Patient participation in clinical research.

Melanoma Bridge meetingNaples 3rd Dec 2014

Melanoma Patient Network Europe

Bettina Ryll, MD/PhD

www.melanomapatientnetworkeu.org

potential conflict of interests

At this time,

Advisory function to the following Pharma: Amgen, GSK, Merck-Serono, Novartis, Roche.All honoraries received are handled by the Anticancer Fund, Belgium, on MPNE’s behalf and used for the work of MPNE.

MPNE projects are funded by grants/ sponsorships from the pharmaceutical industry: funding is always balanced and does not entail any rights to influence the concept/ faculty/ program. (Amgen, BMS, GSK, MSD, Merck-Serono, Novartis, Roche)

Melanoma Patient Network Europe

12/4/2014www.melanomapatientnetworkEU.org

WMA Helsinki DeclarationEthical Principles for Medical Research involving Human Subjects- 1964, last amendment 2013

3. The declaration of Geneva of the WMA binds the physicians with the words ‘The health of my patient will be my first consideration’ and the International Code of Medical Ethics declares that, ‘A physician shall act in the patient’s best interest when providing medical care’.

…

8. While the primary purpose of medical research is to generate new knowledge, this goal can never take precedence over the rights and interests of individual research subjects.

….

26. …The potential subject must be informed of the right to refuse to participate in the study or to withdraw consent to participate at any time without reprisal. ….

Show me the evidence-

• unethical trials violating equipoise, inappropriate use of blinding and placebos

• confirming rather than learning trials • ‘Pharmageddon’- ever-decreasing ROI in Pharma• increasing drug prices- resulting in access problems

for our patients

… all in the name of evidence-based medicine.

“Avoidable waste in the production and reporting of research evidence”Iain Chalmers, Paul Glasziou, The Lancet, 15 June 2009, doi:10.1016/S0140-6736(09)60329-9

Over 30% of trial interventions not sufficiently described

Over 50% of planned study outcomes not reported

Most new research not interpreted in the context of systematic assessment of other relevant evidence

Unbiased and usable report?

85% research waste = over $85 billion / year

Low priority questions addressed

Important outcomes not assessed

Clinicians and patients not involved in setting research agendas

Questions relevant

to clinicians & patients?

Over 50% studies designed without reference to systematic reviews of existing evidence

Over 50% of studies fail to take adequate steps to reduce biases, e.g. unconcealed treatment allocation

Appropriate design and methods?

Over 50% of studies never published in full

Biased under-reporting of studies with disappointing results

Accessible full

publication?

1 2 3 4

slide courtesy J. Geissler

Only patients know what patients know- 1

Detecting Myeloma, ways to shortening an often painful and tedious patient odyssey: results from an international

survey. Myeloma Euronet (2009). 314 physicians & nurses, 260 patients & carers, 43 countries

slide courtesy J. Geissler

Only patients know what patients know- 2

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.

original slide courtesy J. Geissler

Adherence Study by the CML advocate network- MEMS®, Morisky Adherence Scale

2546 CML patientsin 79 countries

DATA NOT OPINIONS

• Everyone is biased.

• Patients’ preferences are as diverse as the preferences of any other stakeholder group-there is no single medical KOL voice either.

• We need scientific tools to account for bias and diversity.

trial management, e.g. consent, patient

information leaflets, trial adherence

patient recruitmente.g. providing information on clinical trials, advertising trials

clinical trial design

Patient involvement in clinical trial design

12/4/2014

clinical question/ problem

current patient involvement

impact on patients

doing the right thing doing things right

http://www.informed-scientist.org/presentation/the-role-of-patient-groups-in-the-clinical-trial-process B. RYLL

Current scenario:

Post-licensing, treatment population grows rapidly; treatment experience does not contribute to evidence generation

Adaptive Licensing:

after initial license, number of treated patients grows more slowly, due to restrictions; patient experience is captured to contribute to real-world information

Eichler HG et al. Clin Pharmacol Ther. 2012

11

Innovative Drug Licensing Models-e.g. Adaptive Licensing

original slide courtesy F. Pignatti

Melanoma patients need

• ethical trials on the basis of Helsinki respecting patients’ real and not perceived or projected interests.

• a sustainable drug development system ensuring innovative, effective and safe enough drugs at an affordable price.

• sophisticated models for trial design- e.g. Bayesian designs-and innovative drug development models- like Adaptive Licensing, break-through designation- to account for the specific condition of high unmet need and highly promising new therapeutical developments.

Because evidence-based medicine is the tool, not the goal.

Conference documentation- https://www.youtube.com/watch?v=wilTXvFN2NU

MPNE 2014

MPNEwww.melanomapatientnetworkeu.orgWe are also on facebook, linkedin, twitter and youtube

Contact Bettina mpneurope@gmail.com

Next MPNE conference‘The risk of not taking risks in Melanoma’

24-26th April 2015, Brussels

Thank you

for your attention