"Non-adherence of CML patients - Results of the global survey of the CML Advocates Network", presented by Giora Sharf, Co-founder, CML Advocates Network and Director, Israeli CML Patients’ Organization, for the International CML Foundations' "Virtual Education Program"

1. Non-adherence of CML patients
Results of the global survey of the
CML Advocates Network
Giora Sharf
Co-founder, CML Advocates Network
Director, Israeli CML Patients’ Organization

2. 
What we will cover »
The story so far
Influencers of
Adherence
Demographics &
Treatment
2
Adherence
Levels
Beliefs &
Motivation
Strategies for
Adherence
Confidential & Proprietary. Not For Public Distribution. Do Not Copy.

3. CML Advocates Network:
global network of
leukemia patient groups





Public directory of
Chronic Myeloid Leukemia
groups
“Social media platform” to have
advocates collaborate
Build skills, coordinate
campaigns, build partnerships,
share knowledge
Founded 2007 by 4 advocates
82 patient organisations
in 64 countries
http://www.cmladvocates.net

4. CML has turned from a fatal disease into
a chronic disease in the last 15 years

15 years ago, surviving 5 years had a chance of 50:50

Today, when treated according to guidelines
and high adherence, survival is
close to general population

Side effects are still a problem

Psycho-oncology services often
not offered

The lion is in the cage, but adherence is a serious issue

5. Where we are now
TKIs have
revolutionised CML
treatment
so people
can live
longer
However,
nonadherence
is a key
issue in
CML
There is a
clear link
between
adherence
and
survival
rates
Long Term Adherence to
Imatinib
Alex Bazeos et al, ASH 2009
• The launch of
imatinib, a BCR-ABL
kinase inhibitor,
transformed the
treatment of CML,
and indeed the face of
oncology as a whole
• 2nd generation
products, nilotinib and
dasatinib, are
designed to manage
instances of imatinib
resistance
• Adherence is a
complex and
multifactorial issue,
especially in medical
conditions that require
long-term therapy
such as chronic
phase CML
• A combination of
internal and external
factors may lead to
reduced patient
adherence to longterm therapies
• Both the
HAMMERSMITH
study and the
ADAGIO study
highlighted the
importance of patient
compliance in
regards to achieving
optimal treatment
response
• Missing more than 23 daily doses each
month can negatively
impact response

6. Prior studies demonstrated non-adherence is
key problem in CML – and has clinical impact
(ADAGIO 2008, / Bazeos 2009)
We aimed to replace “gut feeling” by solid data to
better understand the problem:
Understand patient behaviours associated with adherence
And 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

7. Our research was truly global: 12 languages,
2546 CML patients from 79 countries
Global reach
Countries with >30
respondents
Countries with base <30
respondents
Sample: Total of 2546 respondents
Online
2151
Paper
395
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

8. We used the validated Morisky Adherence Scale
to classify patients into adherence levels
Questions:
Forget medication
Miss for other reason
Stopped because felt
worse
Adherence score
classifies patients into
adherence groups:
Low: 21 %
Forgot when travelling
Taken yesterday?
Stop when under control
Medium: 47 %
Inconvenience
How often having
difficulty to remember
High: 33 %

9. Adherence levels

10. USA and Serbia stand out through the
proportion missing doses, both accidentally &
intentionally
Global Average
% Missed on Purpose in last year
“Above global
average for missed
doses”
Russian Federation
USA
Serbia
Argentina
Australia
Israel
India
Mexico
France (Online) Lebanon
Venezuela
UK Poland
Philippines
Italy (Online)
Netherlands Italy (Paper & Pen)
Germany (Paper & Pen)
Finland
Germany (Online)
France (Paper & Pen)
“Below global
average for missed
doses”
Slovenia
Czech Republic
Thailand
% Missed Accidentally / Due to Circumstance in last year
Global
Average

11. Slovenia stands out as the most adherent
country via the Morisky scale
Adherence by Market - Proportion Classified as High %
+
N.B. Higher sample size
= more likelihood of a sig.
diff.
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?

