to open / close the CML
medication packages
Low adherence group worries more about QoL and long
term side effects, and is not clear about consequences
0 10 20 30 40 50 60 70 80 90 100
Low
Medium
High
Attitudes towards CML treatment by adherence groups (top 3 box%)
C8 / base=all respondents (n=2546). Low (n=528), Medium (n=1185), High (n=833) When thinking about your CML medication, please indicate the extent to which you agree with each of
the following statements? (Please indicate for each item below on a scale of 1-7 where 1=strongly disagree and 7=strongly agree)
H, M
H, M
H, M
H, M
H, M
H, M
H, M
H
H, M

L
H, M
H
H
H
H
H

16. 16
Importance of relationship
of doctors and patients

17. Adherence is strongly influenced on relationship of
CML patient with physician
High adherence group is more likely to discuss missing a dose with their physicians
High adherence group is more satisfied with info received from HCPs
& HCPs is perceived to be approachable
Accidentally HIGH LOW
„Yes always“ 83 % 47 %
Intentionally HIGH LOW
„Yes always“ 85 % 48 %
Info received HIGH LOW
„Very satisfied“ 69 % 45 %
„Not satisfied at all“ /
„Somewhat dissatisfied“
4 % 16 %
HCP is approachable HIGH LOW
„Very approachable“ 73 % 53 %
„Not very approachable“ 7 % 14 %

18. 18
Tools to drive Adherence

19. Reminders from family members & pill dispensers are
primary tools used, followed by electronic reminders
Tool Usage (%)
44
43
54
67
75
60
79
78
83
9
14
19
10
10
26
12
13
9
43
40
24
19
10
9
5
5
3
Reminders from fam.members
Med. box/pill dispenser
E-reminders via mobiles (SMS/alarms)
Alarm clock
Reminders from dr.s or nurses at apps
Smart phone / mobile applications
Phone call reminders
Refrigerator magnet reminders
Email reminders
I would not use I would use if available I already use
Possible future niche in mobile
applications for over ¼ of patients
E2 base = all respondents (n=2546) Below is a list of tools that could help you to remember to take your CML medication. For each item, please indicate whether you already use such a
tool, or if you would use the tool if it were available
+ Under 30 yrs
+ Under 30 yrs
+ Under 30 yrs
+ Under 30 yrs
+ Under 30 yrs
+ Under 30 yrs
+ Under 30 yrs

20. 20
Conclusions &
Recommendations

21. Conclusions
Haematologists…
• should not take the patients adherence assessment for granted
• have a central role in driving adherence – what tools would help?
• should discuss impact of medication on patients lives more
(side effects & quality of life) to drive adherence
• should highlight impact of routines in taking the drug
Particular attention paid to more “at adherence risk” groups:
• Younger patients
• Longer time on treatment
• Twice daily regimen, strong side effects
There is future potential for tools to support adherence…
Priority is on change of mindset of low adherers…
…in partnership with us!

22. 22
Thank you!
To the CML patients in 79 countries that participated.
To the CML patient organisations supporting the survey.
The Workgroup:
Giora Sharf, Verena Hoffmann, Felice
Bombaci, Mina Daban, Fabio Efficace,
Joëlle Guilhot, Jana Pelouchová,
Euzebiusz J. Dziwinski, Jan de Jong,
Anthony Gavin, Jan Geissler
Our Partners:
German CML Study Group – GIMEMA Italy – French FI LMC Group

23. 23
Disclosures
Giora Sharf:
• Research support from
Ariad, BMS, Novartis, Pfizer
• Patient Advisor of Ariad, Novartis, BMS, Pfizer