The Gift of the The Gift of the OMERACT Filter OMERACT Filter - - PowerPoint PPT Presentation

The Gift of the The Gift of the OMERACT Filter OMERACT Filter

Jasvinder Singh, MD, MPH Jasvinder Singh, MD, MPH

Sincere thanks to Maarten Boers, MSC, MD, PhD at Sincere thanks to Maarten Boers, MSC, MD, PhD at VU VU University Medical Center University Medical Center Amsterdam, Netherlands Amsterdam, Netherlands for for slides slides

Jasvinder Singh, MD, MPH Jasvinder Singh, MD, MPH

University of Alabama at Birmingham University of Alabama at Birmingham Birmingham Veterans Affairs Medical Center Birmingham Veterans Affairs Medical Center Mayo Clinic College of Medicine Mayo Clinic College of Medicine

On Behalf of the OMERACT Steering Committee On Behalf of the OMERACT Steering Committee

Outline Outline

What is a core set and why do we need them? What is a core set and why do we need them?

Issues with Trials Issues with Trials

Current initiatives to develop core sets Current initiatives to develop core sets

Outcome Outcome Measures in Measures in Rheumatology ( Rheumatology (OMERACT OMERACT) Core Outcome Measures in Effectiveness Trials Core Outcome Measures in Effectiveness Trials Core Outcome Measures in Effectiveness Trials Core Outcome Measures in Effectiveness Trials (COMET (COMET)

Existing definitions, conceptual structures Existing definitions, conceptual structures and their history and their history OMERACT proposal for core areas of measurement OMERACT proposal for core areas of measurement

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Problems with trials Problems with trials

Trials are done to evaluate Trials are done to evaluate whether an intervention is effective and safe whether an intervention is effective and safe Choice of measures to reflect benefit and harm Choice of measures to reflect benefit and harm In most areas choices not standardized In most areas choices not standardized In most areas choices not standardized In most areas choices not standardized

heterogeneity between trials heterogeneity between trials potential for bias (selective outcome reporting)

• tential for bias (selective outcome reporting)

c choice of measures less relevant to users hoice of measures less relevant to users

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Solution Solution

Development of Development of trial core sets trial core sets Minimum inimum set of set of outcomes that

• utcomes that should be

should be measured and reported in all clinical trials measured and reported in all clinical trials

• f
• f a specific

a specific condition condition What is an outcome? What is an outcome? How to decide what belongs in a core set? How to decide what belongs in a core set?

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“O utcome utcome ME ME asures asures in in R heumatoid heumatoid A rthritis rthritis C linical linical T rials rials”

Outcome Measures in Rheumatology* Outcome Measures in Rheumatology*

Informal, unofficial Informal, unofficial Group of health professionals and Group of health professionals and patient experts interested in outcome patient experts interested in outcome measures and endpoints in rheumatology measures and endpoints in rheumatology

* www.omeract.org

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Rheumatology, 1980 Rheumatology, 1980-

• 1990

1990

No consensus over No consensus over which measures to include in RA trials which measures to include in RA trials

> 25 different measures available > 25 different measures available 5 meetings: no single consensus 5 meetings: no single consensus 5 meetings: no single consensus 5 meetings: no single consensus

Confusion: purpose, focus of measurement, Confusion: purpose, focus of measurement, and selection of measures and selection of measures Increasing recognition of the importance Increasing recognition of the importance

• f
• f sensitivity to change

sensitivity to change Transatlantic divide Transatlantic divide

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OMERACT 1 OMERACT 1

Maastricht, 1992 Maastricht, 1992 Core set for RA trials Core set for RA trials Minimum relevant improvement Minimum relevant improvement patients/trials patients/trials patients/trials patients/trials Composite measures/ Composite measures/ improvement criteria improvement criteria

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WHO/ I LAR WHO/ I LAR core set core set RA clinical trials RA clinical trials

global assessments patient & assessor global assessments patient & assessor pain pain painful joint count painful joint count swollen joint count swollen joint count swollen joint count swollen joint count physical disability physical disability acute phase protein acute phase protein

in studies ≥ 1 year: X in studies ≥ 1 year: X-rays hands & feet rays hands & feet

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OMERACT 11 OMERACT 11

(Pinehurst, 2012) (Pinehurst, 2012)

preconference symposium preconference symposium

CAT/IRT CAT/IRT

mini mini-

• module

module

Psoriatic Arthritis Psoriatic Arthritis

workshops workshops

Worker Productivity Worker Productivity

extra activities extra activities

Fellow training Fellow training

extended interest group extended interest group

Flares in RA Flares in RA

special interest groups special interest groups

Myositis Myositis Worker Productivity Worker Productivity Acute Gout Acute Gout Ultrasound responsiveness RA Ultrasound responsiveness RA Vasculitis Vasculitis OMERACT Filter 2.0 OMERACT Filter 2.0 Truth: Areas/Domains Truth: Areas/Domains Truth: Instruments Truth: Instruments Discrimination & Feasibility Discrimination & Feasibility Putting it all together Putting it all together