12. Venezuela & Australia have the lowest proportion
of adherent patients according to the Morisky
scale
Adherence by Market - Proportion Classified as High %
N.B. Higher sample size
= more likelihood of a sig.
diff.
_
_
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?

13. 29% have missed a dose accidentally in the last
month. 11% have intentionally decided to miss a dose.
Missed a dose intentionally
in last month %
Missed a dose accidentally in
last month %
+ Yes: Ser.,
USA, other
Cen. & Lat.
Am.
3
average
doses
missed in
last
month
+Yes:
Ser.,
USA
8%
missed both
accidently
and on
purpose in
the 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 accidental ly 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 dos e? C4b / n=2258 - In the
last year, have you decided to miss a dose?

14. 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) %
+ Neth., Slov.,
Thai., 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.

15. Patients in the low adherence group
are usually of lower age
Age / Gender %
Total adherence
Low
Medium
High
M, H
Younger
-
Male /
H
-
H
Female /
H
-
Female /
Older
-
Male /
L
L, M
L
L
Male /
Female /
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?

16. Imatinib seems to be linked with higher adherence,
Nilotinib is more prevalent in the low adherence group
(based on Morisky Scale, so different motivations for non-adherence regarded!)
Current Medication %
Imatinib
Nilotinib
Dasatinib
Other + don’t know
B3a / base-all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833) - Which medication do you take for your CML currently? B3a/B6 / base=all respondents (n=2546) - Which
medication do you take for your CML currently? What CML treatments, if any, did you have before you began to take the one you are currently taking?

17. Nilotinib has fewer high adherers than the
other two therapies
Current Medication vs. Levels of Adherence %
+
Nilotonib
+
Nilotonib
B3a / base-all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833) - Which medication do you take for your CML currently?

18. Those with low adherence are more likely to take
their medication 2x/day & do so in the evening
How many times take medication % / Av.
Av.
1.3
Av. M, Av. 
1.4
H 1.3 H
M, H
Time of day that take medication %
Av.
1.3
H H
L
L, M
L,
M
H, M
H
Low adherers
are also aware
that the doses
they miss most
are their
evening doses
(34%)
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?

19. Forgetting & routine interruption primary reasons
for accidental, side effects for intentional nonadherence
Reason for missing accidentally % (n=1283)
Reason for deciding to miss % (n=491)
Whilst accidental missing is more linked to memory,
purposeful missing of doses is more related to physical symptoms
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?

20. Low adherence group worries more about
QOL and long term side effects, and is not
clear about consequences
Attitudes towards CML treatment by adherence groups (top 3 box%)
My health depends on my CML medication
H, M

I have been told I need to take every dose of my
CML treatment or the treatment may not work
L

I worry if I miss a dose of my CML medication
H, M
I worry about the long term effects of my
CML medication
H
Having to take my CML medication
worries me
H
H
My CML medication impacts my work life
H
My CML medication impacts my social life
H
My CML medication disrupts my life
It is ok to miss a few doses of my CML medication
every now and then
H
I find it difficult to swallow my CML medication
H, M
H, M
H, M
H, M
H, M
H, M
H, M
I find it difficult to open / close the CML medication
packages
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)

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

22. So what can we do
to drive adherence?

23. What can patients groups do?

Improve communication on adherence
between patients and physicians

Raise the profile of adherence issues in
the community - patient information,
meetings, doctors, relatives, industry!

Support with routines, provide reminders.

24. Reminders from family members & pill
dispensers are primary tools used, followed
by electronic reminders
Tool Usage (%)
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

25. In fact, those with better adherence are
particularly tied to their routines
Helpfulness of routines 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?

26. Conclusion

Patients do not want to be patients.
Daily drug taking reminds them that they are sick.

"This is cancer! Of course my patient is taking his
medicine" is mostly a misled assumption.

There are “at risk” groups like younger patients, longer
time on treatment, taking the drug twice a day that need
special attention.

There are intentional and non-intentional mechanisms of
non-adherence. Physicians and patient groups need to
address them jointly.

More information on this study:
www.cmladvocates.net/adherence

27. 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

28. More information about this study:
www.cmladvocates.net/adherence
Giora Sharf
Israeli CML Patients Organization
CML Advocates Network
giora@cmladvocates.net