Maximising the yieldTowards patient-centred care

Dermot RyanRotterdam January 2015

Differing perspectives

Outline of Presentation

• REG: Founding Principles• Guidelines: are they failing?• Overview of Rotterdam 2015

REG: founding principles• Registration, randomized controlled trials

(RCTs) have long been the gold standard in evidence-based research.

• RCTs:o Pro: Are important & form the basis for national

and international guidelines. o Con: Have drawbacks – they deal only with

strictly controlled care settings and highly-selected populations, thus they represent only ≤10% of true asthma & COPD patients treated in routine care2

2. Herland Ket al. Respir Med 2005;99:11–19.

REG: Key Facts • An independent, collaborative research and

advocacy network set up in 2012/3 to:o Defragment activities and unifying experts

working in “real-life” (respiratory) researcho Raise the quality and profile of the field o Achieve better integration of evidence from

sources other than classical randomized control trials (cRCT) into clinical practice guidelines.

• Registered as a not-for-profit social enterprise in the UK

Heritage of real-life research

• “Pragmatic trials”: o Studies designed to reflect the real

world (patient types and/or ecology of care) more closely than RCTs4

oDetermine the effects of an intervention under the usual conditions in which it will be applied in contrast to the ideal circumstances that are assessed by RCTs5

4. Schwartz D, Lellouch J. J Chronic Dis 1967;20:637–648.5. Thorpe KE, et al. CMAJ 2009;180:E47–E57.

The need for a diversity of approaches“Randomized controlled trials, long regarded as the ‘gold standard’ of evidence, have been put on an undeserved pedestal. Their appearance at the top of ‘hierarchies’ of evidence is inappropriate; and hierarchies, themselves, are illusory tools for assessing evidence. They should be replaced by a diversity of approaches that involve analyzing the totality of theevidence-base”3

3. Rawlins M. Harveian Oration. Royal College of Physicians, London England. 16 October 2008

The Arch Declaration• Comprises: 7 papers

discussing the key themes of the Arch Summit –the inaugural meeting of the Respiratory Effectiveness Group (REG)

• Objective: to help move the entire area of pragmatic and observational research forward so it becomes better incorporated into clinical practice decisions for the benefit of patients, practitioners, and other stakeholders

What are guidelines?

• A guide to clinical decision making• A compendium of (some) current evidence• An attempt to standardise care• Useful repository of knowledge• An excellent learning/training framework

Are guidelines failing…?• Used by managers

and politicians• Impair

clinical/deductive reasoning skills in clinicians

• May impede research

• Frequently do not apply to the individual patient

Types of careGuideline-directed care• Top-down “cookbooks”2

• Focus on disease rather than patient

• Do not account for comorbidities or confounders1

• Overlook variations in patients and care settings

• Overlook the interaction between “the world” & patient characteristics and “idealised” outcomes3

• Cost effective?4

Patient-centred care2

• Evidence-based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients

• without clinical expertise, practice risks being tyrannised by evidence1. Boyd C.JAMA. 2005 Aug 10;294(6):716-24; Sackett BMJ. 1996; 312(7023): 71–72;

4. Price D. Breathe 2015 (In press); 3.Vigersky Diabetes Care 2013 3849:36;

EBM: the three-legged stool

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Experience

Training

Research

Guidelines

Judgment

Care System

Costs

Availability

Clinical Practice

• Studies have shown that efficacy RCTs exclude about 95% of asthma and 90% of COPD routine care populations due to strict inclusion criteria.1

1. Herland K, et al. Respir Med 2005;99:11–19.

Limitations: RCTs inclusions/exclusions

COPD

Asthma

Patient RCT eligibility drop-off with sequential application of standard inclusion criteria

Improving guidelines: evidence appraisal• Sir Michael Rawlins, the former chairman of the

UK’s National Institute for Health and Care Excellence:1

o Hierarchies of evidence are over-simplistic and offer a pseudoquantitative assessment of the available evidence.

o All forms of evidence should be considered, while taking into account the limitations and strengths of their respective designs

o Differently designed studies should be considered as complementary and should be used in combination by guideline developers to help inform their judgments and recommendations.

1. Rawlins M. De testimonio: on the evidence for decisions about the use of therapeutic interventions. Lancet 2008;372:2152–2161.

