What is Stratified Medicine to a Patient?

Janette Rawlinson

Lung Cancer Research Stratified Medicine Educational Event

22nd June 2015 Winterbourne House & Garden, Birmingham

What is Stratified Medicine?

• Google provided me lots of waffle – enough to cure insomnia or at least confirm my inadequacies!

• What does this mean in English to a patient?

• How would I know?

Educational Background/context • I speak and understand different languages –

– English including Black Country/Brummie!– French – German – Spanish – Italian – Latin

I am familiar with – Some medical/health terminology – Business and commercial terminology– Economic development terminology– I undertake independent evaluations of various projects so understand

research methodologies and translational aspects of this to change practice

Educational Background/context • Despite biology, chemistry and mathematics ‘O’ levels amongst my 11 ‘O’ levels and 4 ‘A’

levels, science was not my forte although genetics, human biology and behaviour fascinated me

• Reading research papers, abstracts, websites, and attending conferences or educational events I realise that I need to be expert in – Medical science -imaging and medical illustration – clinical practice -radiotherapy – genetics - pathology– biology - applied research – pharmacology - surgery– Probability, statistics and analytics - ethics – UK healthcare organisational awareness – clinical commissioning - Governance and accountability

Context • Autumn 2006 appointed by Secretary of State as Non-

Executive Director of Sandwell Primary Care Trust• Spring 2007 appointed Chair of Sandwell Community

Healthcare Services – led Transforming Community Services agenda

• Fairly typical NHS patient/consumer/family experience• Excellent (Dad) versus Poor (sister) • Uneventful (no broken bones, no kids, tonsillectomy age 4,

childhood onset allergies/asthma, suspected collapsed lung age 12, hospitalised with asthma age 16, chest infections, treated with immunotherapy for allergies in 1970s and ‘80s.

Some definitions – where to begin? ‘Stratified medicines are set to transform healthcare in the next wave of pharmaceutical innovation.’

‘The future is not far away. We are already seeing the first wave of these stratified medicines come into the NHS, mainly to treat cancer but therapies in other areas such as neuroscience are also being developed’

‘Stratified medicines enable us to target treatments specifically to patient subpopulations identifying those with the greatest chance of benefit and the lowest risk of suffering adverse events. Called personalised medicine or healthcare in the US, it is better known as stratified medicine in the UK to avoid confusion with individualised healthcare.”

More definitions (2) • ‘It is not about creating medicines unique to a patient, but rather the

ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment.‘

• ‘Preventive or therapeutic interventions can then be concentrated on those who will benefit, sparing expenses and side effects for those who will not’

• ‘As our insight into human biology in health and disease advances, we come to understand on the one hand, the heterogeneity of disease conditions and on the other hand, heterogeneity amongst human population in response to medicine based on their physiological makeup which can be defined at the pharmacological level. ‘

More definitions (3)

• ‘Many pharmaceutical companies are embracing a stratified approach in medicine development, and we predict that analysts will see an increasing proportion of stratification emerging through the pipeline. This is made possible by the advancement of technology and the ability to build in predictive and stratifying biomarkers, as well as improved molecular understanding of disease pathways. ‘

• ‘Put simply, whether patients respond to a particular treatment may depend in part on the subtype of disease that they have, and therefore whether the target in the disease pathway that the medicine was designed to attack is relevant to the disease subtype or their response to treatment as in example above, or their propensity to an adverse reaction. ‘

?????????? Remind me - which patient did you want me to ask? Professor Stephen Hawking?

What on earth does this mean? • Assumptions that patients understand this terminology!• Patients are not stupid - however they need information in

language and formats they understand• Recently participated in considering a European standard approach

for lay summaries in research – incredible viewpoints in the room –patronising and presumptive – plain language does not mean ‘Sun reader’! (oxymoron)

• Some excellent contributions by Pharma health literacy specialists – but apart from myself and founder/president of Terence Higgins Trust, all were researchers, academics or professional patient/public representatives or US pharma reps!

• Vital to have ‘lay’ people in the room, discussions or design if that’s the target audience!

