The utility of central reading of endoscopy examinations in UC is still of unproven value. While it may enhance qualification of a subject into a trial of mild-to-moderate UC population and thereby improving detection of a treatment effect, this potential benefit of central reading has not been shown in trials of moderate-to-severe UC population. Employing central assessment of endoscopic appearance has not been shown to reduce variability. If central reading is recommended it would be important to clarify the overall rationale as to why it is considered valuable. Furthermore, it is important for the agency to provide guidance on the methodology of central reading (including, for example, considerations on single versus multiple central readers and the resolution of discrepancies). It would also be useful to note in the guideline that placebo rates can be high if there is a short wash out prior to the first endoscopy. Clinical response as an endpoint Clinical response would be more appropriate as a meaningful primary endpoint for induction (especially for young people with UC who have failed biologicals) and probably for maintenance also. Biomarkers We agree that biomarkers (such as C-reactive protein and faecal calprotectin) can be helpful indicators of clinical outcome. However, their utility in assessing response to treatment is limited. With regards to the proposed biomarkers, it should be clarified if the proposal is to use biomarkers as a means to enrich the patient population as a companion diagnostic (in which case there should be additional consideration if, for example, inclusion criteria adversely
The utility of central reading of endoscopy examinations in UC is still of unproven value. While it may enhance qualification of a subject into a trial of mild-to-moderate UC population and thereby improving detection of a treatment effect, this potential benefit of central reading has not been shown in trials of moderate-to-severe UC population. Employing central assessment of endoscopic appearance has not been shown to reduce variability. If central reading is recommended it would be important to clarify the overall rationale as to why it is considered valuable. Furthermore, it is important for the agency to provide guidance on the methodology of central reading (including, for example, considerations on single versus multiple central readers and the resolution of discrepancies). It would also be useful to note in the guideline that placebo rates can be high if there is a short wash out prior to the first endoscopy. Clinical response as an endpoint Clinical response would be more appropriate as a meaningful primary endpoint for induction (especially for young people with UC who have failed biologicals) and probably for maintenance also. Biomarkers We agree that biomarkers (such as C-reactive protein and faecal calprotectin) can be helpful indicators of clinical outcome. However, their utility in assessing response to treatment is limited. With regards to the proposed biomarkers, it should be clarified if the proposal is to use biomarkers as a means to enrich the patient population as a companion diagnostic (in which case there should be additional consideration if, for example, inclusion criteria adversely