Ethan Basch|Amy P. Abernethy|Bryce B. Reeve
Assuring the Patient Centeredness of Patient-Reported Outcomes: Content Validity in Medical Product Development and Comparative Effectiveness Research
patientreported outcomes pros patient centered patientcentered outcomes patient reported essential characteristic patientcentered approach outcome measurement assesses concepts ie healthrelated phenomena considered important members given target population based direct input representatives population concepts measurement selected based solely convenience interest investigators patientcentered patientreported outcome measures must meet criterion also meaningful comprehensible members population administered including among diverse racialcultural backgrounds lower educationalliteracy levels example pro measure optimally patient centered present pain intensity item mcgill pain questionnaire 1graham c bond gerkovich cook use mcgill pain questionnaire assessment cancer pain replicability consistencypain 1980 8 377387abstract full text pdf pubmed scopus 189 google scholar present pain intensity item used pro measure multiple phase iii clinical trials regulatory context including serving basis us drug approval labeling cancer drug mitoxantrone 1996 2us food drug administrationnovantrone drug labelhttpwwwaccessdatafdagovdrugsatfdadocslabel2009019297s030s031lblpdfgoogle scholar measure however initially developed clinician reporting never underwent qualitative evaluation direct patient input item asks respondents tabled 1how strong pain12345milddiscomfortingdistressinghorribleexcruciating open table new tab response options mix attributes intensity mild bother distressing distinctions options extreme scale clear mild vs discomforting horrible vs excruciating item development direct patient input cognitive interviewing ensure patient understanding would likely yielded different response options limitations highlighted meeting food drug administrations fdas oncology drug advisory committee 2007 3fda office oncology drug products center drug evaluation researchfda expectations endpoint adequacy presentation oncology drugs advisory committee odacwwwfdagovohrmsdocketsac07slides20074309s114fdabaschpptdate july 24 2007google scholar subsequent issuance fdas 2006 draft guidance industry patientreported outcomes measures use medical product development support labeling claims issued final form 2009 4us food drug administrationguidance industry patientreported outcomes measures use medical product development support labeling claimshttpwwwfdagovdownloadsdrugsguidancecomplianceregulatoryinformationguidancesucm193282pdfdate december 2009google scholar subsequently use worst pain item brief pain inventory advocated fda pain intensity assessment regulatory context 5atkinson tm mendoza tr sit l et althe brief pain inventory pain worst last 24 hours item clinical trial endpoint considerationspain med 2010 11 337346crossref pubmed scopus 111 google scholar present pain intensity item developed patientcentered approach ability adequately assess patient pain experience associated disease treatment question viewing concept patient lens patientcentered pro measure must understandable patients variety backgrounds requires direct patient input development revisions contrast measure patient centered without pro example exercise capacity important concept patients selected contexts best evaluated objective approach treadmill test examples highlight importance thoughtfulness selecting developing outcomes use clinical research alluded applies identification concepts evaluated outcomes given context development outcome measures assessing concepts twopart article content validity issue value health 6patrick dl burke lb gwaltney cj et alcontent validityestablishing reporting evidence newlydeveloped patientreported outcomes pro instruments medical product evaluation ispor pro good research practices task force report part 1eliciting concepts new pro instrumentvalue health 2011 14 967977abstract full text full text pdf pubmed scopus 485 google scholar 7patrick dl burke lb gwaltney cj et alcontent validityestablishing reporting evidence newlydeveloped patientreported outcomes pro instruments medical product evaluation ispor pro good research practices task force report part 2assessing respondent understandingvalue health 2011 14 978988abstract full text full text pdf pubmed scopus 493 google scholar provides important contribution methodological literature complements fdas pro guidance toward standardizing methods development endpoint models pro instruments optimally patient centered key message article importance directly eliciting patient perspective qualitative research identification concepts evaluated whether patient reported developmentrefinement pro measures critiques fdas pro guidance setting high methodological bar sponsors attain approach content validity overly focused qualitative quantitative methods 8magasi ryan g revicki et al content validity patientreported outcome measures perspectives promis meeting qual life res pressgoogle scholar truth assertions overall impact fdas emphasis qualitative methods positive leading investigators regulatory nonregulatory spaces focus patient perspective thus creating need blueprint provided twopart article issue potential limitation methods described twopart article reliance good faith judgment investigators interpreting qualitative data decide concepts appropriate measure given context risk investigators select concepts measurement cast particular product positive light ignoring concepts could appear less favorable example product reduces pain increases nausea investigators could choose evaluate former although important patients misuse regulatory tenet fitforuse endpoint design risks conveying incomplete picture impact treatment patients subjective experience fact part one article discussion titled understand disease condition target population acknowledged selection outcomes appropriate given trial program often informed consultation clinical trial design measurement experts well extensive literature review therefore key item investigators developing new pro measure selecting existing measure use new study 1 describe concepts reported important patients target population closely related population 2 provide rationale concepts included excluded recommendations twopart article largely apply regulatory context largely us regulatory context apply comparative effectiveness research cer prospective cer controlled clinical studies recommendations taken virtually intact particular emphasis developing conceptual frameworks relationships various outcomesas elegantly shown psoriasis figure 1 part one article fit purpose focus regulatory setting less applicable cer approaches registries longitudinal observational studies often exploratory nature instances inclusion broader selection outcomes intended signal generation beyond initial qualitative work merited example multiitem symptom healthrelated qualityoflife battery appropriate addition measurement contextspecific concepts interest regardless upfront qualitative research identify salient concepts prior conducting type prospective clinical cer strongly recommended critical remember research inform care patientsand understood interpreted patientsis one targets cer hence patientcentered pro measures need consistently understandable meaningful patients generally requires patient input front notably additional qualitative evaluations patients completing quantitative psychometric studies also informative example psychometric analysis patientreported measure item response bias could detected ie differential item functioning hispanic nonhispanic patients statistical tools identify differential item functioning requires qualitative work illuminate underlying drivers differences qualitative methods also incorporated prospective clinical research provide insights patient perspectives key time points relationships outcomes interventions measure developed periodically reevaluated treatment paradigms patient perspectives shift time ensure remains appropriate representative meaningful concepts noted twopart article central importance conducting qualitative evaluations establishing content validity regulatory cer environments inclusion heterogeneous sample within target population addition including representatives various racialcultural applicable linguistic backgrounds diverse educationalliteracy levels included moreover methodological expertise analyze data adjust verbiage accordingly recommended patients higher educational levels easier identify recruit clinical research therefore efforts must made include hardtoreach individuals example requirement development work two us national institutes health initiatives patientreported outcomes measurement information system promis patientreported outcomes version common terminology criteria adverse events proctcae include cognitive interviews among patients low education levels eg 12 years education measured reading level ninth grade using wide range achievement test3 reading subtest 9dewalt da rothrock n yount stone promis cooperative groupevaluation item candidatesthe promis qualitative item reviewmed care 2007 45 s12s21crossref pubmed scopus 460 google scholar 10hay j atkinson tm mendoza tr et alrefinement patientreported outcomes version common terminology criteria adverse events proctcae via cognitive interviewingj clin oncol 2010 28 abstr 9060 15spubmed google scholar summary qualitative research essential identifying concepts measurement given target population refining measures assess concepts continued assurance concepts measures remain appropriate meaningful time work include hardtoreach patients particularly diverse racialcultural educationalliteracy levels approach applies trials regulatory context prospective clinical cer beginning process early possible given research program afford opportunity develop select appropriate concepts measures optimally patient centered source financial support authors financial relationships disclose