Demonstrating product value from multiple endpoints in rare disease trials

Lionel RIOU FRANÇA, Chief Scientific Officer at Aixial Group, has co-authored an article exploring the application of the win ratio method in Pompe disease.

Rare diseases are often multifaceted, and a single endpoint is often not sufficient to fully describe treatment¹. Demonstrating product benefits for multiple endpoints can however be challenging in small samples as separate testing can lead to a decrease in power. Many methodologies to combine multiple outcomes have their own limitations. Generalized paired comparisons and win statistics address some of these.

The new publication² illustrates the use of one such method, the win ratio, to quantify the benefits of avalglucosidase alfa, in late-onset Pompe disease.

The article can be consulted at: https://ojrd.biomedcentral.com/articles/10.1186/s13023-023-02974-1

1. Verbeeck J, Dirani M, Bauer JW, Hilgers R-D, Molenberghs G, Nabbout R. Composite endpoints, including patient reported outcomes, in rare diseases. Orphanet J Rare Dis. 2023;18:262.
2. Boentert M, Berger KI, Díaz-Manera J, Dimachkie MM, Hamed A, Riou França L, et al. Applying the win ratio method in clinical trials of orphan drugs: an analysis of data from the COMET trial of avalglucosidase alfa in patients with late-onset Pompe disease. Orphanet J Rare Dis. 2024;19:14.

We remain available at Aixial Group to advise you in your evidence synthesis and generation strategies as well as to perform the relevant analyses.