Ideas so far…

REG member comments and suggestions

General comments

• “…the time is ripe for some sort of initiative in the area. Careful thought will be needed as to the best way to tap into

this.” Mike Thomas

• “We should aim to produce research which is applicable to guidelines and which can ensure their longevity &

relevance.”

Daryl Freeman• Most value will be in creating opportunities for face-to-face

opportunities to forge common purpose and expose potential synergies in research interests and methods, and for discussing joint projects…”

Eric Bateman

Defining meaningful outcome measures

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Global measure for systemic therapies: •Development a clinical outcome measure that captures both asthma-related symptoms and comorbidities( such as atopic dermatitis, rhinitis, conjunctivitis and sinusitis). Systemically-acting drugs, such as LTRAs and biologics, influence each of these but have an overall effect on health and well-being greater than the sum of the individual organ-related parts, we need a global assessment measure.

Stephen HolgatePatient-defined outcomes not guideline-defined outcomes, e.g.:

o What level of real-life compliance is optimum?o Higher compliance is not always associated with better disease

management (i.e. more severe patients with greater dependence on therapy)

o Discrete choice experiment (DCE)? Christian Virchow

“Develop novel real-life parameters to evaluate symptoms / quality of life”

Claus Vogelmeier

 

Real-life inhaler selection• What drives successful use of different inhaler

types?Federico Lavorini

• Mis-assigning inhalers can be costly• Optimise device to patient• Challenges:

o Device selection is often governed by national heritageo Physician familiarity with a device and appropriate training

can affect education and outcomes.o Pharma funding discredits results… possibility of

government funding?

• Opportunities:o Study comparing turbohaler vs diskus vs spiromax study

– opportunity for DPI crossover after the sponsored study?o Mundipharma step-down study (from Diskus to

MDI or to Diskus) may provide a signal?

PUBLICATION, COMMUNICATION,DISSEMINATION

Communications

• Congresseso Which ones?o Abstractso Session ideas?o REG prize?

• Publicationso Reviewso Editorialso Manifestoo Letter of intent

Manifesto and letters of intent

Manifesto• The group should develop a manifesto for change, covering the

o Need for improved standards in real-life research o Need for greater recognition and integration of real-life

search in the current evidence baseo Challenges faced by real-life researcho Published in the ERJ or the Lancet Respiratory

Alberto PapiLetter• Publish a letter on behalf of the group (signed by all core

steering committee members) endorsing the value of the initiative. Circulate it to potential sponsors.

Andrew McIvor

Conferences: ERS 2013

• Abstracts:

1. Endpoints for observational asthma studies – the current state of the art

2. The real relationship between adherence and outcomes – a need for more patient-focussed outcome measures

• Deadline February 21st

Conferences: ERS 2014 and beyond

• Resubmit the existing proposal? (submission begins in March 2013)

• Need to lobby for a session in Munich: o Talk with different assembly heads to see who can best promote the

ideas internally to the right assembly or assemblieso REG members could attend each of the respective assembly meetings

in Barcelona to talk about the importance of the issue.o Approach assemblies to suggest poster / poster discussion / oral

communication session(s) dedicated to real-life effectiveness studies

• Could propose a joint symposium with:o The European Lung Foundation (ELF) – look at real-life research

from the patients’ perspective:  “Reflecting the needs of all patients in the real-world”

o Some REG members are involved in the GINA and GOLD committees – a proposal for a common GINA + GOLD + REG session: “How effectiveness studies could be taken into accounted by guideline developers based on some specific examples of evidence.”

Conferences: ERS 2014 and beyond

• Hot topic suggestionso Association between the different biomarkers used in

clinical assessment of asthma (screening and follow-up).o Data from non-selective populations – real-life clinical

settings.o What to be used, and what not e.g: smoking patients, o In case of infrequent dose of inhaled steroid, respiratory

infection within 4 or 6 weeks – what to do ? o A surrogate variable for sputum counting, e.g. sputum

supernatant for IL8 (neutrophilia) or other…?  o Sport:

– Asthma evaluation– Doping and sport

Alternative conferences

Propose sessions to multiple congresses:•EAACI

o “excellent alternative – large meeting with many knowledge-rich delegates”

o “EAACI could be an excellent future collaborative partner”

•IPCRG – Athens 2014: o Plenary – UNLOCK (asthma history / future in COPD);

Using real-life data to answer questions – inhaler type; initiation and step-up options; patient sub-groups (smokers, atopic patients); DOSE index and validation.

o Miguel to propose at scientific committee

•Other options include: AAAAI / ATS / ISPOR / BSACI…?

