Improving research in palliative and end of life care: what, why, - - PowerPoint PPT Presentation

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Improving research in palliative and end of life care: what, why, how, where, when, who?

Prof Irene J Higginson

Cicely Saunders Institute Department of Palliative Care, Policy & Rehabilitation King’s College London

www.csi.kcl.ac.uk @ij_higginson @csi_kcl @cicelysaunders1

www.csi.kcl.ac.uk

Outline

• Why do research in pallia4ve care?
• Whose business is it?
• Landscape of research ac4vity in France…
• Research designs and solu4ons for tomorrow

– Fast track randomised trial – MORECare statement for complex interven4ons – The right outcomes

• Discussion and next steps?

Download presenta.on: www..nyurl.com/parisCSI

TwiGer @CSI_KCL

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Why do research in pallia3ve care?

• Evidence based prac4ce to improve care

quality

• Training opportunity, doing the trials of

tomorrow

• Cri4cal enquiry – finding out what works
• Recogni4on of the uncertainty of

effec4veness underpinning many treatments

• To provide beGer care for pa4ents and

those close to them in the future .. AND NOW

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The landscape of research in pallia3ve care in France?

• Survey of 420 pallia4ve care departments in 2014,

382 responses

• Only 92 (24.1%) involved in a research project during

the last 5 years.

• Challenges as to why not:

– Lack of 4me (80%), … – Pa4ent issues (47%) … ? – Lack of methodological support (33%) – Lack of financial resources (30%)

Rhondali et al BMJ Supportive & Palliative Care 2014;4:182-189.

But do you have time NOT to research?

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No 3me for research? What is the basis for clinical decisions?

Evidence based medicine or one of the alterna4ves?

Isaacs D, Fitzgerald D. BMJ. 1999 Dec 18-25;319(7225):1618

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Finnish Leukaemia Group 1979 – 1985 introducing clinical trials into 17 out of 21 hospital districts in Finland for the treatment of mul4ple myeloma matched to comprehensive Finnish registry data “A natural experiment”. District Outcomes Trial districts 24 38% R. Survival Others 28 28% R. Survival Karjalainen S, Palva I. BMJ 1989 Oct 28;299(6707):1069-72.

Whose business is it? Do research ac3ve healthcare services deliver beNer healthcare? …. YES

PaGern of care and impact of par4cipa4on in clinical studies on the outcome in ovarian cancer, Du Bois et al, Int J Gynecol Cancer 2005, 15, 183. (Germany) Cross-sec4onal rela4onship: research ac4ve hospitals appeared to have lower mortality. PLOS One, 2015 (England)

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Pa3ent issues? Do our pa3ents and

families want to take part in research?

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Pa3ent & Public Involvement at the heart of PC research: examples from Cicely Saunders Ins3tute (CSI)

Videos from several user representa4ves Go to our You Tube channel to see Soap Box Cynthia Benz: hGps://www.youtube.com/watch?v=WvPEGfozVtI hGps://www.youtube.com/watch?v=SebZ-83WG3I hGps://www.youtube.com/watch?v=wYxvzWyAyyQ hGps://www.youtube.com/watch?v=_St3Mbcekrs

Engagement in the planning and design of the Ins4tute, in all studies, plans..

Research carried out with or by members

• f the public/ pa4ents

rather than to, about

• r for them

(INVOLVE 2012)

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Study design: choice

Aim determines the design, essentially four (plus one) main categories of design 1. To explore, describe

– Descriptive studies / surveys / quantitative or qualitative

2. To explore whether something is related to something else (analytical)

– Quasi-experimental, analytical – e.g. cohort (longitudinal study with two groups different at the start), time-series, geographical, (case control) studies, natural experiment, mixed-methods

3. To make sense of a situation, develop new theory, model, relationships

– Qualitative, grounded theory, ethnographic, mixed methods

4. To test whether something causes something else, or if a new service or treatment is effective

– Experimental or intervention studies, can be mixed methods

• Systematic literature reviews – can combine the literature to describe
• r be analytical or can combine experiments

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Experimental studies, traditional options in randomisation

Parallel design Crossover trial Cluster randomisation Patient preference trial

• Individual patients

as they are referred/ identified

• Optimal and most

common approach

• Challenges include

– if ‘control’ group drop out more than intervention group,

• r people try to

‘substitute for intervention group’

• Patients randomly

allocated to different treatment sequences

• Simplest: AB/BA – half
• f patients receive

treatment A, followed by control/B, half receive control/ treatment B followed by A

• Only suitable for those

interventions with short-term effect and can be difficult to work

• ut wash out period
• Randomisation unit is

group of individuals instead of individual patients

• i.e. all patients in a

health district or on a ward or GP practice

• Good especially if

there is ‘education’ in the intervention

• BUT need very large

numbers

• May struggle to recruit

in control

• Individual

patients are randomised but those with a strong preference are not randomised but allocated preferred treatment

• BUT need large

numbers, as analysis is really between the groups without preferences

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How did we come to think of a fast- track randomised trial?