Patients • Until they’ve been touched by cancer, many people are unaware that

cancer is not something alien but caused by our own cells mutating• Most do not appreciate there are over 200 types of cancer• Immediate reaction is that, for most people, the first thought is of

dying as illustrated by Macmillan and other charity ads• Many clinicians are nihilistic especially about lung cancer• Many choose not to find out information about their condition –

leaving it to ‘chance’, ‘God’s will’, ‘we all have to go of something’, ‘well, she smoked, you know’… etc. etc.

• Family members and friends may well start to research or suggest things that can ‘cure’

• Many well meaning people will raise expectations due to media stories• Stigma and myth abound!

Patients/consumers • Generally patients trust those treating them to offer them access to the

best treatment options, diagnostic tools and expertise especially if cancer is a ‘new’ experience for them

• Like cancer cells themselves, patients are different• Some way into their journey, they may become curious, get more involved,

start to learn about their condition and heaven forbid, want to change things or contribute to new ideas especially if they want things to improve

• This may appear threatening to some clinicians• This may go against their culture, learned behaviour or expectations• They may find a ‘voice’, ability to influence, participate, give something

back, help others• Equally they may be relatively passive and not question anything nor want

to learn anything about their condition

Translation difficulties • Many patients unfamiliar with an MDT approach to healthcare never mind a

collaborative/partnership approach to science to stratify medicine for research• Many patients too ill to understand these concepts at the time of diagnosis and early

treatment• Many family members want anything tried that offers chance of prolonging life (even if

unproven or untested)• Some have viewpoints informed by poor science, sensational journalism, unreliable web

sources or celebrity endorsement with little evidence• Patients want access to the best treatments at no cost in line with NHS policy, have little

understanding of how services are commissioned/paid for or organised• Some patients willing to travel anywhere in the country (or overseas if well enough) to

access new treatments if they offer hope even if unsuitable for their specific cancer• Most unfamiliar with the science behind stratified medicine• Many willing to take part in research• Most unaware how healthcare and especially cancer care is organised in the UK

accepting the branding ‘National Health Service’ at face value.

Patients and research involvement • Stratification is not a term recognised with regard to treatment from a GP

• One size fits all – ‘go away and try this treatment and come back if not working’

• I visited Birmingham CRUK centre many years ago to raise awareness around breast cancer for a women’s group and learnt of treatment stratification in breast cancer with Professor Lawrence Young and thought it sounded amazing but a long way off – sci-fi?

• Many people associate research with ‘being a guinea pig for untested treatments’

• Many are curious and want to help either themselves or others

• Many have different experiences of research

Let’s look at research via NCPES

• National Cancer Patient Experience Survey 2012 – 2014 • Annual postal survey commissioned by NHS England• Issued to all adult patients treated Sept-Nov• 70 detailed questions, 70,141 responses in 2014 = 64%• Consumer pressure introduced 3 questions about

research • Analyses by cancer type, Trust, CCG and network with

detailed demographics; age, gender, deprivation, sexuality, ethnicity

Research questions2012• Since your diagnosis, has anyone discussed with you whether you

would like to take part in cancer research? Yes 33% 35%LC• If yes, were you glad to have been asked? Yes 95%• If no, would you like to have been asked? Yes 53%

2013-14 – lung cancer statistics• Have you seen information (e.g leaflets, posters, information,

screens) about cancer research in your hospital?88% 2013 & 2014• Since your diagnosis, has anyone discussed with you whether you

would like to take part in cancer research? 31% 2013 30% 2014• If so, did you then go onto take part in research?62%2013 58% 2014

Responses show: It’s OK to Ask!

