1. Patient Directed Research Jane F. Apperley Imperial College London, United Kingdom

2. Common forms of patient involvement in research Giving samples for research Consenting for data and results to be used in retrospective (looking back) studies Being in a clinical trial Being a member of a specialist disease group Participating in the design of clinical trials

3. Features of these forms of research Desire is to gain information to add to an evidence-base Hypothesis (idea) comes from health-care professional Collection of data either from events that have already occurred (retrospective) or are going to occur (entry into clinical trials) Requirement for a certain rigor in design and conduct so that any presentation and/or manuscript will be well reviewed by professional colleagues and accepted for wider dissemination – usually at a medical meeting or in a medical journal

4. But we are in 2015!

5. Confidential & Proprietary. Not For Public Distribution. Do Not Copy. 5 CML Patient Adherence Leukemia Patients Advocates Foundation February 2013

6. Confidential & Proprietary. Not For Public Distribution. Do Not Copy. 6 The research had truly global reach; an impressive number of respondents took part Sample: Total of 2546 respondents Global reach Methodology: Online and paper surveys Online - Recruited by patient associations via online forums & other methods Paper & Pen (France, Germany, Italy) – Recruited by physicians at consultations Chronic Myeloid Leukaemia patients over 18 years old, currently taking oral medication for CML Fieldwork – 22 nd September 2012 – 30 th January 2013 2151 395 Paper Online Countries with >30 respondents Countries with base <30 respondents

7. Confidential & Proprietary. Not For Public Distribution. Do Not Copy. 7 About ¾ of respondents believe they take their CML medication exactly as prescribed 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., Thai., It. (paper) However, 19% of those who stated ‘I always take my medicine exactly as prescribed’ had missed a dose accidently in the last month. This indicates that there may be a gap between perception & reality for some.

8. Confidential & Proprietary. Not For Public Distribution. Do Not Copy. 8 One fifth of respondents qualify as having “low” adherence Global adherence % 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?

9. Confidential & Proprietary. Not For Public Distribution. Do Not Copy. 9 Forgetting & routine interruption are primary reasons for missing accidentally 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) Side effects aiming to reduce (NET): Gastro (79%) Dermatologica l (17%) Mental(21%) Whilst accidental missing is more linked to memory, purposeful missing of doses is more related to physical symptoms

10. Low adherence Is usually deliberate Tends to be younger patients Linked with Longer duration of disease Less formal education Having to pay for medication Travelling further to see physician and collect medication Perception that treatment affects quality of life Less understanding of the consequences of missing drug Perceive their physicians to be less approachable Nilotinib low adherence linked with concern of current/future side effects

11. Confidential & Proprietary. Not For Public Distribution. Do Not Copy. 11 Tools Used (E2) - % Use Already (only sig diff shown) (Base = nilotinib users n=554, imatinib/dasatinib users n=1887) Attitudes to Medication (C8) - % (only sig diff shown) (Base = nilotinib users n=554, imatinib/dasatinib users n=1887) Nilotinib users are more likely to worry about the long term effects & believe that the meds. disrupt their life NilotinibImatinib / Dasatinib E-reminders via mobiles (SMS/alarms) 4318 Alarm clock3614 Reminders from dr.s or nurses at apps 710 Smart phone / mobile applications 138 Phone call reminders75      NilotinibImatinib/Dasatinib I worry about the long term effects of my CML medication 6051 My CML medication disrupts my life 2521   Nilotinib users are also more likely to be using certain tools to support their more frequent dosing (2x a day).

12. Features of this forms of research Global coverage Identifies country and cultural differences, and the effect of different healthcare systems Large numbers of respondents make the research very powerful We don’t know why individuals respond to these surveys. Are adherent or non-adherent patients more or less likely to respond? Average age of respondents was 50, average age of disease is 60 From the perspective of a scientific journal the research can be criticised for the possibility of bias

13. Topics that lend themselves to patient directed research Compliance Type and frequency of side effects, particularly long-term side-effects Effects on fertility Outcome of pregnancy Outcome of stopping treatment

14. Possible Solutions to Perceived Problems Use in a situation where bias is less likely or can be overcome with very large numbers of patients Work with the physician to ensure coverage of all eligible patients eg. if an individual reports the outcome of stopping treatment, approach the physician to see if they had stopped the drug in other patients, and try and encourage these individuals to report also Continue to develop the processes and dialogue with scientific journals: without a peer reviewed output there is little chance of funding CML Advocates will launch a pregnancy survey in 2016

15. In the meantime Ask your physician if you can take part in research Ask your physician if your data is being sent to a population based registry Volunteer your data and/or your samples Consider clinical trial participation Get involved in groups that want to do research, but remember that it has to be done a scientifically sound manner – you don’t want to add to the wealth of poor information It’s your disease – own it and help others to do so

16. Speakers Mandy Sale Staff at W12 Conference Centre Attendees