New Guidelines: GINA 2014

GINA recommendations• recognise variability and

heterogeneity• individual patient characteristics• tailoring care• patient preference• practical issues

Other therapy areas• Researchers identified 65 studies, mostly case series and

observational post-marketing surveillance studies, that addressed risk for lactic acidosis in patients with type 2 diabetes.1

• Patients with mild-to-moderate CKD who use metformin have slightly elevated but not clinically worrisome lactic acid levels.

• Among all patients with type 2 diabetes, observational studies showed no excess risk for lactic acidosis in patients who took metformin.

• Moderate CKD (estimated glomerular filtration rate [eGFR], 30–60 mL/minute/1.73 m2) reduces metformin clearance, but metformin levels remained within the safe range.

• Limited data, BUT.. Suggest substantial excess risk (6- to 7-fold) for diabetic patients with severe CKD (eGFR, <30 mL/minute/1.73 m2)1. Inzucchi SE et al. Metformin in patients with type 2 diabetes and kidney disease: A systematic

review. JAMA 2014 Dec 24/31; 312:2668. (http://dx.doi.org/10.1001/jama.2014.15298)

Enhancing guideline utility (I)• To achieve their goal of helping to guide the

meaningful implementation of new research into practice, for the benefit of all stakeholders, clinical guidelines would benefit from:o Wider stakeholder representation within

guideline committees (e.g., patients, primary and secondary care clinicians, policy makers, and health insurers) while still respecting the rules of evidence evaluation

o Keeping the ideas of “usability” and “readability” at the forefront of the development process

o Integration of effectiveness data as well as efficacy data into recommendations.

Enhancing guideline utility (II)• Guidelines must provide a wider view of the

management of diseases, one that reflects the diversity of decisions faced by clinicians.

• When conducting evidence reviews, guideline committees should consider not only the robustness of the available data but also its applicability.

• Evidence from effectiveness studies—pragmatic trials and observational studies—should be more consistently incorporated when assessing the risks and benefits of different care strategies. In some cases, (e.g., understanding the long-term sequelae of therapy), observational studies (rather than clinical trials) are needed.

Guidelines need to: Encompass all patients1

Reflect human behaviour2

Ensure they are applied to the correct patients ( diagnosis) Incorporate patients view by exploring their Ideas, concerns and

expectations2

Identify barriers to implementation• Relevance: achievability• Patient: social, pyschological, behavioural• Societal: costs, access, structures, billing and reward systems• Professional: CME, costs, access, tradition

Recommend management by strata Workforce planning Training needs Describe care pathways3

(Perhaps) lend themselves to decision support systems

1.Family Practice (2010) 27 (1): 1-2. doi: 10.1093/fampra/cmp1062 CHEST. 2006;130(1_suppl):65S-72S. doi:10.1378/chest.130.1_suppl.65S Horne and Weinmann3. Integrated care pathways for airway diseases (AIRWAYS-ICPs) Eur Respir J, doi:10.1183/09031936.00014614

What proportion of the population’s

needs are met by guidelines?

Different guidelines for different populations?

Primary Care1 Specialist Care2

1. ‘SIMPLES’: a structured primary care approach to adults with difficult asthma

2. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

Individual Characterisation

ASTHMAPhenotypes1

1.Haldar et al Am J Respir Crit Care Med. 2008;178:218–224

How will we achieve this?

DATABASESDifferent databases contain information that can inform us about a range of aspects of disease:• Prevalence• Variability• Effectiveness• Costs• Medications• Outcomes

• Aid examination of disease and treatment effects in different healthcare systems.

• Allow us to draw inferences from what is seen.

• Allow us to determine infrastructural, educational, training, work-force needs.

• Permit us to make projections.• Permit observation of what happens in real

life.

Database opportunities (I)

• Permit us to identify gaps in our knowledge.

• Fosters dialogue between professionals and pharma.

• Informs dialogue between professionals and health ministries.

• Identify which healthcare systems perform better.

• Permit patient advocacy.• Test hypotheses to help design future

Phase IV trials.

