Title: Parent Reported Quality of Life Measures for Young Children with Primary Ciliary Dyskinesia: QOL-PCD
Funder: Department of Health and Social Care

Abstract: Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disorder that affects approximately 1 in 10-15,000 individuals. Dysfunction of motile cilia, which are responsible to clear airways of mucus and bacteria, causes progressive bronchiectasis. Additional health burdens include persistent rhinitis and impaired hearing. There are no evidence-based guidelines for treatment of PCD; therapeutic strategies are derived from other bronchiectasis-related diseases, particularly cystic fibrosis. This is unsafe because the underlying pathophysiology is different. International networks are collaborating to identify treatments for testing. A major obstacle to evaluating treatments is the lack of disease-specific outcome measures. Patient-reported outcome measures are valid and informative indices of symptoms and functioning, sensitive to patient concerns. We have successfully developed, validated and translated age-appropriate quality of life (QOL) questionnaires- QOL-PCD for the following groups: 6-12years, 13-17years and >18years. There remains a gap for children parent-reported scales have been used in other diseases as a surrogate for patient-reported QOL. Aim Develop and validate parent-reported measures to evaluate QOL of young children with PCD and their parents: QOL-PCDPR Study methods We will replicate methods used to develop and validate our existing measures, following FDA and EMA guidance. We will recruit from the national PCD service. Additionally, recruits from Australia and North America (local funding) will validate the measure to ensure it is cross-culturally equivalent across English speaking countries. Inclusion requires mothers and fathers of children Item generation: Systematic literature reviews and focus groups with PCD professionals have guided the interview proforma. Interviews (face-to-face or telephone) will be audio-typed and analysed to identify key symptoms and psychosocial impacts relevant for this age group. Saturation matrices will ensure saturation is achieved (expected 20-30 interviews). Prototype Questionnaires: Items for the prototype will be determined by frequency of endorsement and level of impact; we will include child-focused and parent-focussed questions. Agreement on item selection and wording will be achieved using modified-Delphi (multidisciplinary and patient representatives). Cognitive interviews with 5-10 parents using a &ldquo;think aloud&rdquo; procedure will evaluate the clarity, interpretation, relevance, and comprehensiveness; a refined draft will undergo validation. Psychometric validation: 82 parents will complete electronic versions of QOL-PCD and generic questionnaires, repeating QOL-PCD after 10-14 days to measure stability. Multi-trait analysis (suitable for low participant numbers in rare diseases) will guide sub-scale development and evaluate construct validity, relating overall score to emerging sub-scales. Convergent and divergent validity will be investigated by correlating sub-scales with the generic questionnaires. The discriminative ability of the scales will be assessed by analysis of variables known to impact QOL (eg. age). Minimal clinically important difference (MCID) will be estimated using distribution-based methods. Expected outputs and impact Based on our existing QOL-PCD measures, we anticipate publications in high impact journals, translation into multiple languages, with rapid uptake by industry and investigators for clinical trials and to monitor clinical progress. We plan for QOL-PCD to be freely available for use in clinics and research within 6 months of the end of the project.

Lay abstract: In the airway, cells are lined with many hair-like structures called cilia that sweep in a coordinated way to clear mucus, bacteria and debris from the lungs, nose and ears. Patients with a rare inherited disease called primary ciliary dyskinesia (PCD), have problems with the movement of the cilia and this results in mucus build-up. They have constant symptoms from birth, which become worse during frequent chest, ear and sinus infections. All children eventually suffer permanent lung damage. We need new treatments to prevent children with PCD from getting infections and to delay lung damage. Also to improve the way children with PCD feel. Researchers are developing new treatments and we now urgently need ways to measure whether these treatments work. Health related quality of life questionnaires provide a way for patients to report changes in their symptoms and well-being when they start a new treatment. Young children may be unable to explain how they feel, so instead we ask parents about how child s symptoms effect daily living, such as sleeping and eating. Asking the parent about how their child s disease effects them at a particular time can help to measure the impact of new treatments. We have already developed QOL questionnaires for older children and adults, which are being used to decide whether treatments work in patients with PCD. We will use this expertise to develop a parent-reported questionnaires for younger children. A researcher will interview parents to understand how PCD impacts their lives; we will then develop a questionnaire for young children with PCD. The questionnaires will be tested by more than 80 parents to ensure it is suitable for deciding whether treatments work in pre-school children with PCD. The study has been developed in collaboration with parents of children with PCD. These parents will continue to support the project, for example by helping design information for families about the study, and ensuring the questionnaire is acceptable for parents of children with PCD. At the end of the study we will ensure that doctors and patients know about these questionnaires so that they will use them. All of the PCD Centres in England are involved in the study, and plan to use the questionnaires in their clinics. We will write reports in medical journals and present talks at international research meetings to ensure clinicians and researchers around the world know about the questionnaires. The research team will show the questionnaires to the UK PCD Support Group on annual Family Days, and will use the support group s social media to ensure families know about the questionnaires.

Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: CONGENITAL DISORDERS