Non-adherence of CML patients

Results of the global survey of theCML Advocates Network

Giora SharfCo-founder, CML Advocates NetworkDirector, Israeli CML Patients’ Organization

Confidential & Proprietary. Not For Public Distribution. Do Not Copy.2

What we will cover »

The story so farAdherence

LevelsInfluencers of

Adherence

Demographics & Treatment

Beliefs & Motivation

Strategies for Adherence

CML Advocates Network: global network ofleukemia patient groups

http://www.cmladvocates.net

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

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 guidelinesand 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

Where we are now

• 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

TKIs have revolutio-

nised CML treatment so people can live longer

However, non-

adherence is a key issue in

CML

There is a clear link between

adherence and

survival rates

• 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 long-term 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 2-3 daily doses each month can negatively impact response

Long Term Adherence to Imatinib Alex Bazeos et al, ASH 2009

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

Our research was truly global: 12 languages, 2546 CML patients from 79 countries

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

395Paper

Online

Countries with >30 respondents

Countries with base <30 respondents

We used the validated Morisky Adherence Scale to classify patients into adherence levels

Questions:

Forget medication

Miss for other reason

Stopped because felt worse

Forgot when travelling

Taken yesterday?

Stop when under control

Inconvenience

How often having difficulty to remember

Low: 21 %

Medium: 47 %

High: 33 %

Adherence score classifies patients into

adherence groups:

Adherence levels

USA and Serbia stand out through the proportion missing doses, both accidentally & intentionally

% Missed Accidentally / Due to Circumstance in last year

“Above global average for missed

doses”

Global Average

Global

Average

“Below global average for missed

doses”

Slovenia stands out as the most adherent country via the Morisky scale

Adherence by Market - Proportion Classified as High %

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?

+

N.B. Higher sample size = more likelihood of a sig.

diff.

Venezuela & Australia have the lowest proportion of adherent patients according to the Morisky scale

Adherence by Market - Proportion Classified as High %

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?

_

_

N.B. Higher sample size = more likelihood of a sig.

diff.

29% have missed a dose accidentally in the last month. 11% have intentionally decided to miss a dose.

Missed a dose accidentally in last month %

3 average doses

missed in last month

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, other Cen. & Lat. Am.

+Yes: Ser., USA

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.

Patients in the low adherence group are usually of lower age

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

Old

er

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!)

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?

Current Medication %

Nilotinib

Imatinib

Dasatinib

Other + don’t know

Nilotinib has fewer high adherers than the other two therapies

B3a / base-all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833) - Which medication do you take for your CML currently?

Current Medication vs. Levels of Adherence %

+

Nilotonib

+

Nilotonib

Those with low adherence are more likely to take their medication 2x/day & do so 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?

Low adherers are also aware that the doses they miss most are their evening doses (34%)

How many times take medication % / Av.

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

Forgetting & routine interruption primary reasons for accidental, side effects for intentional non-adherence

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?

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

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

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

Joint responsibility: Adherence is strongly influenced by doctor-patient relationship

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 %

So what can we doto drive adherence?

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.

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

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?

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

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

More information about this study:www.cmladvocates.net/adherence

Giora Sharf

Israeli CML Patients OrganizationCML Advocates Network

giora@cmladvocates.net