• 1/3 cancer patients have a discussion about research

• 86% saw information

• 2/3 of those go onto take part in research

• 95% of those asked are glad to be asked

• 53% of those not asked would be glad to be asked

• Taking part in research is associated with better experience of care

• Significant and persistent variations by cancer, age, network and Trust

Consumer satisfaction• Involvement in research = better patient experience

• In 2013, 87.2% patients did not have a discussion rated care as ‘excellent’ or ‘very good’

• 90.2% had a discussion but did not participate rated care as ‘excellent’ or ‘very good’

• 91.9% had discussion and participated rated care as ‘excellent’ or ‘very good’

• 12.8% who did not have a discussion rated care as ‘less than excellent or very good’

• 9.8% who had discussion but did not go onto participate rated care as ‘less than excellent or very good’

• 8.1% who had discussion and participated rated care as ‘less than excellent or very good’

Meanwhile, my involvement deepens

• Oct 2012 Appointed as Independent Committee Member to Sandwell and West Birmingham Clinical Commissioning Group

• Oct 2012 Invited to RCLCF national conference in Bham as fundraiser. Attended workshop with patients/carers.

• Met Lyn Barrington –CNS, never smoker – diagnosed stage 4 –less than a year to live – campaigning to raise awareness and funds for research.

• Received ad from RCLCF for a new participation opportunity

Experience and Action ... • Less than satisfactory A&E pathway, delays in diagnostics, misdiagnosis, poor communication,

eventually picked up by CT surgeon, lobectomy day 62 with diagnosis almost 1 month later – BAC, T2, N0, treatment = vigilance

• Swam to regain fitness and raise money for RCLCF in memory of friend who died suddenly from LC mets to bones, liver, spine and brain within 3 days of diagnosis after 10 days in hospital and 6 months of unnecessary pain (bad shoulder diagnosis with ibuprofen then community physio as treatment!)

• Online research on cancer charity websites patients forums revealed his was not an isolated case. Shocked to learn how little research was being done into lung cancer due to stigma/blame – less than 5% of all cancer research funding spent on this despite so many deaths – a huge disservice to all but especially to never or former smokers!

• Respiratory consultant and patient advocate and CNS Lyn Barrington suggested my experiences could be put to better use.

• What could I do to change things? I consider myself fortunate.. anger at injustice of research situation can be useful energy if directed wisely!

Entering a new arena• Applied to NCRI Clinical Studies Group as consumer member to help research from consumer perspective.

Appointed Oct 2013. Induction training for NCRI with Macmillan

• NCRI conference Nov 2013 – brain overwhelm! A long time since biology ‘O’ level!

• Welcomed into ‘cancer research community’ – very supportive

• Undertook report of NCRI CSG consumer contribution– abstract/posters accepted by NCRI and Involve conferences Nov 2014

• Attended science training (Elaine Vickers), ICPV VOICE training (Barts Cancer Institute/Queen Mary University) Sept 2014, invited to help IBC event Dec 2014 Bham cancer Centre

• Appointed to NIHR Health Service and Delivery board Aug 2014

• Panel member assessing all CSG annual reports 2014

• Contacted by CRUK re SMP governance board opportunity – appointed Jan 2015

• Survey work on use of mentors within NCRI CSGs 2015

Learning

• NCRI Conference 2013 and 2014 • NCIN Conference 2014 and 2015• BTOG Conference 2014 and 2015• Brain Mets day 2014• Britain Against Cancer Conference 2014• Involve Conference 2014 (co-facilitated NCPES workshop)• NAEDI conference 2015• James Lind Alliance Priority setting workshop on anaethesia and perioperative care

2015• European Lung Foundation to discuss patient priorities for website 2015• EFGCP/EORTC multi-stakeholder event on research lay summaries across Europe 2015• Reading…. Including ‘Emperor of all Maladies’, ‘Anti Cancer’, ‘Cancer is a word not a

sentence’ and others written by clinicians• Listening to others including clinicians, patients, researchers, scientists, peer

consumers, CNS, academics and other professionals

Informed patient?

• Scary statistics – largest killer cancer• 2nd most common cancer in UK• 120 cases diagnosed every day in UK• 1.83 million new cases diagnosed worldwide 2012• 43463 UK diagnoses in 2011– 1 in 7 all cancer

diagnoses• 35371 deaths (2012)• Postcode lottery – wide variations in treatment

offered and success rates

Macmillan’s ‘Cancer’s unequal burden’ report 2014

• 5% predicted to survive 10 years• 89% due to lifestyle/other risks (i.e. 11% not)• Fewer than 1 in 3 live a year or more after diagnosis• 1 in 5 (21%) die within 1 month of diagnosis. 56% die within 6

months and 73% within 1 year. • Fewer than 1% will survive long term in good health. 1 in 20 (5)

live for at least 7 years but most will have 1 or more of a range of other serious health conditions.

