Caregiver Versus Investigator Clinical Global Impression-Improvement Ratings In Fenfluramine Clinical Trials

Introduction: In the fenfluramine (FFA) clinical trial program of patients with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), the Clinical Global Impression-Improvement (CGI-I) scale was used to assess change in patients’ conditions relative to baseline. Here, we compare caregiver and investigator CGI-I ratings from the phase 3 and open-label extension (OLE) studies.

Methods: The proportion of patients rated as having clinically meaningful improvement (“much improved” or “very much improved”) at last visit compared to pre-treatment baseline on CGI-I is reported; descriptive statistics were used.

Results: Ratings from 4 randomized controlled trials and 2 OLE studies were included: 2 dosage groups in 3 studies, a subset of adults who enrolled in the DS OLE de novo, and the final DS OLE. In 6/10 assessments, the proportion of investigators who rated patients as having clinically meaningful improvement after FFA was higher vs caregivers. Of the 10 evaluations, median proportions of clinically meaningful improvement ratings were 42.6% (range, 20-64.6) by investigators and 38.1% (range, 27.1-62.5) by caregivers (Figure 1).

Conclusion: In the DS and LGS FFA clinical trials, clinically meaningful improvement ratings on CGI-I were aligned among caregivers and investigators. Caregiver scores likely reflect achievement of goals most important to families and highlight the need to capture both caregiver and investigator CGI-I scores in clinical trials.