Across 153 Phase III gastroenterology trials, the median end-to-end EU CTIS submission-to-first-authorisation timeline was 83 days (SD 39.5). Country-specific CTIS Part II decisions had a median of 102 days (SD 226.6), with major differences between countries and long right-tail delays. Shorter timelines clustered around May, August and October submissions, single-country footprints, small-molecule programmes and trials without CRO or digital-recruitment infrastructure; mixed modalities and operationally complex programmes had the highest ≥90-day rates.
End-to-end time—initial EU CTIS submission to first CTIS authorisation—was 83 days at the median and 39.5 days by standard deviation. Of 153 trials, 31 (20.3%) were authorised within 30 days, 60 (39.2%) within 60 days, 82 (53.6%) within 90 days and 140 (91.5%) within 120 days.
A 90-day planning assumption covers only 53.6% of Phase III gastroenterology EU submissions. A 120-day regulatory buffer is materially more reliable, covering 91.5%.
Across 595 country-level CTIS Part II decisions, the median was 102 days and the standard deviation was 226.6 days. The distribution was strongly right-skewed: the 25th percentile was 23 days and the 75th percentile was 399.5 days.
Only 47.1% of country-specific Part II decisions were completed within 60 days. The high SD and 399.5-day upper quartile show that country sequencing and long-tail national decisions can materially outlast the first EU authorisation.
Among countries with at least eight observations, Slovakia (24 days), Austria (25), Croatia (28) and Norway (33.5) had the shortest median Part II timelines. France had the longest high-volume median at 214 days, followed by Spain at 147, Bulgaria at 141, Germany at 127.5 and Poland at 120.5 days.
Month was one of the clearest timing signals. May, August and October submissions had a combined median of 40 days; 34 of 53 (64.2%) were faster than the overall median and 18 of 53 (34.0%) required at least 90 days. March, April, September, November and December had a combined median of 106 days; only 18 of 55 (32.7%) were faster than the median and 35 of 55 (63.6%) required at least 90 days.
May, August and October submissions were 1.53 times as likely to finish below the overall median as other months. December had the longest monthly median at 117 days and the highest ≥90-day share at 72.7%.
The number of participating countries—not the total number of sites or participants—showed the clearest trial-footprint association with end-to-end EU CTIS time. Country count had a weak positive correlation with review duration (Spearman ρ=0.17; p=0.035), while total sites had essentially no correlation (ρ=−0.02; p=0.829).
| Group | n | Median | <83 d | ≥90 d |
|---|---|---|---|---|
| 0–1 countries | 86 | 71 | 57.0% | 38.4% |
| 2–6 countries | 28 | 105.5 | 39.3% | 60.7% |
| 7+ countries | 39 | 102 | 41.0% | 56.4% |
| Group | n | Median | <83 d | ≥90 d |
|---|---|---|---|---|
| 0–5 sites | 50 | 87 | 46.0% | 46.0% |
| 6–25 sites | 53 | 77 | 50.9% | 47.2% |
| 26+ sites | 50 | 75 | 52.0% | 48.0% |
Adding countries was more consistently associated with end-to-end delay than adding sites. At national level, however, higher site burden correlated with slower Part II decisions—suggesting that country activation complexity matters after the EU submission enters local review.
Disease-area differences were smaller than modality and design differences. Mixed-modality programmes had a 101.5-day median and 30 of 46 (65.2%) required at least 90 days, versus 68 days and 23 of 59 (39.0%) for small-molecule-only trials. Randomised trials had a 91-day median and 52.7% ≥90-day rate, compared with 70 days and 31.7% for non-randomised trials.
| Disease group | n | Median d | <83 d | ≥90 d |
|---|---|---|---|---|
| Upper GI disease | 7 | 58 | 57.1% | 42.9% |
| GI oncology | 38 | 81 | 50.0% | 44.7% |
| Liver & biliary disease | 29 | 81 | 51.7% | 41.4% |
| Acute/surgical GI | 10 | 84 | 50.0% | 50.0% |
| Inflammatory bowel disease | 52 | 88 | 48.1% | 50.0% |
| Other gastroenterology | 17 | 99 | 47.1% | 52.9% |
| Modality | n | Median d | <83 d | ≥90 d |
|---|---|---|---|---|
| Small molecule | 59 | 68 | 61.0% | 39.0% |
| Monoclonal antibody | 28 | 96 | 46.4% | 50.0% |
| Mixed modalities | 46 | 101.5 | 28.3% | 65.2% |
| Other modality | 11 | 49 | 63.6% | 36.4% |
| Unspecified | 9 | 70 | 77.8% | 11.1% |
Mixed modalities and randomised designs were stronger delay markers than the underlying gastroenterology disease group. Mixed-modality trials were 1.66 times as likely to exceed 90 days as all other modality profiles.
Digital recruitment, CRO involvement and industry sponsorship were the strongest operational associations with ≥90-day EU CTIS review. These characteristics commonly co-occur in larger, multinational and operationally complex programmes, so they should be interpreted as complexity signals rather than causal delay mechanisms.
The most useful planning signal is cumulative complexity. A multinational, randomised, mixed-modality programme using CRO and digital-recruitment infrastructure should be budgeted toward the 90–120+ day range, while simpler single-country submissions are materially more likely to finish below the 83-day median.
End-to-end EU CTIS time: days from initial CTIS submission to first CTIS authorisation at trial level.
CTIS Part II: country-specific days from the earliest Part II submission to the latest national decision or authorisation recorded for that country.
Below median: fewer than 83 end-to-end days.
Substantial delay: at least 60 days; severe delay analysis uses at least 90 days.
SD: standard deviation. RR: unadjusted risk ratio. Associations do not establish causality.