Patient Reported Outcomes Patient Reported Outcomes Imaging & Biomarkers Imaging & Biomarkers

Myositis Myositis MRI MRI-

• Juvenile Infl. Arthritis

Juvenile Infl. Arthritis PROMIS PROMIS Hand Osteoarthritis Hand Osteoarthritis Equity Equity Polymyalgia Polymyalgia Rheumatica Rheumatica MRI MRI-

• inflammatory arthritis

inflammatory arthritis Item Response Theory Item Response Theory Hip Osteoarthritis Hip Osteoarthritis Connective Tissue Disease/ Connective Tissue Disease/ Interst

• Interst. Lung disease

. Lung disease

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Bottom line Bottom line

Achieving consensus over measures Achieving consensus over measures involves: involves:

Content Content

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Content Content

Education in methodology Education in methodology Agreeing on: Agreeing on: Purpose Purpose Domain(s) Domain(s) Applicability of specific measures Applicability of specific measures Iteration Iteration

Content Content

Bottom line Bottom line

Achieving Achieving consensus over measures consensus over measures involves: involves:

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Content Content Process Process

Data Data-

• driven

driven Iterative, stepwise Iterative, stepwise Inclusivity Inclusivity Important role for dissenters Important role for dissenters Harsh data softened by political considerations Harsh data softened by political considerations

OMERACT Filter 1.0 OMERACT Filter 1.0 OMERACT Filter 1.0 OMERACT Filter 1.0

OMERACT Filter OMERACT Filter to select measures to select measures

To be applicable in its intended setting, To be applicable in its intended setting, a measure must be a measure must be

truthful truthful discriminative discriminative feasible feasible

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OMERACT Filter OMERACT Filter

Truth Truth

free from bias free from bias

criterion, construct validity criterion, construct validity criterion, construct validity criterion, construct validity

relevant relevant

content, face validity content, face validity

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OMERACT Filter OMERACT Filter

Discrimination Discrimination

able to distinguish between states able to distinguish between states that are of interest: that are of interest: that are of interest: that are of interest:

at one time point at one time point at different time points at different time points reliability, reproducibility, reliability, reproducibility, sensitivity to change sensitivity to change

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OMERACT Filter OMERACT Filter

Feasibility Feasibility

time time costs costs costs costs interpretability interpretability

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OMERACT Filter OMERACT Filter

Filter works best to select instruments Filter works best to select instruments

• nce the
• nce the areas of measurement

areas of measurement have been decided on have been decided on Truth: “…measure what it’s supposed to…” Truth: “…measure what it’s supposed to…” but how to decide on the supposition? but how to decide on the supposition? but how to decide on the supposition? but how to decide on the supposition? For any core set we need to decide For any core set we need to decide in what areas we need to measure in what areas we need to measure core areas of measurement core areas of measurement

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Example Example

WHO/ I LAR WHO/ I LAR core set core set rheumatoid arthritis clinical trials rheumatoid arthritis clinical trials

global assessments by patient & assessor global assessments by patient & assessor pain pain painful joint count painful joint count painful joint count painful joint count swollen joint count swollen joint count physical disability physical disability acute phase protein acute phase protein

in studies ≥ 1 year: X in studies ≥ 1 year: X-rays hands & feet rays hands & feet

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RA core set & outcome RA core set & outcome

Outcome: Outcome: “how a patient feels, functions or survives” “how a patient feels, functions or survives”

patient global patient global pain pain pain pain physical function physical function

Disease activity Disease activity

assessor global assessor global swollen and tender joint counts wollen and tender joint counts acute phase protein acute phase protein

Damage: X Damage: X-rays rays

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Patient input in OMERACT Patient input in OMERACT

started in 2002 started in 2002

Core set is deficient because it does not include Core set is deficient because it does not include enough (patient enough (patient-

• important) outcome measures

important) outcome measures

Fatigue Fatigue Sleep Quality Sleep Quality Sleep Quality Sleep Quality

…Content validity problem! …Content validity problem! …Core area problem! …Core area problem! To decide on core sets, To decide on core sets, we need to define core areas first we need to define core areas first

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OMERACT Filter 2.0 OMERACT Filter 2.0 OMERACT Filter 2.0 OMERACT Filter 2.0