• Recommenda4ons to extend pallia4ve

care to non-cancer condi4ons but liGle evalua4on

• People severely affected by mul4ple

sclerosis (MS) have unmet needs – symptoms, disability, effect on family

• Developing a new (short term) pallia4ve

care service for people severely affected by MS

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Fast-track Randomised Controlled Trial (RCT)

• Names – delayed-intervenKon, wait-list, delayed-

start trial

• All pa4ents will eventually receive interven4on, but

some receive it later than others

• Pa4ents are randomly allocated to interven4on
• Pros – uses randomised design, but gets over

problem of feeling some pa4ents never receive service/treatment

• Cons – can’t use in short survival, some people may

not want to wait

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History of wait-list / delayed interven3on RCT

• Originated from idea of recrui4ng people from a ‘real’ wai4ng list

into a trial. E.g. A randomised controlled trial of methadone maintenance

treatment versus wait-list control in an Australian prison system. Dolan KA, et al Drug Alcohol Depend. 2003 Oct 24;72(1):59-65.

• Others follow all people in trial – E.g. The value of service dogs for

people with severe ambulatory disabilities. A randomized controlled trial. Allen K,

Blascovich J. JAMA. 1996 Apr 3;275(13):1001-6.

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First successful ‘fast-track trial’ in palliative care among people with Multiple Sclerosis

Higginson et al BMC Palliat Care 2008;7:7

We designed the study – aim to recruit 50 patients in one year

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Second fast-track trial, early pallia3ve care, triggered by Breathlessness

Higginson et al. Lancet Respir Med 2014;2(12):978-87

• Early pallia4ve care

integrated with respiratory services

• 16 % improvement in

QoL

• No difference in costs

to health care

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Complex Interven3ons and Pallia3ve and End of Life Care

Pallia3ve care – which are the “ac3ve ingredients”?

• Highly trained staff?
• Suitably designed premises & facili4es?
• Ethos?
• Assessment process?
• Absence of compe4ng demands and priori4es in terms
• f pa4ent mix?

Outcomes are complex, mul4ple and ouen interact or are ac4ng in a changing situa4on (e.g. dying)

TwiGer @CSI_KCL

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Why does it maNer?

addi3onal problems for evaluators, over and above usual prac3cal and methodological difficul3es, E.g.

• difficulty standardising the design and delivery of the

interven4ons (e.g. treatment, service, pathway)

• and of the control group
• sensi4vity to features of the local context, may not be

replicated

• organisa4onal and logis4cal difficulty of applying

experimental methods to service or policy change

• length and complexity of the causal chains that link

interven4on with outcome

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Why does it maNer?

Consequences of failing to recognise you are dealing with complex interven3ons:

• Failed studies – when the interven4on has an effect
• Posi4ve studies – but no one knows what the ac4ve

ingredients are – ‘evalua4ng a ‘black box’ and so it can’t be reliably replicated elsewhere

• Results which don’t apply to anywhere else
• Results which can’t be implemented
• Dangerous implementa4on, failing to recognise key

components that are needed, and missing them

• Cuwng costs by policy makers to implement without key

ingredients, because not shown they are important

TwiGer @CSI_KCL

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Which of the following are ‘complex interven3ons’ in the context of pallia3ve care?

• A new community pallia4ve care service?
• A new outpa4ent clinic?
• A new rehabilita4on interven4on – e.g.

physiotherapy plus educa4on?

• A new care pathway for a care home?
• A new set of advance direc4ves?
• A new analgesic for pain?
• A new an4depressant for depression?

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• Pallia4ve and End of Life Care research presents

its own unique problems

• MRC made a call through the Methodological

Research Programme to evaluate this

• Collabora4on between King’s College London,

University of Manchester, University of Edinburgh and University of Aberdeen with interna4onal Delphi exercises and consulta4on

For all results see: www.tinyurl.com/cicelymorecare

Training see: www.3nyurl.com/MORECareCourse

Development for pallia3ve care: Methods Of Researching interven3ons and services in pallia3ve and End of life Care (MORECare)

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MORECare: Three systema3c reviews

Higginson IJ, Evans CJ. What is the evidence that pallia3ve care teams improve outcomes for cancer pa3ents and their families? Cancer J 2010; 16(5):423-435. Evans CJ, Harding R, Higginson IJ. ‘Best prac3ce' in developing and evalua3ng pallia3ve and end-of-life care serivces: meta-synthesis of research methods for the MOREcare project. Palliat Med. 2013 Dec;27(10):885-98.