• 31% die within 6 months of diagnosis despite cancer not spreading beyond their lungs.

• UK LC patients 10 times more likely to die within a month of diagnosis than breast cancer and twice as likely to die within a month of diagnosis as LC patients in Sweden.

Outlook? • Surgery is one of few curative treatment options with profound bearing on

survival. Earlier diagnosis needed to improve outcomes and reduce variance between Trusts

• Interesting research on surgery for older patients and in previously unconsidered stagings

• Significant improvement in LC services by Trusts employing specialist LC surgeons – (although wide variation)

• Good data collection identifying most successful and outlier Trusts. 6 fold variation in radical resection rates across England.

• Clinical trial participation very patchy – very poor in many Trusts – 25 Trusts not recruited any patients into a single clinical trial (NCIN)

• Results for 1 year relative/net survival increased across all stages in 2012 compared to 2004-7 . 12% absolute improvement in stage1, 11% in stage 2, 10% stage 3 but no change for stage 4.

• LC research global race and challenge

Other breakthroughs/options• SABR - promising results• Immunotherapy – targeted therapies SMP/lung matrix• Sniffer dogs – electronic noses• Global research – different countries/Pharma/industry partners• More research underway• More trials underway• However – each conference revealing widening gaps between

countries, • UK still very poor outcomes at all stages of cancers (except breast),• Complex issues – staffing, skills, dated equipment, higher radiation

levels in CT, shortage of radiographers, access to novel agents or expensive treatments, split in commissioning/Public Health (screening/treatment/referrals/ CCGs) Etc etc

So which patients did you mean? • Those at the recent European Lung Foundation workshop who having met one patient from Aberdeen on a

trial believe the whole of the UK have access to ‘wonder’ treatments

• The German lady who attended this now lobbying her insurance company to pay for such treatments

• Those who believe their treatment is less than optimum

• Those who lobby for greater involvement in research design (such as NCRI CSGs/CLG/CLF)

• Those newly diagnosed

• Those who fear the diagnosis having lost loved ones when treatment options were much more limited and less was known about the disease

• Those participating in online forums/closed groups to share hopes, fears, things that may work for us, those desperately seeking cures/treatments/trial information

• Those who suspect or fear recurrence

So which patients did you mean? (2)• Those, like Lynn, who despite familiarity with medical websites and hospital

information systems, couldn’t navigate her way through available trials and died Feb 2015 4 years after being given months to live

• Patient groups who inform one another • Those who attend conferences seeing the latest research findings only to discover

they don’t change clinical practice or improve patient outcomes

• Patients who raise funds for charity and further research not realising where the money goes nor if/where research data may be published

• Patients who may have unrealistic expectations and raised hopes after reading a new headline (misinformed)

• Those who sit on CSGs and still find difficulty navigating way through the data on available trials to inform others

What does it mean to me?• Frustrated

– at various levels of ignorance about LC early detection, prevention, diagnosis, treatment options and survival rates even amongst clinicians and commissioners

– At lack of shared data– At length of time research takes– At disconnect between world class research, registeries and poor outcomes at all stages for UK LC patients– At rigour of academic science at expense of patient treatments and changing clinical practice

• Excited at collaboration between industry, medics and scientists but– Where is the patient voice? – What is optimum route for patient choice?– Who is responsible for improving medical awareness of research?

• Passionate about opening access and spreading the word – – Even those in the system or articulate/familiar with healthcare struggle to navigate information and find out how to get onto

trials – patients often willing to travel anywhere if it offers hope or longer life– Need to raise awareness amongst general public about risk of LC irrespective of smoking history

• Convinced of the need to reduce and remove stigma – nihilism – rife amongst media and professionals! Patients are not all to blame!

