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Table 1 Descriptive Statistics of the scientific advice (SA)/protocol assistance (PA) procedures in the years 2007 to 2012

From: Adaptive clinical trial designs for European marketing authorization: a survey of scientific advice letters from the European Medicines Agency

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%)