Patient-reported outcomes validated in phase 3 clinical trials: a targeted literature review

Regulatory guidance advises validation of patient-reported outcome (PRO) instruments prior to use in pivotal clinical studies, which may then be used to generate critical patient-centered evidence and support labelling claims. This targeted literature review aimed to determine if PRO instruments psychometrically validated in a phase 3 trial setting could support label claims from the same phase 3 study (i.e. PRO data were generated as an endpoint).

A targeted search of published studies (1 January 2006-3 June 2021) using the MEDLINE database identified PRO instruments validated during phase 3 trials. The search included instrument terms (e.g. patient-reported outcome measures, questionnaire, survey) and validation terms (e.g. reproducibility, minimal important difference), without filtering for therapeutic indications. Results were limited to phase 3 clinical trials or validation studies. The PROLABELS database was used to identify PROs validated in phase 3 trials and accepted in labelling claims.

Of 355 references identified, 68 studies with PRO psychometric validation in phase 3 studies were selected, covering 78 instruments. Of these, 20 were novel PRO instruments and 58 were existing instruments being validated for a new therapeutic indication/population. The psychometric properties most frequently validated were internal consistency reliability, known-group validity, responsiveness, minimal important difference, and concurrent validity. Five novel instruments obtained ten labelling claims for seven drugs/products.

These results suggest that quantitative validation of novel PRO instruments, and existing PROs for new indications, can occur within the context of phase 3 trials, and these PROs can also support label claims.