Across 41 Phase I gastroenterology trials submitted through the Clinical Trials Information System (CTIS) in Europe, the trial-level EU submission-to-first-authorisation timeline was a median 89 days (SD 42). Country-specific CTIS Part II was more variable: median 152.5 days (SD 242.3) across 76 country decisions, with country medians ranging from 51 days in Belgium to 506 days in Italy. Smaller geographic footprints and small-molecule-containing programmes aligned with faster review, while multi-country, three-or-more-site, cell-therapy and randomised programmes concentrated more 90-day delays.
The median was 89 days with a 42-day SD, spanning 7 to 194 days. Eleven of 41 trials (26.8%) reached first EU authorisation within 60 days, 22 (53.7%) within 90 days and 34 (82.9%) within 120 days.
A 90-day planning assumption covers only 53.7% of Phase I gastroenterology EU submissions. A 120-day regulatory plan covers 82.9%, while 1 of 41 trials (2.4%) still exceeded 180 days.
Across 76 country-specific Part II decisions, the median was 152.5 days with a 242.3-day SD. Eighteen decisions (23.7%) completed within 30 days, 24 (31.6%) within 60 days and 28 (36.8%) within 90 days; 48 of 76 (63.2%) lasted at least 90 days.
| Country | n | Median and SD |
|---|---|---|
| Belgium | 5 |
51 days
SD 260.0
|
| Denmark | 4 |
53.5 days
SD 281.7
|
| France | 8 |
79 days
SD 251.7
|
| Bulgaria | 2 |
85 days
SD 78.0
|
| Portugal | 3 |
86 days
SD 228.8
|
| Poland | 5 |
128 days
SD 103.3
|
| Romania | 1 |
135 days
SD 0.0
|
| Croatia | 1 |
137 days
SD 0.0
|
| Netherlands | 8 |
151 days
SD 233.5
|
| Sweden | 5 |
163 days
SD 218.6
|
| Germany | 10 |
201 days
SD 257.3
|
| Greece | 2 |
257.5 days
SD 148.5
|
| Ireland | 2 |
282.5 days
SD 257.5
|
| Hungary | 3 |
406 days
SD 131.7
|
| Austria | 1 |
438 days
SD 0.0
|
| Finland | 1 |
461 days
SD 0.0
|
| Spain | 9 |
463 days
SD 276.9
|
| Italy | 6 |
506 days
SD 216.7
|
Among countries with at least three observations, Belgium had the shortest median at 51 days, followed by Denmark at 53.5 and France at 79. Italy had the longest median at 506 days, followed by Spain at 463 and Hungary at 406. Large SDs show that country alone does not fully predict the Part II outcome.
The strongest shorter-than-median signals were a small-molecule-containing programme, a single-country EU submission and a footprint of one or two sites. August submissions also had the shortest descriptive monthly median.
The most actionable upstream choice was submission footprint. The number of countries correlated positively with end-to-end time (Spearman ρ=0.31; p=0.047), while total sites showed a similar relationship (ρ=0.30; p=0.054).
Overall, 30 of 41 trials (73.2%) required at least 60 days and 20 (48.8%) required at least 90 days. The highest 90-day delay rates occurred in multi-country and cell-therapy-containing programmes.
| Attribute | n | Median | ≥60d | ≥90d |
|---|---|---|---|---|
| Multi-country EU submission | 9 | 115d | 8/9 · 88.9% | 7/9 · 77.8% |
| Three or more sites | 14 | 114.5d | 12/14 · 85.7% | 9/14 · 64.3% |
| Cell-therapy-containing | 5 | 105d | 5/5 · 100% | 4/5 · 80.0% |
| Randomised design | 9 | 118d | 7/9 · 77.8% | 6/9 · 66.7% |
| September submission | 7 | 103d | 5/7 · 71.4% | 5/7 · 71.4% |
| December submission | 3 | 121d | 3/3 · 100% | 2/3 · 66.7% |
Geographic complexity was the clearest operational delay signal. Cell therapy and randomisation were directionally slower, but their smaller groups and non-significant timing comparisons mean they should be treated as risk markers rather than deterministic causes.
Without using year as an analytical factor, August had the shortest monthly median at 44 days, followed by February at 53 days. September, November and December had medians of 103, 102 and 121 days, respectively.
The month pattern is useful for contingency planning, not scheduling optimisation: several months had only one or two submissions. The more stable signal was the September group, where 5 of 7 trials (71.4%) reached 90 days or longer.
Participant count was essentially unrelated to end-to-end timing, and CRO presence or adaptive design did not produce a clear acceleration signal.
End-to-end CTIS timeline: initial EU CTIS submission to first CTIS authorisation, calculated once per trial. It is not assigned to individual countries.
CTIS Part II: country-specific interval from earliest Part II submission to the latest recorded national decision or authorisation.
SD: population standard deviation. End-to-end and Part II timelines are separate measures and should not be added together.