# Patient reported outcome measures in spinal muscular atrophy and duchenne muscular dystrophy: review of instruments and their inclusion in clinical and regulatory processes

## TL;DR

This paper reviews how patient and caregiver-reported outcome measures are used in spinal muscular atrophy and Duchenne muscular dystrophy, finding limited and inconsistent use in clinical trials and regulatory processes.

## Contribution

The study systematically evaluates the inclusion of PROMs, ObsROMs, and CROMs in drug development and regulatory assessments for SMA and DMD.

## Key findings

- Only 30% of identified instruments were included in clinical trial protocols, with none as primary endpoints.
- Generic tools like PedsQL are commonly used but lack disease-specific relevance.
- Minimal Clinically Important Difference was reported for just 12% of the instruments.

## Abstract

This study aims to analyze the use of patient-reported outcomes measures (PROMs), observer-reported outcome measures (ObsROMs), and caregiver-reported outcome measures (CROMs) in spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD). The objectives are twofold: (1) to identify and characterize available instruments to be used in research and clinical practice, and (2) to assess their inclusion in drug development and regulatory assessment processes.

A systematic search was conducted using PubMed, Google Scholar, Scopus, and the ePROVIDE database to identify PROMs, ObsROMs, and CROMs for SMA and DMD. The identified instruments were analyzed for validation, psychometric properties, Minimal Clinically Important Difference (MCID), and recall period. Additionally, clinical trial protocols, relative study publications, European Public Assessment Report (EPAR), and Italian Medicines Agency (AIFA) reports for innovativeness recognition on medicines for SMA and DMD (i.e., nusinersen, onasemnogene abeparvovec, risdiplam, and ataluren) were reviewed to evaluate the inclusion of these measures in drug development and regulatory assessment.

The initial search identified 50 questionnaires, including 40 PROMs, 5 ObsROMs, and 5 CROMs. Of these, 15 (30.0%) instruments were included in pivotal clinical trial protocols, with none designated as primary endpoints. Only 6 (12.0%) instruments were mentioned in EPARs, and MCID determination was reported for 6 (12.0%) of the instruments. Generic instruments like the PedsQL were frequently used but criticized for limited specificity.

Despite the availability of PROMs, ObsROMs, and CROMs for SMA and DMD, their use in clinical trials and regulatory documents is limited and inconsistent. Greater standardization and systematic inclusion of these measures are needed to support patient-centered drug development and evaluation.

The online version contains supplementary material available at 10.1007/s10072-025-08600-1.