Congresses: strategic approach

• Need to raise awareness/importance of the topic before acceptance from societies, by:

• Continued abstract submissions to various societies.  o Will slowly gain awareness.

• Continued submissions for a program slot.  o A long shot initially.

• Various journals have supplement journals (such as the Annals of the ATS) that accept a theme topic for the entire supplement.  o Usually has a significant price tag, but REG funding

might afford it and could jump start the awareness and importance aspect of real life trials.  

o Downstream affect would be a society(ies) slot.

Congress: hold our own meeting?• Hold a planning meeting at the ERS in Barcelona:

o Get the group together and plan a strategy and collaborative research projects?

o Brainstorm about holding an REG-organised 1–2 day meeting on this real-life research?

SETTING STANDARDS

Setting standards

• Suggestions so far:o Validation work – discussedo Registry?o Code sharingo Standardising terminology, lexicon and study

design to allow comparisonso Where do pragmatic trials fit?o How to define an implementation study

A real-life study registry

• Provide a registration service for real-life studies pragmatic clinical trials and observational studies.

• Current registries are designed for RCTs – square peg; round hole?

• Benefits:o Mandate entry of meaningful, minimum data entryo Create a central repository or real-life researcho Serve as a quality marker of high-quality researcho Provide “peer review” of protocols at the point of submissiono Stop US monopoly on study registration 

• The respiratory journal editors are going to mandate that all studies MUST be registered (observational, pragmatic trials, RCTs)o Develop the registry in collaboration with the respiratory journal

editors?o The journals editors could promote the registry on behalf

of the group

Code sharing

• Share code lists among the research community• Enable peer review of research codes and

standardisation of coding methods• Share different lists of codes for different coding

systems:o Read codes (UK)o ICD codes

• Host code lists on the REG websiteo Password protected area for members only

• Consider how to combine data sets for maximum power and to gain collaborative experience. o E.g. Pooled OPCRD and CPRD data for the pediatric

asthma study (previously discussed)

Defining standards and lexicon

Protocol review service: • Another task of the group could be to support others when

they want to develop a real-life research project, the group acting as a consultant for methodology.

Nicolas RocheRe-defining the lexicon• Efficacy and effectiveness are too interlinked… they’re often

confused.• Use instead:

o Does the drug work? (efficacy)o Does the drug help? (effectiveness)

– Even placebo can help in the real-world.Christian Virchow  

Pragmatic trials & implementation studies (I)• Are pragmatic trials within the scope of REG – yes…?

• The issues / benefits / limitations associated with different types of real-life research (observational research / pragmatic trials) differ and should be clearly set out.

Mike Thomas

• Eric Bateman and colleagues have conducted several pragmatic randomised controlled trials in large primary care populations – they would be pleased to interact with those interested in large-scale healthcare interventions focusing on respiratory diseases.

Eric Bateman

Pragmatic trials & implementation studies (III)REG should:• Consider publishing a methodology paper on the challenges faced

in real-life research• Define implementation studies. A recent review of the literature

for self-management of long-term conditions found it difficult to:o Set up searches which identify implementation studies o Screen the abstracts due to lack of standard terminologyo Evaluate whether a study was truly possible to implement (due

to poor description of the methodology and inconsistent terminology) – editors tend to view implementation studies as (cluster) RCTs (and apply the checklist) which does not necessarily work

Hilary Pinnock

Pragmatic trials & implementation studies (II)

• It is important to design and undertake:o Pragmatic clinical trialso Population-level implementation studies (e.g.

stepped wedge or interrupted time series)of sufficient quality and designed that they can be assessed by guideline bodies and inform guidance.

Hilary Pinnock

COLLABORATIONS

Collaborations

• Interactions with others…o Guideline bodieso Societies

– GOLD, GINA– EACCI, AAAAI– ISPOR, IPCRG– ERS, ATS…

o Regulatory authoritieso Government departmentso Patient groupso PR and media?

Guidelines: comments

Guidelines: suggested actions (I)WHAT?•REG should accelerate the acceptance of real-life research by guideline writers?

Kevin Gruffydd-Jones, Alberto Papi

HOW?•Evidence grading standards:

Propose quality criteria for different types of real-life research. Standards will assist in deciding whether a study should be taken into account by guidelines bodies

Nicolas Roche

•Grading scale: Develop a quantitative scale for grading evidence along the efficacy to effectiveness continuum (based on the Kevin Thorpe framework).  

Jerry Krishnan 

Guidelines: suggested actions (II)