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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

From: Adaptive designs in clinical trials: from scientific advice to marketing authorisation to the European Medicine Agency

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%)