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Table 1 Challenges and potential solutions for PRO/ObsRO development and implementation in paediatrics and orphan indications

From: Listening to children’s and parents’ voices: using patient reported outcomes to empower patients with orphan diseases and their parents

Steps to PRO/ObsRO development Challenges Solutions
Literature Review/Desk Research • Literature often limited
• Broad age ranges covered
• Consider grey literature (blogs, dissertations)
• Conduct interviews with expert clinicians, nurses and patient advocacy groups
Concept Elicitation • Limitations in memory, cognitive ability, language by age/condition
• Children can be shy
• Rarity of condition makes recruitment/saturation hard to achieve
• Parents unable to report some symptoms/domains not known to them
• Carefully guided interview guides and well trained interviewers
• Creative interview techniques, toys and drawings
• Collapse age groups where appropriate
• Must achieve saturation within each narrow age range – can this be relaxed for orphan indications? Get FDA feedback early
• Consider other respondents (teachers, nanny etc)
Selection/ development of a measure • Few disease specific measures exist in paediatrics and orphan diseases
• Existing instruments don’t meet FDA/EMA guidance
• Who is the best respondent?
• How should you administer the questionnaire?
• How should the questionnaire be worded?
• Child can’t remember without a concrete event to recall to
• Parent items must be observable….but they may not be with the child all day
• Think about PRO selection early
• Talk to patient advocacy groups
• Engage FDA early
• Consider EPRO vs pen/paper vs IVRS in context of condition and age of child
• Questions/responses should be clear and simply worded
• Short recall period required
• Consider all types of respondents (parent, teacher, nurse, child, dr)
• Consider ‘child told me’ questions
Cognitive debriefing/ content validity testing • Hypothetical situations don’t work with children
• Children give you answers they think you want to hear
• Small sample sizes in rare conditions
• Allow child to complete diaries at home for a few days prior
• Use carefully worded interview guides and well trained interviewers
• Questioning should not be too repetitive nor lengthy
• When analysing, check for consistency between behaviour and responses
• Collapse age groups as appropriate
Psychometric validation • Sample should be stratified by age group, but small samples in orphan indications • Consider validating as part of trial and/or include data from cognitive debriefing (move forward at risk)
• Consider collapsing across age groups
• Consult regulatory early
• Utilize psychometrics done in other diseases if adapting a measure