Ceroid lipofuscinosis neuronal 2 (CLN2) disease, a form of Batten disease, is a rare, degenerative neurometabolic disorder. Disease onset around 2–4 years is followed by rapid decline in motor and neurologic function and mortality in early teenage years (1). Disease burden is best captured using observer-reported outcomes. However, validation is challenging in ultra-orphan diseases, requiring flexible methods and reasonable acceptance of limitations related to participant access.

The study aim was to assess content validation of clinical trial measures (i) CLN2 Disease Based Quality of Life Assessment (Sponsor-developed), (ii) EQ-5D-5L, (iii) Pediatric Quality of Life Inventory (PedsQL); and (iv) PedsQL Family Impact Module.

The Batten Disease Family Association recruited United Kingdom caregivers of a child with CLN2 disease (aged 3–7 years, non-participants in any CLN2 trial), to:

1. 1. Focus groups with symptom elicitation

2. 2. Cognitive interviews to assess measures.

The Focus group comprised eleven caregivers (eight female, three male) from six families. Three families were current caregivers and remainders bereaved. Symptom and disease impact elicited showed the majority of measures domains were relevant.

The interview sample comprised sixteen current caregivers (twelve female, four male) from ten families (caring for eleven children). Overall measures were relevant, easy to understand and answer. However several items were difficult to apply to children with advanced disease (for example, Euroqol, EQ-5D-5L “overall health”), when ability is lost (for example, PedsQL walking), with misinterpretation of “no difficulties” with eating where child feeds using gastrostomy (CLN2 QoL). Caregivers found it difficult to know how their uncommunicative child was feeling (PedsQL worrying, EQ-5D-5L depression). Some symptoms and impacts were missing (for example, constipation, working life).

The mixed-methods approach enabled content validity assessment of multiple measures. While these measures were largely relevant, adjustments could strengthen these for use in this fatal pediatric condition population and increase their acceptance within health technology assessment (HTA).