TwiGer @CSI_KCL

Gysels MH, Evans C, Higginson IJ. Pa3ent, caregiver, health professional and researcher views and experiences of par3cipa3ng in research at the end of life: a cri3cal interpre3ve synthesis of the literature. BMC Med Res Methodol 2012; 12(1):123.

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Results from Evans, C et al, Palliat Med. 2013 Dec;27(10):885-98 most studies were feasibility context of MRC Framework for development and complex interven3ons

Craig et al 2008, MRC Most studies here, description or early testing of something, never progressing to robust testing & often then introduced widely Many studies also descriptive, repeat ‘admiring’ the problems, rather than finding ways to solve them?

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• 201 pa4ents, pallia4ve care unit
• Of 6276 prescrip4on events, 2199

(35%) were “off-label” (i.e. use pharmaceu4cal drugs for an unapproved indica4on/ route)

• Most common indica4ons for off-

label prescribing were: delirium (36%) and breathlessness (20%). While off-label may be appropriate at times, also can lead to:

• Poor understanding and documentation
• Poor consent process, lacks efficacy of on label, may miss adverse events

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Complexity in pallia3ve care- What is a complex interven3on?

an interven3on (e.g. treatment, service) with several interac3ng components

• Components may act both independently and

interdependently

• Can be difficult to know which are the

“ac4ve ingredients”

• Ouen highly context specific
• Ouen have mul4ple outcomes (intended and

unintended)

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MORECARE recommendations, studies must move from descriptive to actual testing

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Evalua3ng Complex Interven3ons

Ques4on : How many hats does it take to evaluate complex interven4ons in EoL&PC?

Sta4s4cal Analysis health economic assessment Ethics Outcome measurement Mixed Methods Research MRC Guidance

I

TwiGer @CSI_KCL

Answer: Many ... here are the ones we looked at in more detail for the MORECare project

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Main guidance, plus 4 papers and an abstract from the TEC Mostly open access Adaptation for social care research

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MORECARE STATEMENT: 36 points

Recommenda3ons

Introduction/ background 1. Present theoretical framework for the intervention and levels of need established 2. Present objectives appropriate to the level of intervention development Design 3. Indicate and justify stage in MRC guidance for development and evaluation of complex interventions, e.g. feasibility, preliminary evaluation, efficacy / cost effectiveness and wider effectiveness 4. Feasibility stages should test both feasibility of the intervention and of methods of evaluation, including outcome measurement 5. Justify methods, considering appropriate use of existing data sets and secondary analysis as these may produce rapid information 6. Justify methods of empirical studies considering mixed methods, observational studies and randomised trials Study team 7. Ensure involvement from: (i) consumers, patients and caregivers; (ii) relevant clinicians; (iii) relevant methodologists to develop study questions, questionnaires and procedures; and (iv) researchers familiar with the challenges in EoLC studies 8. Ideally involvement should be well established and continuing, beyond a specific study, with joint meetings or rotations between clinical and research staff

Main: BMC Medicine 2013; 11:111

Social care: https://www.sscr.nihr.ac.uk/PDF/MR/MR15.pdf

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• It is ethically desirable to undertake research into pallia4ve

and end of life care and can be unethical not too.

• Collaborate with pa3ent and caregivers in the design of the

study and any ethical aspects to incorporate their comments.

• ANend the ethics commiGee mee4ng with a caregiver or

pa3ent, as a means to help the commiGee beGer understand the pa4ent point of view.

• Ensure propor3onality in pa4ent and caregiver informa3on

sheets, appropriate to the study design and level of risk, as excessive informa4on in itself can be 4ring/distressing for very ill individuals.

• Allow for reflec3on and comment in the ques4onnaires?
• Create a Research Ethics Network for Pallia4ve and End of

Life care to further and disseminate best prac4ce.

• Train those working in on ethics and governance

commiGees in the specific issues and wishes of pa4ents in pallia4ve and end of life care and their families.

• Review and amend the law regarding consent so that

advance consent for studies other than clinical trials of medicinal products applies. www.csi.kcl.ac.uk

Gysels et al Palliat Med. 2013 Dec;27(10):908-17.

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• take into account any poten4al therapeu4c

effect of qualita4ve interviews where par4cipants can express their feelings, if these are similar to components of the interven4on

• ensure research nurses or those collec4ng data

are appropriately trained in qualita4ve data collec4on Mixed Methods Development Pilo4ng Evalua4on Implementa4on components Integra4on Mixing paradigms Space to publish all data Costs Evalua4ons of Complex Interven4ons TwiGer @CSI_KCL

• ensure appropriate mul4-disciplinary skills mix or training of

team define the theore4cal paradigm, method of integra4ng results and safeguards to ensure rigor at the outset

• plan inves4ga4on carefully to avoid undue burden of

qualita4ve and quan4ta4ve ques4onnaires – perhaps dividing data collec4on or selec4ng ques4ons and/or samples appropriately J Palliat Med. 2013 Dec;16(12):1550-60.