Core areas of measurement Core areas of measurement

Core areas of measurement Core areas of measurement

Def.: areas that should Def.: areas that should always be addressed always be addressed by measures included in a core set for trials by measures included in a core set for trials aimed at a specific health aimed at a specific health condition condition to decide on core areas, to decide on core areas, we need: we need:

a conceptual structure of health a conceptual structure of health and health conditions and health conditions consensus on which areas in this structure consensus on which areas in this structure are core are core consensus on whether core areas are generic consensus on whether core areas are generic

• r specific to a certain health condition
• r specific to a certain health condition

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Definitions Definitions

health health health intervention health intervention core area: core area: aspect of a health condition aspect of a health condition that needs to be measured to appropriately assess that needs to be measured to appropriately assess that needs to be measured to appropriately assess that needs to be measured to appropriately assess the effects of a health intervention. the effects of a health intervention. (sub)domain: (sub)domain: component component of

• f core area

core area: a concept : a concept to be measured, a further specification of an aspect to be measured, a further specification of an aspect

• f health, categorized within a
• f health, categorized within a core area

core area.

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Definitions Definitions

health health health intervention health intervention core core area: essential aspect of a health area: essential aspect of a health condition.. condition.. (sub)domain: construct within a core area (sub)domain: construct within a core area (sub)domain: construct within a core area (sub)domain: construct within a core area

• utcome:
• utcome: any

ny identified result in a (sub)domain identified result in a (sub)domain arising from exposure to a causal factor or a health arising from exposure to a causal factor or a health intervention. intervention. measurement instrument: measurement instrument: a tool to measure tool to measure a quality or quantity of a variable. quality or quantity of a variable.

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Existing conceptual structures Existing conceptual structures and their history and their history

WHO 2001 WHO 2001 International Classification of Functioning (ICF) International Classification of Functioning (ICF)

universal classification of human functionality, universal classification of human functionality, both positive and negative

• th positive and negative

body function & structure activity participation contextual factors (environmental; personal) health condition

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Impact

• f Health Conditions

Pathophysiological M anifestations Concepts

Core Areas for M easurement in Health Interventions

Impact

• f Health Conditions

Pathophysiological M anifestations Core Areas Death Life Impact Pathophysiological M anifestations Concepts

Core Areas for M easurement in Health Interventions

Resource Use/ Economical Impact

Impact

• f Health Conditions

Pathophysiological M anifestations Core Areas Death Life Impact Pathophysiological M anifestations Concepts

Core Areas for M easurement in Health Interventions

Resource Use/ Economical Impact

• ‘lived experience of health’
• AKA ‘Burden of Disease’
• most ‘traditional’

trial measures

• both physical

and psychological

Impact

• f Health Conditions

Pathophysiological M anifestations Core Areas Death Life Impact

Examples

Pathophysiological M anifestations Concepts

Core Areas for M easurement in Health Interventions

Resource Use/ Economical Impact

• disease

Examples

• f specific

Domains within Areas*

• disease
• intervention

* in all areas, domains can be generic or made more specific:

• eg. disease-specific, time specific (eg. short or long-term),

specific for patient preference

Impact

• f Health Conditions

Pathophysiological M anifestations Core Areas Death Life Impact

Examples

• ICF domains: activity

Pathophysiological M anifestations Concepts

Core Areas for M easurement in Health Interventions

Resource Use/ Economical Impact

• disease

Examples

• f specific

Domains within Areas*

• ICF domains: activity

and participation

• quality of life
• patient perception of health
• loss of ability to work
• psychosocial impact
• 2ary impact on family, caregivers
• utility
• disease
• intervention

* in all areas, domains can be generic or made more specific:

• eg. disease-specific, time specific (eg. short or long-term),

specific for patient preference

Impact

• f Health Conditions

Pathophysiological M anifestations Core Areas Death Life Impact

Examples

• ICF domains: activity

Pathophysiological M anifestations Concepts

• societal

Core Areas for M easurement in Health Interventions

Resource Use/ Economical Impact

• disease

Examples

• f specific

Domains within Areas*

• ICF domains: activity

and participation

• quality of life
• patient perception
• f health
• loss of ability to work
• psychosocial impact
• 2ary impact on family,

caregivers

• utility
• societal
• individual
• health care
• direct/ indirect

(productivity)

• intangible costs
• disease
• intervention

* in all areas, domains can be generic or made more specific:

• eg. disease-specific, time specific (eg. short or long-term),

specific for patient preference

Impact

• f Health Conditions

Pathophysiological M anifestations Core Areas Death Life Impact

Examples

• ICF domains: activity
• ICF: body function

Pathophysiological M anifestations Concepts

• societal

Core Areas for M easurement in Health Interventions

Resource Use/ Economical Impact

• disease

Examples

• f specific

Domains within Areas*

• ICF domains: activity

and participation

• quality of life
• patient perception
• f health
• loss of ability to work
• psychosocial impact
• 2ary impact on family,

caregivers

• utility
• ICF: body function

and structure

• organ function

(eg lung function)

