the patient reported outcomes, burdens, and experiences...

The Patient Reported Outcomes, Burdens, and Experiences (PROBE) Study

Phase 1 Methodology and Feasibility

Enhancing the Direct Patient Voice in Health care Decision Making

HTAi2016AnnualMeeting13May2016– Tokyo,Japan

©2016PatientOutcomesResearchGroupLtd

Enhancing the direct patient voice in healthcare decision-making.©2016PatientOutcomesResearchGroupLtd

What is Hemophilia?

• Incidence 1 in 10,000 (X-linked recessive)• Deficiency of clotting factor protein• Blood does not clot properly• Severe patients (<1% clotting factor) at most risk

• Clinical manifestations• Internal bleeding into joints, soft tissues• Significant morbidity and mortality

• SOA treatment (There is no cure, at least yet)• Prophylaxis (factor concentrate replacement)• Integrated disease management


Answering Unanswered Questions

• World Federation of Hemophilia (WFH) Global Survey shows:• DX: How many PWH are diagnosed (prevalence vs expected incidence)• TX: How much treatment is available (per capita or for a typical PWH)• Mortality: If PWH are surviving into adulthood (ratio children : adults)

• What we don’t understand well is how the typical PWH is fairing in their daily life (Quality of life)• How are various dimensions of living impacted?• What interventions influence them?

The goal of treatment is not simply to add years to a PWH’s life, but to add life to their years!


Increasing the Value of the Patient Voice

• Moving advocacy arguments beyond emotion and anecdote to evidence-based arguments grounded in real-world patient outcomes• Providing a validated foundation for decision making in Health

Technology Assessments and comparative effectiveness research• Raising awareness of the impact of living with hemophilia,

treatment and effective prevention from the patient perspective

Patients have a unique perspective and consider issues differently than regulators, manufacturers, scientists, clinicians and payers.


Gather & Interpret Patient-Centered Experiential Data

Evidence-based arguments grounded in real-world patient experiences


Multi-phase Project

• Phase 1 (2014-2015) – Feasibility assessment• Develop / Test understanding of questionnaire content and clarity• Assess methodology and in-country implementation feasibility• Establish core analytics

• Phase 2 (2016) – Reproducibility assessment• Pilot web platform• Validate reproducibility (individual and population level)• Establish analytic controls / population comparators

• Phase 3 (2017-beyond) – Global Implementation


Deliverables• A self-reported outcomes data framework with metrics to:• Perform reliable assessments

• Within a country or between countries over time

• To the general population and other diseases

• Easy to administer, low resource burden, global• Usable by patient organizations worldwide (multi-lingual)

• Both paper (Phase 1) and web-based (Phase 2)

• Designed to complement and enhance the utility of national patient registries and the WFH Global Survey


Participating Countries – Phase 1 Feasibility Assessment

Argentina (Cordoba Chapter), Australia, Brazil, Canada, France, Germany, Hungary, Ireland, Italy, Japan, Mexico, Netherlands, New Zealand, Spain, United Kingdom, United States, and Venezuela


Results – Phase 1 Feasibility Assessment

• Field work complete 704 responses (117% of objective) • 379 FVIII PWH, 86 FIX PWH, • 212 not affected by a bleeding disorder• 27 other / unknown bleeding disorder

• Preliminary analysis indicates study methodology is feasible• 71.3% met study objectives as to time to completion (0-15 min)

• Minimal to acceptable staff time required• For one cycle of administration: 2 - 40 hours (median 9 hours)


Patient-Centered Outcomes

• On patients: Directly probe outcomes relevant to patients’ life• Impact on daily living – pain, independence, educational attainment,

employment, family life, mobility, …• Current health status (EQ-5D-5L – VAS)• Demographics

• On healthy “controls”: Build a benchmark comparator• Applicable questions asked also to non-hemophilia subjects

• On patients, it also collects explanatory variables:• Treatment history – disease severity, treatment regimen, bleeds, joint

impairment / interventions, …


The “Concept” of Comparison

Dimension Country Control Mild Mod Severe

EQ5D-5L A (some prophylaxis) .897 .788 .788 .676B (no prophylaxis) .894 .788 .801 .590

-.086Chronic pain A (some prophylaxis) 28% 53% 68% 78%

B (no prophylaxis) 30% 56% 70% 86%+56%

PROBE Investigators unpublished data not for citation


Preliminary Observations

• Preliminary data analysis also indicates variable correlation between patient responses to PROBE study questions using standardized clinical definitions when compared with responses to questions using patient-developed definitions. • The variation highlights the importance of continued research to

assess whether clinical trial end-points are the appropriate measures to evaluate real-world patient outcomes.


AcknowledgmentsInvestigatorsPrincipal Investigator• Mark Skinner JD, Institute for Policy

Advancement Ltd. (US)Co-Investigators:• Randall Curtis MBA, Factor VIII

Computing (US) • Neil Frick MS, National Hemophilia

Foundation (US) • Alfonso Iorio MD Ph.D. FRCPC, McMaster

University, Department of Clinical Epidemiology and Biostatistics (Canada)

• Michael Nichol Ph.D., University of Southern California, School of Policy and Planning Development (US)

• Declan Noone, Irish Haemophilia Society (Ireland)

• Brian O’Mahony, Irish Haemophilia Society, Trinity College Dublin (Ireland)

• David Page, Canadian Hemophilia Society (Canada)

• Jeff Stonebraker Ph.D., North Carolina State University, Poole College of Management (US)

FundersPROBE is an independent investigator led research project supported with unrestricted grants from: • Baxalta USA Inc.• Bayer Healthcare• Biogen• Novo Nordisk HERO• Sobi

Administrative support provided by the US National Hemophilia Foundation

Collaborating Patient Organizations• Fundación de la Hemofilia (Argentina)

Cordoba Chapter• Hemophilia Foundation Australia• Federaçao Brasileira de Hemofilia (Brazil)

• Canadian Hemophilia Society• Association Française des Hémophiles

(France)• Deutsche Hämophiliegesellschaft

(Germany)• Magyar Hemofilia Egyesulet (Hungary),

Irish Haemophilia Society• Federazione delle Associazioni Emofilici

(Italy)• National Hemophilia Network of Japan• Federación de Hemofilia de la República

Mexicana (Mexico)• Nederlandse Vereniging van Hemofilie-

Patiënten (The Netherlands)• Haemophilia Foundation of New Zealand, • Federación Española de Hemofilia (Spain • The Haemophilia Society (United

Kingdom)• National Hemophilia Foundation (US)• Asociación Venezolana para la Hemofilia

(Venezuela)


For More Information

If you have questions or would like more information about PROBE you may directly contact the PROBE investigator team:• Mark W. Skinner, Principal Investigator• E-mail: [email protected] • Phone: +1-202-253-8342• Web: www.probestudy.org

the patient reported outcomes, burdens, and experiences...

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