Measuring patient and carer outcomes from genome sequencing for rare disease diagnosis: A critical appraisal of validated outcome measurement instruments and their psychometric properties

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 analyse existing secondary 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

Instruments identified in the systematic literature review that were designed for adult administration were selected for assessment. This list was supplemented with potentially suitable instruments that had not yet been used in this context at the time of the review, identified through hand‑searching and discussions with instrument developers. The selected instruments were evaluated against a pre‑defined set of development and feasibility considerations, followed by an assessment of their psychometric properties informed by the COnsensus‑based Standards for the selection of health Measurement INstruments (COSMIN) methodology.

Preliminary results

This study found that none of the instruments assessed met the COSMIN instrument‑selection guidelines. However, this finding is informed by limited evidence drawn from a small set of psychometric studies and reviewer ratings of content validity. Despite this, a handful of instruments with promising preliminary psychometric evidence were identified. Three GSSIs, four generic multi‑attribute utility instruments (MAUIs), one carer‑specific preference‑based measure (PBM) and one generic psychological instrument were selected for further validation in a longitudinal mixed‑methods multi‑instrument comparison cohort study.

Preliminary conclusions

This study found that further primary research evaluating the content validity (relevance, comprehensiveness, comprehensibility), construct validity (structural validity, convergent/divergent validity, known‑groups validity), responsiveness and feasibility and acceptability of these instruments is needed.