Post on 18-Jan-2022
Pratima Chowdary
Consultant Haematologist
Royal Free Hospital, London
Haemophilia Outcome Measures: A Clinician’s View
European Haemophilia Consortium Round Table of Stakeholders
‘Outcome measures in haemophilia’
28th November 2016
Patient
Outcomes
InnovationIntervention
Comprehensive care
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Haemophilia Care Pathway
Outcome
The way a thing turns out; a consequence
Outcomes measures
‘The determination and evaluation of the results of an activity, plan, process, or program and their comparison with intended or projected results’
Outcome Tools
Measure the outcomes of interest or relevance
Oxford dictionary; www.businessdictionary.com; Developing a Protocol for Observational Comparative Effectiveness Research:
A User’s Guide, Agency for Healthcare Research and Quality (AHRQ) www.ahrq.gov
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Definitions
What / when do we want to measure ?
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Outcomes
Patient
Intervention
Disease
Pathways
• Quantify the effect of treatment / intervention
• Development of disease specific treatment algorithms
• Inform about goal achievement
• Metric for progress
• Guide decision making Patient Service
Society
Developing a Protocol for Observational Comparative Effectiveness Research: A User’s Guide, Agency for Healthcare Research and Quality (AHRQ)
www.ahrq.gov
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Why do we want to measure ?
• Clinical outcomes Biological basis Disease or treatment related
• Humanistic outcomes Patient related
• Health care resource utilisation outcomes Health sector / provider related
• Economic outcomes Society related
Developing a Protocol for Observational Comparative Effectiveness Research: A User’s Guide.
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Outcome Measures – Categories
Example Outcomes in Haemophilia
• Clinical outcomes Mortality Bleed rates
Factor levels including trough level
Inhibitor development Joint arthropathy
• Humanistic outcomes
Health related quality of life
− Generic and disease specific
Pain assessment
• Health care resource utilisation Cost per year
• Economic
QALYS
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Choice of Outcome Measures – Context and Purpose
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Patient Level Stakeholders
Clinicians
Patient
Academia
Group level Stakeholders
Payers
Regulators
Industry
Society
Context & Purpose are Key to the Choice !!
‘Protection’ from
temperature
Intervention
Deaths Deaths
Hypothermia Frost bites
Dehydration Heatstroke
Haemophilia Care – 2016 Context
ENVIRONMENT
• Access to treatment
• Cost of treatment
• Holistic care
TREATMENT
• Increased choice of products
• New targets for treatment
PATIENTS
• Patient compliance
• Good venous access
• Burden of illness
PHYSICIANS
• Variability in physician practices
• No consensus
• Ideal prophylactic regimen
• Good outcomes
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Replace missing factors
Extended half life factors
• Licensed rFVIII
• Elocata
• Adynovate
• Licensed rFIX
• Alprolix
• Indelvion
• To be licensed
• N8 GP & N9 GP
• Bayer PegylatedFVIII
Restoration of thrombin generation
Small molecules
•FVIIIa mimetic
• Emicizumab
•Inhibitors of ‘inhibitors’
• Concizumab
• Fitsuran
•rVIIa
• Albumin fusion rVIIa
• CT Fusion rVIIa
Replace missing gene
Genetherapy
• Bayer & Dimension therapeutics
• Baxalta
• Biomerinux
• Pfizer and Spark therapeutics
• Unicure
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Therapeutic options – Explosion of choices !
• Proof of efficacy for license Regulators
• Treatment benefit Pharmaceutical industry
• Better than before Payer
• ‘Normal life’ and decreased burden of illness and disease Patient
• Markers of treatment response and disease progression Clinician
• Understanding of disease mechanisms Academia and society
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Purpose of outcome measures
• Clinical Baseline assessment
− Starting point before intervention for the ‘problem’ or ‘disease’
Follow-up assessment− Assess change following intervention
Monitoring− Review adherence and potential adverse events
• Care pathway Evaluate if the right people are present at the right time for
right care Impact on clinical outcomes
Resource utilisation
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Outcomes in Clinical Care
• Is the content of the instrument appropriate to the questions that the intervention is intending to address? (Appropriateness/ Relevant)
• Does the instrument produce results that are reproducible and internally consistent? (Reliability)
• Does the instrument measure what it claims to measure? (Validity)
• Does the instrument detect changes over time that matter to patients? (Responsiveness i.e. sensitive to change)
• How precise are the scores of the instrument? (Precision)
• How interpretable are the scores of the instrument? (Interpretability i.e. easy to communicate)
• Is the instrument acceptable to patients? (Acceptability)
• Is the instrument easy to administer and process? (Feasibility)
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Patient Based Outcome Measures - Features
Wade, 1992; Evaluating patient-based outcomemeasures for use in clinical trials, Health Technology Assessment 1998
• ICD-10 (the International Statistical Classification of Diseases and Related Health Problems) Etiological framework for classification by diagnosis
Diseases, disorders and other health conditions.
• ICF (International Classification of Functioning, Disability and Health) Classifies functioning and disability associated with health conditions
Shifts the focus from cause to impact Attempts to place all health conditions on an equal footing Multiple purposes
− Planning
− Policy tool for decision-makers
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WHO Family of Classifications
Towards a Common Language for Functioning, Disability and Health, ICF. WHO Geneva 2002.
ICF Framework
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Health condition (disease or Disorder)
Body structures Activity
Environmental Factors
Personal Factors
Participation
• Bleeding Annualised bleed rate (ABR)
• Musculoskeletal outcome: structure and function Joint health based on physical examination
Imaging
• Musculoskeletal outcome: activities and participation Objective assessment of activities Self-reported assessment of activity and participation
− Disease-specific instruments− Generic instruments
• Parameters for economic evaluation
Fischer et al. Haemophilia 2016
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International Symposium on Outcome Measures in Haemophilic Arthropathy
Zero Annualised Bleed Rate
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Zero ABR - ?
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Maybe
NO
Yes
• Patient groups by outcomes in individualised prophylaxis arm 45% - No bleeds 30% - ABR, 1 to 4.7 25 % - ABR > 4.7
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Annualised Bleed Rate – Pivotal Study
Mahlangu et. al. Blood 2014
Translating Trial Outcomes to Personal Outcomes
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Crux of the problem - Physiological or
Philosophical
Henry Ford “ Change is not
always progress…”
Peter Drucker “Progress is obtained only by
exploiting opportunities…”
Next Steps
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Adding Value
Treatment Algorithms
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‘0’ABR
?
?
Prophylaxis
Replacement therapy
Inte
rve
nti
on
O
utc
om
es
• Patient outcomes
• Treatment outcomes
• Care pathway outcomes
• UK Extended half life (EHL) Outcome Registry Enrol patients being switched to EHLs Gather information about the reasons behind the switch
Monitor patient, disease , treatment and care pathway outcomes
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Patient Registries