• SMP may still be in its infancy but the expectations are high!

Who are these patients? Are these how you see patients?

Scans, slides, tissue samples, x-rays, digital images, slices??

Cancer types?Stage of disease?Age/gender/smoking status/exposure to carcinogens/deprivation level/poor educational

attainment/social status?

Or something more??

Are we people? With feelings, families, hopes, jobs, dreams?

Who are these patients? Images described at conferences- top row and second row, never smokers (RIP Sian Busby, Cassandra Jardine, Lyn Barrington)

Patient Preferences

• Access to the right diagnostics and best treatment for their cancer

• Right treatment, right time, right place• Free of charge• Risk free• Patient choice• Guarantees• Assurance• Information presented in plain language that can be

understood at difficult times

Patient Preferences (2)

• Timely referral • Quicker results from any tests• Facts• Support• Signposting to others who can help• Ability to travel if able to other centres• Reliable quality and safe services• Minimal side effects• To be asked about research or trial opportunities• Patients are not all the same!

It’s OK to Ask!• Views about perception of care is significant – that counts for a lot so please remember to ask

• Different patients have different views at different parts in their journey

• One day, it could be you – wouldn’t you want to be asked?

• Patients expect research to be published irrespective of outcome to benefit others

• Patients expect data to be shared for advancing research (not recognisable patient data but the science behind it)

• Treatments following research are only useful if they can be accessed

• Is it ethical to approve clinical trials if NiCE would not approve the payment through the NHS?

• Should we lobby for a Cancer Treatment Fund rather than a Cancer Drugs Fund?

• Shouldn’t other treatments such as radiotherapy and surgery be considered on their merits dependent on the cancer type and stage and patient fitness?

• How do we raise awareness amongst policy makers regionally, nationally and internationally that the goalposts are changing so new methods of commissioning/treatment funding are needed?

• Medicines are only of use if they reach patients. Payment frameworks need to change as the cost of developing these will reflect the additional complexity of stratification as well as diagnostic development and will be used by smaller patient numbers but the prize is potentially huge!

• Need to reduce variation and level playing field between nations, sites and cancers

Involving patients• Journeys may be different

• Many people don’t know how to react

• My Respiratory consultant suggested involvement –I am now involved….

• Met TYA consumer rep at NCRI conference 2013 who changed my thinking/approach – Stephen Sutton

• Realised I could use my experience for good and contribute personal and professional experience to improve situation

• Met inspirational and supportive people – humbling.

• You don’t have to put it all ‘out there’

• There is support – books, information, websites, social media, face to face groups, researchers, clinicians, charities, community groups

• Many of us have networks and experience from all walks of life that can help the cause…. Just ask!

• I have been pleasantly surprised by support from strangers!

Advice to clinicians and researchers

• Listen to and involve the customer/patient - -when I met a researcher on SMP, he’d never met a patient!

• The journey isn’t linear and differs amongst individuals

• Encourage others to learn, follow up and lifestyle implications

• Identify resources to help them and you

• Symptoms vary considerably

• Keep up to date –– new routes, new treatments, new research

• Scientists are passionate about disease heterogeneity– Recognise patient heterogeneity! We are more than cells or science!

• Join pathway and integrate services between primary and secondary care to provide seamless support to patients

• Remember patients’ mental health needs as well

• Get a decent 21st century computer system that can share data!

What next?

• Joining the dots … connecting isolated bodies/organisations/individuals

• Hungry to learn and contribute where best able

• Direction of travel moved from FEAR to HOPE

• I’ll continue to do my bit (inspired and humbled by Lyn, Stephen and others who lost their lives)

• What will you do?

Thank you

Janette Rawlinson

Independent Committee Member Sandwell & West Birmingham ClinicalCommissioning GroupNCRI Clinical Studies Group (lung)NIHR HSDR board lay memberCRUK SMP governance board member

Janette.rawlinson@blueyonder.co.ukTel 07903 144360

Acknowledgements : With special thanks to Mr Ehab Bishay and Dr Imtiaz Ahmed for their treatment and support and Dr Marianne Nicholson for her encouragement