European Patients’AcademyonTherapeuticInnovation
Patient-Reported Outcomes (PROs): A patient perspective
Estelle Jobsontoday speaking as EUPATI alumna, patient expert
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European Patients’AcademyonTherapeuticInnovation
§ 11 years as patient advocate (endometriosis)§ 2015-2016, training on medicines R&D for patient
experts with EUPATI (European Patients’ Academy on Therapeutic Innovation)
§ bringing the patient voice§ British Medical Journal (patient peer review & opinion
piece), pharma consulting on communications material with patients, scientific & community advisory board, patient input on R&D application for funding to SNF, engagement with local hospitals (HUG), etc.
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My patient perspective
European Patients’AcademyonTherapeuticInnovation
§ “A PRO is any report of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else.”
§ “A PRO instrument (i.e., a questionnaire) is a means to capture PRO data used to measure treatment benefit or risk in medical product clinical trials.” = PROM
Source: FDA, 2009, Guidance for Industry / Patient-Reported Outcome Measures: Use in Medical Product Development to Support LabelingClaims
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PRO: FDA definitions (2009)
European Patients’AcademyonTherapeuticInnovation
White House meeting about healthcare bill, including women’s health care and maternity services.
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Why do we need patient input?
https://www.bbc.com/news/world-us-canada-39375228
European Patients’AcademyonTherapeuticInnovation
§ Unlike standard clinical outcomes, PROs give us unique insights into how a therapy can affect a patient.
§ Individuals with the exact same health status, diagnosis, or disease may have different perceptions about how they feel and function.
§ Their ability to cope with limitations and disability and other factors can alter perception about satisfaction with life.
§ PRO measures are important as they can lead to a medical science that is more focused on real benefits achievable for the patients.
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PROs are focused on real benefits for the patients
European Patients’AcademyonTherapeuticInnovation
8FDA, proposed areas of patient engagementpresentation at CIOMS meeting, Geneva, April 2019
European Patients’AcademyonTherapeuticInnovation
§ The ability to measure well-being as an outcome becomes especially important in clinical situations where the primary goal of treatment is patient well-being, rather than prolonging life or reducing disease events.
§ For example, patients diagnosed with a chronic disease that is not immediately life-threatening may be most concerned with their emotional state and their ability to live a full life.
§ A patient with a terminal illness may be more concerned with their level of comfort, their ability to live longer, and the impact of their illness on loved ones.
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Measuring well-being?
European Patients’AcademyonTherapeuticInnovation
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Explaining PROs to clinicians
§ Look for existing resources linking researchers and patients? e.g. Canadian Partnership Against Cancer’s Person Centred Perspective: PROs video for clinicians (2’45”)
English: https://youtu.be/AllwTaOr_yw
§ (also in French: https://youtu.be/NEKWhvkGSkA)
European Patients’AcademyonTherapeuticInnovation
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Explaining PROs to patients
§ Person Centred Perspective: PROs video for patients (2’20”) English: https://youtu.be/GtshFS1p70w
(also in French: https://youtu.be/oc4rsojN-Wg)
European Patients’AcademyonTherapeuticInnovation
§ Measures of clinical effectiveness typically reflect outcomes that are important to patients, e.g.:
• symptoms,
• morbidity (incidence/prevalence of disease), or
• mortality.
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Measures of clinical effectiveness
European Patients’AcademyonTherapeuticInnovation
§ e.g. 2014, FDA public meeting with patients who have idiopathic pulmonary fibrosis (IPF), its impact on their daily life, and currently available therapies
§ PROs: major issues associated with uncontrollable, prolonged episodes of coughing: shortness of breath, physical fatigue / overall malaise, and the overall impact on work and home life, including stigma.
§ YET a Delphi panel of 254 medical experts had not indicated coughing as a central symptom.
Source: Morel & Cano, 2017, Orphanet Journal of Rare Diseases, (Table 2). DOI 10.1186/s13023-017-0718-x
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PROs as a missing piece of info
European Patients’AcademyonTherapeuticInnovation§ PROs must be carefully defined so that they capture
information that is important to patients.
§ This information must be measured accurately and as much as possible, in a way that makes it comparable with other measurements.
§ Poor development of concepts will result in the measurement of outcomes that are not important to patients, however accurately measured.
§ Poor measurement methods will identify an outcome that is important to patients, but which is difficult to interpret.
§ PROs = crucial to HTA process + patients actually accessing drug
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How are PROs measured?
European Patients’AcademyonTherapeuticInnovation
See FDA’s draft guidance:
FDA, 2019, Patient-Focused Drug Development: Methods to Identify What Is Important to Patients / Guidance for Industry, Food and Drug Administration Staff, and Other Stakeholders
§ Submit comments by 12/30/2019
www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-focused-drug-development-methods-identify-what-important-patients-guidance-industry-food-and
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Mixed-research methods
European Patients’AcademyonTherapeuticInnovation
Presentation by Dr Thomas Morel at Symposium of SCTO, June 2019
from KU Leuven university hospital, Belgium& Director of Global PROs & Policy, UCB
See Symposium summary report & slides of Dr Morel’s presentation, plus: Article: “Measuring what matters to rare disease patients: Reflections on the work by the IRDiRC taskforce on patient-centered outcome measures”, by Thomas Morel + Stefan Cano, Orphanet Journal of Rare Diseases, 2017https://www.scto.ch/en/event-calendar/symposium/symposium-2019.html
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4 myths about PROs
European Patients’AcademyonTherapeuticInnovation
Myth 1: “All PROs are effectively patient-centred”No. Many “legacy” PROs linger on.Many existing PROs measure what is NOT important to patients (“poor content validity”)Many have “poor face validity” (don’t measure what they claim to measure) and just look like ClinicalROs (clinician-reported outcomes)
Myth 2: “Any validated or published PRO (once it has gotten to label) is acceptable.“ No. Validation is an interactive process, not a status, moreso in rare diseases.The measuring might be statistically ok, but measure meaningless outcomes. What was acceptable for regulators yesterday doesn’t apply to today.
