OBJECTIVES

To understand how European HTA bodies appraise the applicability of functional measures to assess treatments for Duchenne muscular dystrophy (DMD), Mucopolysaccharidosis type IVa (MPS IVa), and Paediatric-onset hypophosphatasia (HPP).

METHODS

Targeted searches were conducted of publicly available appraisals from the UK (NICE, AWMSG, SMC), Spain (AEMPS), Sweden (SBU, TLV, VGR), Netherlands (ZIN), Germany (G-BA), Italy (AIFA) and France (HAS) for the products Ataluren, Elosulfase alfa and Asfotase alfa treating the above disorders.

RESULTS

The agencies evaluate functional measures differentially and formed different conclusions on their suitability. Six-minute walk test (6MWT) was found to be appropriate by NICE and AEMPS with TLV’s experts indicating that the 6MWT has become an established measure of effectiveness. ZIN also recognised 6MWT as an important outcome measure in MPS IVa and DMD. Although G-BA recognised 6MWT as patient-relevant for both DMD and MPS IVa, it was not considered relevant for HPP.

Three-minute stair climb test (3MSCT) was considered a valid measure in MPS IVa by ZIN but was questioned by G-BA.

Forced Vital Capacity (FVC) as a pulmonary function measure was accepted and considered an important determinant of clinical outcomes for MPS IVa by NICE.

North Star Ambulatory Assessment (NSAA) and Time to Get Up and Stand (TTGUS) or 10-m run are routinely used in clinical practice but considered less relevant than 6MWT in DMD by NICE.

CONCLUSIONS

European HTA bodies view the applicability of these functional measures differently. 6MWT is the most frequently evaluated outcome in these disorders and is a generally accepted measure by the HTA bodies. FVC and other functional measures like 3MSCT, NSAA, TTGUS or 10-m run were also considered applicable but to varying extents. This highlights the variation in HTA bodies opinion and challenges for manufacturers to prepare a single evidence package that can satisfy requirements across them all.