Patient-Reported Outcomes (PROs): A patient perspective › unibe › portal › fak_medizin › ... · Patient-Reported Outcomes (PROs): A patient perspective Estelle Jobson today

European Patients’AcademyonTherapeuticInnovation

Patient-Reported Outcomes (PROs): A patient perspective

Estelle Jobsontoday speaking as EUPATI alumna, patient expert

[email protected]

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§ 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


§ “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)


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


§ 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


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PRO input is right at the beginning


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EUPATI proposed areas of patient engagement


8FDA, proposed areas of patient engagementpresentation at CIOMS meeting, Geneva, April 2019


§ 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?


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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)


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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)


§ 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


§ 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?


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


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


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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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.


§ 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


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


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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


§ 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].


§ 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


§ 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


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Working with existing COS + COMET Handbook

TheCOMETHandbook,2017:https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-017-1978-4


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


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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§ Thank you for your attention. § Meanwhile, at today’s meeting on feline healthcare…

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Patient-Reported Outcomes (PROs): A patient perspective › unibe › portal › fak_medizin › ... · Patient-Reported Outcomes (PROs): A patient perspective Estelle Jobson today