Systematic evaluation of outcomes is essential for clinical trial research, yet outcomes often neglect the voice of the child and parent, particularly within paediatric orphan diseases.
While guidance for the development and validation of Patient Reported Outcomes (PROs) and Observer Reported Outcomes (ObsRO) measures are available from EMA and FDA , little attention has focused on paediatric and orphan disease PRO/ObsRO development methods[1,2].
We summarize considerations for the development, validation and use of paediatric measures and provide examples of their successful use.
Table 1 provides the recommended steps for PRO/ObsRO development, as well as the challenges and potential solutions in PRO/ObsRO development in paediatrics and orphan diseases. When developing paediatric measures, it is critical to use developmentally appropriate language and techniques to ensure measures have content validity and will be reliable and valid.
Table 1. Challenges and potential solutions for PRO/ObsRO development and implementation in paediatrics and orphan indications
Concept elicitation (using qualitative research) and psychometric validation require samples sizes within narrow age bands (0-2, 3-5, 6-8, 9-11, 12-14, 15-17), but also need to consider rates of development within the context of the condition being studied. From 0-5 years, parents are asked about child behaviours they observe that are indicative of symptoms or impact. For 6-11 years, the child and parent should be asked though simple questions, with images attached to responses, should be used for the child. For 12-17 years, more adult language (without jargon) can be used. Pooling data across ages can only be considered if different age versions are shown to be conceptually equivalent.
PROs have been used to aid decision making for regulatory approval (as in the case of Icatibant for the treatment of Heriditary Angioedema)[3-5] and reimbursement (as in the case of Exjade for the treatment of iron overload for B-thallaesemia and sickle cell disease)[6,7].
Strong paediatric PRO/ObsRO research is needed to ensure ‘fit for purpose’ outcomes are used in paediatric trials to collect robust evidence regarding the safety and efficacy of drugs for children who have orphan diseases. When successfully implemented, all stakeholders benefit: regulators, payers, doctors, parents and most importantly, the children themselves.
Available at http:/ / www.fda.gov/ downloads/ Drugs/ GuidanceComplianceRegulatoryInforma tion/ Guidances/ UCM193282.pdf webciteAccessed January 20, 2012
EMEA: Reflection paper on the regulatory guidance for the use of health-related quality of life (HRQL) measures in the evaluation of medical products. Available at: http://www.ispor.org/workpaper/emea-hrql-guidance.pdf webcite
FDA advisory committee strongly recommends approval and self-administration of FIRAZYR (icatibant) [http:/ / www.fiercebiotech.com/ press-releases/ fda-advisory-committee-strongly-rec ommends-approval-and-self-administr ation] webcite
Fierce Biotech; 2011.
FDA Pulmonary-Allergy Drugs Advisory Committee Meeting Transcripts [http:/ / www.fda.gov/ downloads/ AdvisoryCommittees/ CommitteesMeetingMaterials/ Drugs/ Pulmonary-AllergyDrugsAdvisoryCommi tee/ UCM266639.pdf] webcite
Committee for orphan medicinal products public summary of positive opinion for orphan designation of icatibant acetate for treatment of angioedema [http:/ / www.ema.europa.eu/ docs/ en_GB/ document_library/ Orphan_designation/ 2009/ 11/ WC500006538.pdf] webcite
Cappellini MD, Bejaoui M, Agaoglu L, Porter J, Coates T, Jeng M, et al.: Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with beta-thalassemia.