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Outcome measurements

When should the primary outcome or end point be measured? A trade

• ff between attrition

and time for the intervention to have an effect. Choose an

• utcome measure

that is validated in

• ne setting or

several?

Some challenges

Should I use staff, patient, observer, or proxy/caregiver reported measures

TwiGer @CSI_KCL

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Recommenda4ons Median (1st - 3rd quar4le) Other proper3es ...Valid and reliable in the relevant popula4on 8 (7-9) ... Use a measure that can be integrated into clinical care 8 (7-9) ... Data from pa4ents and proxy measures should be differen4ated in the dataset. 8 (7-9) Recommenda4ons Median (1st - 3rd quar4le) Measurement proper3es ...easy to administer and interpret (e.g. short and low level of complexity 8 (7-9) ... applicable across care sewngs to capture change in outcomes by loca4on 8 (7-9) ... responsive to change over 4me and capture clinically important data 8 (7.8-8)

Timing

Time points require clear iden4fica4on to establish a baseline 7 (6-9) Time points need to be established before conduc4ng the evalua4on. 7 (5-8) When prospec4ve measurement is used, end points should correspond to when the effect of the interven4on is expected to take place. 7 (6-8)

Outcomes – top recommenda4ons

www.csi.kcl.ac.uk J Pain Symptom Manage. 2013 Dec;46(6):925-37.

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The tools. Build on what we have and improve: Palliative care outcome scale (POS) developments

1986 1999 2009

2018

2017

POS2 MyPOS POS-E IPOS Dem IPOS5 POS-S3 IPOS Neuro APCA African POS4 STAS1 POS-S3:

POS-S MS POS-S Renal POS-S Parkinson STAS1: Dutch French Spanish

Italian Polish Chinese Japanese

POS2: Chinese

Dutch German Italian Spanish Khmer Punjab Urdu Portuguese APCA African POS4: Afrikaans AsiXhosa isiZulu KwaZulu Luganda Luo +5 other dialects

IPOS5:

French German Italian Polish Portuguese Swedish Turkish + 4 ongoing new valida4ons

IPOS Renal

POS website POS training days X

www.csi.kcl.ac.uk

IPOS version professionelle

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Sta3s3cal Considera3ons – all strong agreement with high consensus

ANri3on is to be expected and if you don’t have aNri3on you may have the wrong popula3on in the study Define and report different types of aGri4on, consider how 4ming of data collec4on effects aGri4on. Taxonomy of missing data to understand different types – ADD – aNri3on due to death; ADI – aNri3on due to illness; AaR – aNri3on at random Inves4gate paGerns of missing data and/or the conduct of the study to iden4fy the cause of missing data, to inform choice

• f imputa4on method.

A clear sta4s4cal analysis plan required that iden4fies how to deal with missing data PalliaKve Medicine 2013; 27(10):899-907.

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Latest research: a new measure POS-E

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Big data: BeNer use of exis3ng data sets for compara3ve

analysis

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MORECare e-learning – the methods of conducting research in palliative care

1: Introduction to complex intervention 2: Selection of outcome measure 3: Use of outcome measure 4: Missing data, Attrition and response shift in palliative care 5: Mixed Methods 6: Ethics CPD, 9 credits Affordable Self-paced

www.3nyurl.com/MORECareCourse

Enrol when you wish English as a 2nd language

Developing and evaluating complex interventions

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Dissemina3on of research vital – is there an issue re: French pallia3ve care research visibility?

• Challenge of visibility of ar4cles

published in French in journals which are not indexed in PubMed (even less without keywords or abstract in English)

• Limited number of abstracts from France at the

successive EAPC ?

• Limited number of abstracts submiGed from France to

PC journal in English ( e.g. Pallia4ve Medicine etc)

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Take Home Messages

• Our science is the science that puts the person before their disease
• The future challenges for palliative care needs

integration of research, education and clinical care..

• Because much more to do – still many symptoms and

problems that need further research and analysis, and growing need

• MORECare eLearning can help to develop skills
• Consider the impact and target group of your study when

deciding to publish in French or English TwiGer @CSI_KCL

• Research is central to pallia4ve care, but it also must address ‘big’ ques3ons

– find solu3ons rather than admiring the problem.. generate evidence not

• pinion…
• Innovate, understand and evaluate new/exis4ng models of care, treatments
• Have the right tools – measures, methods, and use these in clinical care and

research

• Build future capacity, skills, infrastructure, collabora4ons, educa4on