COSCIENS Biopharma Inc T.CSCI

Perplexity Ai:

[prophetoffactz]

Based on the information provided, there is a strong case for the FDA to consider accepting a higher cut-off point for the macimorelin test in diagnosing growth hormone deficiency (GHD), particularly in the pediatric population. Here's why:

1. Increased sensitivity: Using a higher cut-off point of 5.1 ng/mL for macimorelin increased the sensitivity to 92% while maintaining a high specificity of 96%. This suggests that a higher cut-off would reduce the risk of missing true cases of GHD.
2. Better agreement with ITT: Post-hoc analysis showed that using 5.1 ng/mL for both macimorelin and the insulin tolerance test (ITT) improved positive agreement from 74% to 82%, while maintaining a high negative agreement of 94%. This indicates better overall concordance with the gold standard ITT at the higher cut-off.
3. Robust performance: The diagnostic performance of macimorelin was not significantly affected by age, BMI, or sex. This suggests that adjusting the cut-off would likely maintain its reliability across different patient groups.
4. Safety and convenience: Macimorelin has shown a more favorable safety profile and is more convenient than the ITT. Accepting a higher cut-off that improves its diagnostic accuracy would leverage these advantages.
5. Unexpected pediatric results: The recent pediatric trial showed unexpectedly high growth hormone production with macimorelin, suggesting that children may be more sensitive to its effects. This supports the need for a higher cut-off specific to the pediatric population.
6. Potential false positives in other tests: The pediatric trial results hint at the possibility that other tests (arginine and clonidine) may be producing false positives. A higher macimorelin cut-off could help differentiate true GHD cases more accurately.

While more analysis is needed, especially for the pediatric population, the existing data suggests that accepting a higher cut-off for macimorelin could improve its diagnostic accuracy without compromising specificity. This would allow for better identification of patients who truly need growth hormone treatment while maintaining the test's other advantages in safety and convenience.