Defining the clinical benefits of disease-modifying therapy in people living with spinal muscular atrophy who require permanent ventilation: a UK-based modified Delphi consensus process

Spinal muscular atrophy (SMA) is a rare inherited neuromuscular disorder that may require permanent ventilation (PV) in severe cases. Although disease-modifying therapies (DMTs) have transformed outcomes for many, prior to this research, access in the UK was restricted for patients receiving PV (SMA-PV). This study aimed to develop consensus recommendations on DMT use and to define clinical benefit in SMA-PV.

A multidisciplinary UK-based expert panel conducted a modified Delphi consensus process between 08 April and 09 June 2025. Draft statements informed by published evidence and expert insights were anonymously voted on for up to three rounds, with consensus defined as ≥75% agreement. Statements not achieving consensus were revised and re-evaluated. Input from a non-voting patient advisory panel (PAP) was also considered. The study was not prospectively registered.

Excluding the Chair, 18 participants evaluated 22 statements across seven thematic areas specific to SMA-PV: DMT access; treatment initiation; treatment monitoring; defining clinical benefit; functional outcomes; quality of life (QoL); and future research priorities. All 22 statements achieved consensus after two voting rounds (100% participation; agreement range 89-100%). Two statements were revised and re-voted in round 2: one after narrowly missing consensus (72% agreement) and the other to incorporate PAP feedback despite achieving 100% agreement in round 1. The panel agreed that PV alone should not preclude access to DMTs and that trial access with personalised treatment goals may be appropriate. The panel also emphasised broader definitions of clinical benefit, including subtle changes in function and QoL, alongside sensitive assessment approaches and harmonised outcome measurement.

These consensus-based recommendations support careful reconsideration of treatment exclusions for patients with SMA-PV and more inclusive, patient-centred approaches to evaluating treatment benefit.

Roche Products Ltd.