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