Table 1 Descriptive Statistics of the scientific advice (SA)/protocol assistance (PA) procedures in the years 2007 to 2012
Variable | N (%) | |
|---|---|---|
Number of SA/PA letters with questions on adaptive phase II, phase II/III or phase III designs | 59 (100%) | |
Type of medicinal product | New chemical entity | 23 (39%) |
Known chemical entity | 13 (22%) | |
New biological | 13 (22%) | |
Known biological | 6 (10%) | |
Advanced therapy | 4 (7%) | |
Therapeutic area of the indication of the medicinal product | Infectious disorders | 4 (7%) |
Oncology | 27 (46%) | |
Endocrine and metabolic disorders | 3 (5%) | |
Neurologic and psychiatric disorders | 3 (5%) | |
Cardiovascular | 6 (10%) | |
Diagnostics | 1 (2%) | |
Respiratory | 3 (5%) | |
Dermatology | 2 (3%) | |
Others | 10 (17%) | |
Rare disease (prevalence of <5/10,000) | 35 (59%) | |
Applied for orphan designation | 21 (36%) | |
Small or medium enterprise | 15 (25%) | |
Year when the SA/PA letter was issued | 2007 | 7 (12%) |
2008 | 11 (19%) | |
2009 | 8 (14%) | |
2010 | 10 (17%) | |
2011 | 16 (27%) | |
2012 | 7 (12%) | |
Scale of measurement of the primary endpoint discussed | Time to event | 28 (47%) |
Binary | 20 (34%) | |
Continuous | 11 (19%) | |
Adaptive study is the only pivotal trial | 44 (75%) | |
Development phase for which the adaptive clinical trial is proposed | Phase II or IIb | 4 (7%) |
Phase II/III | 16 (27%) | |
Phase III | 38 (64%) | |
Pediatric study | 1 (2%) | |
Number of arms of the adaptive trial discussed | 1 | 2 (3%) |
2 | 34 (58%) | |
3 | 15 (25%) | |
>3 | 8 (14%) | |
Stopping for futility was planned for in the adaptive trial | Yes | 31 (53%) |
Stopping for efficacy was planned for in the adaptive trial | Yes | 19 (32%) |
Number of interim analyses planned in the adaptive trial | 1 | 43 (73%) |
2 | 13 (22%) | |
>2 | 3 (5%) | |
Type of adaptations planned (multiple answers possible) | Sample size reassessment | 43 (73%) |
Population enrichment | 5 (8%) | |
Dropping of treatment arms | 19 (32%) | |
Other adaptations | 4 (7%) | |
CHMP raised issues regarding type I error rate control | 19 (32%) | |
Categorization of the CHMP advice regarding the adaptive study design | Accepted | 15 (25%) |
Accepted conditionally (concerns to be addressed) | 32 (54%) | |
Not accepted | 12 (20%) |