Database opportunities (II)

Hypothesis testing

• Test the same hypothesis in different datasets

• Permits testing of robustness of data

• Tests applicability

• Pool “like” datasets to test an hypothesis

• Greater power

Disease-specific databases• Drawn from disease registers of more

circumscribed and well-defined respiratory problems, e.g.:o Lung cancero Cystic Fibrosiso ILD

• Aggregate information from different centres• More likely to be of higher quality• Because of their relative size, may give insights

into to how to better use larger databases.• Provide clues as to management optimisation• Help inform future development of care pathways

Database: limitations & solutions• Limitations

o Inaccurate diagnosiso Codingo Confidentiality

• Potential solutions:o Design databaseso Develop a common language & common

codingo Standardised criteria for entry (e.g. confirmed

diagnosis)

Database design

• What are the key clinical criteria required to address basic research questions? 

• How do the key clinical criteria differ for different respiratory diseases?

• What additional criteria would be useful for more involved research questions?

• What are the ethical implications and how should data be stored and formatted?

• How REG could provide guidance for countries seeking to develop national, regional, cohort, etc databases in the future?

For discussion this afternoon in the:“DESIGN A DATABASE SESSION”

Inhalers

• Most common route of administration of respiratory meds.

• Difficult to use, critical errors.1,2

• Ignorance by medical workforce.3

• Responsible for poor compliance?4

• Responsible for treatment escalation?

1. Molimard. J Aerosol Med 2003; 16 (3):249–254.2. Giraud. Eur Respir J 2002; 19 (2): 246–251.3. Plaza. J AerosolMed Pulm Drug Deliv. 2012;25(1):16–22.4. Harnett. Journal of Asthma 51:4;440-5

New device data to be presented in this afternoon’s thematic abstract session: “DEVICES IN THE REAL WORLD”

Next generation inhalers

• Easy to teach• Easy to use• Patient feedback• Electronically linked:

o Compliance 1,2,3

o Technique 1

o Aided self management2,3

• Deployment: opportunities/barriers

1. D'Arcy S, PLoS One. 2014; 9: e98701.2. www.smartinhaler.com. 3. www.propellerhealth.com

Biomarkers

• Estimation of severity• Indications for treatment• Identification of high risk patients

Presentations on• Predictors of Asthma Risk• Eosinophilia in COPD

New risk prediction data to be presented in this afternoon’s:

“LATE-BREAKING ABSTRACT SESSION”

Diagnosis and Management

• Diagnosis is a crucial achievement• Many patients on asthma/COPD registers

do not have that disease• Orphan areas such as ILD, Alpha1

deficiency• Initial management: what drugs are

chosen?• Comparative effectiveness of different

preparations

Tomorrow’s plenary and abstract sessions will look at an ILD database, real-life

diagnosis and management data

Therapy adherence

• What affects adherence: life-threatening events/exacerbations?

• How may adherence be measured?• Does switching affect adherence?Questions that will be addressed in

tomorrow’s thematic abstract session

Patient-centred Care

• Applies evidence to the specific needs of the patient

• Database evidence complements and supplements cRCT-based guideline recommendations

• Implementation remains a challenge

Other activitiesWorking groups:

• Asthma• Small airways• COPD-control• Adherence• Accreditation• Research Review• Database• Cost-effectiveness

• Child Health• Cost effectiveness• IPF/ILD• Manuscript review• ACOS• Validation and

Standardisation of coding

Types of careGuideline-directed care• Top-down “cookbooks”2

• Focus on disease rather than patient

• Do not account for comorbidities or confounders1

• Overlook variations in patients and care settings

• Overlook the interaction between “the world” & patient characteristics and “idealised” outcomes3

• Cost effective?4

Patient-centred care2

• Evidence-based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients

• without clinical expertise, practice risks being tyrannised by evidence1. Boyd C.JAMA. 2005 Aug 10;294(6):716-24; Sackett BMJ. 1996; 312(7023): 71–72;

4. Price D. Breathe 2015 (In press); 3.Vigersky Diabetes Care 2013 3849:36;

REG

Bridging the gap

Using data

Designing trials

To enhance individualised,

patient-centred care

Real-life evidence

Data base work

Pragmatic trials

REG

Maximising Yield

RCTs

Guidelines

Training Skills

Pathways

Devices

Diagnosis

InvestigationStratification

Management

REGactivities

Accreditation

Collaboration