Evaluating the content validity, construct validity, responsiveness, interpretability, feasibility, and acceptability of outcome measurement instruments in the context of genome sequencing for rare disease diagnosis: A longitudinal mixed-methods multi-instrument comparison study

Background

Rare diseases (RDs), such as Angelman syndrome and retinitis pigmentosa, are individually rare yet collectively affect 6–8% of the general population. Diagnosis can take years and often requires many costly investigations. Genome sequencing (GS) is improving both RD diagnostic yield and diagnostic speed. However, the information uncovered is complex and can impact patients and informal carers across clinical, emotional, cognitive, behavioural and social outcomes. Previous approaches to measuring these outcomes have been inconsistent, with limited psychometric evidence available to inform instrument selection in this context.

Aims

This study aimed to collect and analyse new primary data to determine the most suitable patient‑ and carer‑reported outcome measurement instruments for measuring outcomes of GS for RD diagnosis in economic evaluations.

Methods

Adults undergoing GS for RD diagnosis, and informal carers of children and adults undergoing sequencing, were recruited from three United Kingdom (UK) National Health Service (NHS) Genomic Medicine Services (GMS) over a 12‑month period. Participants completed surveys at baseline and at six months, and a subset were interviewed. Participants were asked to complete and provide feedback on generic multi‑attribute utility instruments (MAUIs) and GS‑specific instruments. Content, structural, discriminative and longitudinal validity, as well as feasibility and acceptability, are being assessed.

Preliminary results

A large sample of 324 participants was recruited (104% of target) and completed the baseline survey, including 152 adults and 172 carers. Of these, 220 (67.9%) participants completed the follow‑up survey, and 30 were interviewed. Analysis is ongoing.

Preliminary conclusions

This study found that generic MAUIs demonstrate insufficient psychometric performance for measuring outcomes in this context. Failure to account for the full impact of GS in economic evaluations may result in under‑ or over‑utilisation, leading to inefficiencies such as delayed diagnosis, unnecessary testing and undue burden on patients and carers. This may, in turn, reduce the funds available to cover other health system costs.