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European Patients’AcademyonTherapeuticInnovation
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4 PRO myths continued…
Myth 3: in clinical research, PROs are merely "nice-to-have” endpoints; No. PROs can measure how patient feels, functions and survives. PROs are crucial, and to all healthcare stakeholders, e.g. HTA / payers, who cannot proceed without them.
Myth 4: “the more the merrier” approach works for PROs.No. Too many PROs kills patient-centredness,making it burdensome for patients to measure. Focus on the key PROs.
European Patients’AcademyonTherapeuticInnovation
§ Article
§ 7 Tables, tangible examples of PRO consultation being used to change R&D
§ A highly useful graphic model of the mechanisms and route of patient input, to guide researchers
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Resource for researchers + patients
European Patients’AcademyonTherapeuticInnovation
Conceptual model
De novo
From an item databank
Personalized outcome measures
Generate items/goals
Cognitive debriefing
Pilottest
Revise PCOM
Identify concepts
Meaningful change
FinalizePCOM
PCOM validation never ends
Understanddisease
PatientsPatient-centered care
Select or adapt
DevelopOther
PsychometricsUse PCOM in patients
Build evidence trailCommunicate externally
QuantitativeQualitativeIterative Milestone
20Source:https://ojrd.biomedcentral.com/articles/10.1186/s13023-017-0718-x
European Patients’AcademyonTherapeuticInnovation
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Practical methods to engage patients
• In-depth pre-trial concept elicitation via patient interviews
• Interviews in a clinical trial setting
• Focus groups• Use of internet and social
media• Direct observation allowing
researchers to ‘shadow’ patients during day-to-day activities
• Audio/written diaries
European Patients’AcademyonTherapeuticInnovation
§ Give patients real examples, e.g. Table 5 (of 7), Duchenne Muscular Dystrophy
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Showcasing the relevance to patients
Diseasecontext: Duchennemusculardystrophy(DMD)usuallypresentsitselfasmuscleweaknessataroundtheageoffourinboys,whichthenrapidlydeteriorates.Typicallymusclelossoccursfirstintheupperlegsandpelvisfollowedbythoseoftheupperarms.Manyareunabletowalkbytheageof12 years.
Drugtrialfocus: Untilrecently,thefocusofdrugtrialsinDMDhasbeentheambulantstageofthedisease.Motorfunctionassessmenthasbeenthemainfocus,withtheuseofthe6-minwalktestandClinROs,suchtheNorthStarAmbulatoryAssessment.
Ashiftinfocus: Sincetheaverageageatlossofambulationisca.10.5 yearsandmediansurvivalis30 years,mostindividualsaffectedbyDMDarenon-ambulant.UndertheleadershipoftheNetherlands-basedadvocacygroupDuchenneParentProject,amultidisciplinaryandmulti-stakeholdergroupidentifiedtheneedfornoveloutcomemeasuresforuseacrossthewholespectrumofDMDpatients.TheydevelopedthePerformanceoftheUpperLimbmodule(PUL),aClinRO designedspecificallyforDMD.
Addingthepatientvoice: InadditiontothePUL,thisgrouprecognised theneedtodevelopinparallelapatient-reportedoutcomemeasuretocomplementinformationondailylivingthatcannototherwisebeobservedinaclinicalorresearchsettingandfocusingonoutcomesthataremeaningfultopatients.AsboysandyoungmenwithDMDwereinterviewedinthatcontext,theyconfirmedthatwhatmatteredtothemincluded: ‘tobeabletoputtheirarmsonthetable’,‘toretaintheabilitytouseacomputerkeyboard’,‘tobrushtheirteeth’,‘topouradrink’etc.– inotherwords,theirhopesfocusedonretainingupperbodyfunction;notnecessarilytoseeimprovementsintheirabilitytowalk.Anexampleofsuchapatientinterview(fortheUpperLimbPRO)isnowavailableonline[86].
European Patients’AcademyonTherapeuticInnovation
§ COS = “sets represent the minimum that should be measured and reported in all clinical trials of a specific condition; applicable for wide range of research skills”
Patient-friendly intro (3’22”) from the COMET (Core Outcome Measures in Effectiveness Trials) Initiative: https://youtu.be/AlLc2yN0pII
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Don’t reinvent the wheel: draw on Core Outcome Sets
European Patients’AcademyonTherapeuticInnovation
§ Searching the COMET database of 300+ sets of already established COShttps://stream.liv.ac.uk/eqyg4t36
§ http://www.comet-initiative.org24
Searching the COMET database
European Patients’AcademyonTherapeuticInnovation
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Working with existing COS + COMET Handbook
TheCOMETHandbook,2017:https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-017-1978-4
European Patients’AcademyonTherapeuticInnovation
before, during, and after PROM development, patients & carers can take part in:• Identifying the need for PROMs,
• Evaluating and reviewing PROMs,
• Developing and evaluating conceptual and/or theoretical frameworks,
• Providing concepts through PRO awareness,
• Endorsing PROMs, and
• Reviewing HTA outputs.Source: Eupati toolbox, creative commons slides and resources www.eupati.eu/clinical-development-and-trials/patient-reported-outcomes-pros-assessment/
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Role of patients / carers / patient organisations
European Patients’AcademyonTherapeuticInnovation
The end / beginning…
… of a more real, useful, beneficial, patient-centred approach to PROs in R&D?
= win-win for:patients, researchers, drs, HTA, payers, regulators & society at large
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