• reversible

manifestations

• irreversible

manifestations

• biomarkers
• surrogate outcomes
• societal
• individual
• health care
• direct/ indirect

(productivity)

• intangible costs
• disease
• intervention

* in all areas, domains can be generic or made more specific:

• eg. disease-specific, time specific (eg. short or long-term),

specific for patient preference

Impact

• f Health Conditions

Pathophysiological M anifestations Core Areas Death Life Impact

Examples

• ICF domains: activity
• ICF: body function

Pathophysiological M anifestations Concepts

• societal

Core Areas for M easurement in Health Interventions

Resource Use/ Economical Impact

• disease

Examples

• f specific

Domains within Areas*

• ICF domains: activity

and participation

• quality of life
• patient perception
• f health
• loss of ability to work
• psychosocial impact
• 2ary impact on family, caregivers
• utility
• ICF: body function

and structure

• organ function

(eg lung function)

• reversible manifestations
• irreversible manifestations
• biomarkers
• surrogate outcomes
• societal
• individual
• health care
• direct/ indirect

(productivity)

• intangible costs

* in all areas, domains can be generic or made more specific:

• eg. disease-specific, time specific (eg. short or long-term),

specific for patient preference

Adverse Events

AE’s are measured within the core areas, but are labeled separately to allow assessment of benefit and harm.

• disease
• intervention

Impact

• f Health Conditions

Pathophysiological M anifestations Core Areas Death Life Impact

Examples

• ICF domains: activity
• ICF: body function

Pathophysiological M anifestations Concepts

• societal

Core Areas for M easurement in Health Interventions

Resource Use/ Economical Impact

• disease

Examples

• f specific

Domains within Areas*

• ICF domains: activity

and participation

• quality of life
• patient perception
• f health
• loss of ability to work
• psychosocial impact
• 2ary impact on family, caregivers
• utility
• ICF: body function

and structure

• organ function

(eg lung function)

• reversible manifestations
• irreversible manifestations
• biomarkers
• surrogate outcomes
• societal
• individual
• health care
• direct/ indirect

(productivity)

• intangible costs

* in all areas, domains can be generic or made more specific:

• eg. disease-specific, time specific (eg. short or long-term),

specific for patient preference

Adverse Events

AE’s are measured within the core areas, but are labeled separately to allow assessment of benefit and harm.

• disease
• intervention

Developing a Core Outcome M easurement Set

Death Life Impact Core Areas Resource Use Pathophysiological M anifestations M atch Domains Literature review List of Domains & Instruments Setting/ Contextual factors Stakeholder input Adverse events Draft Core Domain Set

All important stakeholders should be included from the start: patients and their proxies, caregivers, researchers, etc.

M atch Domains to Core Areas Stakeholder input consensus

update cycle

agreement on what to measure

at least one Domain from each Core Area

Core Domain Set

agreement on what to measure

at least one Domain from each Core Area

Core Domain Set

agreement on what to measure

at least one Domain from each Core Area

Core Domain Set

agreement on how to measure

at least one applicable Instrument per Domain

Core Outcome M easurement Set

Developing a Core Outcome M easurement Set

Core Domain Set

Literature review List of candidate M easurement Instruments per Domain document applicability yes For each domain: covered by at least

• ne Instrument?

document applicability

(for each available instrument: is it Truthful, Discriminative and Feasible?)

yes

Candidate Core Outcome M easurement Set

When all Domains have at least one applicable instrument:

consensus

update cycle agreement on how to measure

at least one applicable Instrument per Domain

Core Outcome M easurement Set

Core Domain Set

Literature review List of candidate M easurement Instruments per Domain document applicability yes no develop new Instrument(s)

Preliminary Preliminary Core Outcome

For each domain: covered by at least

• ne Instrument?

consensus

Developing a Core Outcome M easurement Set

document applicability

(for each available instrument: is it Truthful, Discriminative and Feasible?)

no validation studies

ement Set Outcome M easurement Set consensus

Core Domain Set Preliminary Preliminary Core Outcome consensus

Literature review List of candidate M easurement Instruments per Domain document applicability yes no develop new Instrument(s) For each domain: covered by at least

• ne Instrument?

Developing a Core Outcome M easurement Set

Candidate Core Outcome M easurement Set ement Set Outcome M easurement Set consensus consensus

update cycle agreement on how to measure

at least one applicable Instrument per Domain

Core Outcome M easurement Set

When all Domains have at least one applicable instrument: document applicability

(for each available instrument: is it Truthful, Discriminative and Feasible?)

no validation studies

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