Table 1 Descriptive statistics of the 59 scientific advice (SA)/protocol assistance (PA) procedures in the years 2007–2012 from the initial survey [39] categorised by matching status
Variable | 31 retrieved trials (n (%)) | 28 non-retrieved trials (n (%)) | |
|---|---|---|---|
Type of medicinal product | New chemical entity | 10 (32%) | 13 (46%) |
Known chemical entity | 10 (32%) | 3 (11%) | |
New biological | 9 (29%) | 4 (14%) | |
Known biological | 1 (3%) | 5 (18%) | |
Advanced therapy | 1 (3%) | 3 (11%) | |
Therapeutic area of the indication of the medicinal product | Infectious disorders | 3 (10%) | 1 (4%) |
Oncology | 14 (45%) | 13 (46%) | |
Endocrine and metabolic disorders | 1 (3%) | 2 (7%) | |
Neurologic and psychiatric disorders | 2 (6%) | 1 (4%) | |
Cardiovascular | 5 (16%) | 5 (18%) | |
Diagnostics | 2 (6%) | 4 (14%) | |
Respiratory | 0 (0%) | 1 (4%) | |
Dermatology | 2 (6%) | 1 (4%) | |
Others | 2 (6%) | 0 (0%) | |
Rare disease (prevalence of < 5/10,000) | 21 (68%) | 14 (50%) | |
Applied for orphan designation | 10 (32%) | 11 (39%) | |
Small or medium enterprise | 8 (26%) | 7 (25%) | |
Year when the SA/PA letter was issued | 2007 | 4 (13%) | 3 (11%) |
2008 | 7 (23%) | 2 (7%) | |
2009 | 3 (10%) | 4 (14%) | |
2010 | 7 (23%) | 4 (14%) | |
2011 | 8 (26%) | 10 (36%) | |
2012 | 2 (6%) | 5 (18%) | |
Scale of measurement of the primary endpoint discussed | Time to event | 15 (48%) | 13 (46%) |
Binary | 12 (39%) | 8 (29%) | |
Continuous | 4 (13%) | 7 (25%) | |
Adaptive study is the only pivotal trial | 24 (77%) | 20 (71%) | |
Development phase for which the adaptive clinical trial is proposed | Phase II or IIb | 3 (10%) | 1 (4%) |
Phase II/III | 8 (26%) | 8 (29%) | |
Phase III | 19 (61%) | 19 (68%) | |
Pediatric study | 1 (3%) | 0 (0%) | |
Number of arms of the adaptive trial discussed | 1 | 1 (3%) | 1 (4%) |
2 | 15 (48%) | 19 (68%) | |
3 | 9 (29%) | 6 (21%) | |
> 3 | 6 (19%) | 2 (7%) | |
Stopping for futility was planned for in the adaptive trial | Yes | 17 (55%) | 14 (50%) |
Stopping for efficacy was planned for in the adaptive trial | Yes | 8 (26%) | 11 (39%) |
Number of interim analyses planned in the adaptive trial | 1 | 21 (68%) | 22 (79%) |
2 | 8 (26%) | 5 (18%) | |
> 2 | 2 (6%) | 1 (4%) | |
Type of adaptations planned (multiple answers possible) | Sample size reassessment | 19 (61%) | 24 (86%) |
Population enrichment | 1 (3%) | 4 (14%) | |
Dropping of treatment arms | 13 (42%) | 6 (21%) | |
Other adaptations | 3 (10%) | 1 (4%) | |
CHMP raised issues regarding type I error rate control | 14 (45%) | 5 (18%) | |
Categorisation of the CHMP advice regarding the adaptive study design | Accepted | 7 (23%) | 8 (29%) |
Accepted conditionally (concerns to be addressed) | 17 (55%) | 15 (54%) | |
Not accepted | 7 (23%) | 5 (18%) |