with no prior treatment with sodium phenylbutyrate or currently on treatment with sodium phenylbutyrate (Subgroup 1, disease onset after 2 years old; Subgroup 3, disease onset between birth and 2 years old)

previously treated with sodium phenylbutyrate but discontinued treatment due to uncontrolled ammonia level or inability to tolerate sodium phenylbutyrate (Subgroup 2, disease onset after 2 years old; Subgroup 4, disease onset between birth and 2 years old)

Dietary control alone (for Subgroup 2 and Subgroup 4)

Sodium phenylbutyrate (Pheburane; for Subgroup 1 and Subgroup 3)

The model’s main limitations relate to the lack of natural history and treatment progression data presented on UCDs, which led to the use of very uncertain data and of assumptions that were not always appropriately justified. Additionally, the methodological quality of several model elements (such as the correlation of ammonia levels with HAS; the application of liver transplant data; the probabilistic analysis) was poor. However, correcting most of the model flaws that could be fixed does not appear to substantially affect the ICURs, except when varying the simulated relationship between short-term ammonia levels and HAC. When correcting the model methodological flaws and remodelling the relationship between short-term ammonia levels and HAC as appropriately as possible with the data available, results from the probabilistic analysis suggests ICUR for glycerol phenylbutyrate between around $1,000,000 and $2,550,000 per QALY

The manufacturer assumed that patients were treated over a lifetime and that the effect of treatment was maintained during this period. If this maintenance of effect is not accurate, this would have overestimated the ICURs in favour of glycerol phenylbutyrate. In addition, a stopping rule for treatment was not implemented. The direction of the impact of such a rule on the cost-effectiveness results is unknown.