Across 119 Phase III respiratory trials, the median EU CTIS end to end review was 102 days with a population standard deviation of 45.0 days. Only 41.2% reached authorization within 90 days, while 84.9% did so within 120 days. Country specific CTIS Part II review had a lower median of 53 days but a pronounced long tail, and broader country/site scope, CRO involvement and monoclonal antibody programs were the clearest markers of longer timelines.
End to end time, defined as initial CTIS submission to first authorization, ranged from 1 to 231 days. The median was 102 days, the mean was 82.5 days and the interquartile range was 34 to 115 days.
A 90 day planning assumption covered only 49 of 119 submissions. A 120 day assumption covered 101 of 119, making four months the more reliable operational benchmark for Phase III respiratory EU submissions.
Across 427 country review observations, the median CTIS Part II interval was 53 days, but the mean was 182.3 days and the population SD was 219.0 days. The 22.5 to 328.5 day interquartile range shows that country specific Part II timing was strongly right skewed.
The 53 day median is useful for a typical country, but the 219 day SD and 33.7% share beyond 180 days make a single average unsafe for country launch sequencing.
Among countries with at least 10 observations, Denmark had the lowest median at 20.5 days, followed by the Netherlands at 22.5, Czechia at 28.0 and Austria at 29.0. France had the highest median at 142.0 days, followed by Romania at 114.0, Greece at 104.0 and Italy at 98.5.
| Country | n | Median days | SD days | Within 60 d |
|---|---|---|---|---|
| Denmark | 22 | 20.5 | 215.8 | 63.6% |
| Croatia | 3 | 21.0 | 4.1 | 100.0% |
| Netherlands | 24 | 22.5 | 187.8 | 66.7% |
| Latvia | 4 | 26.5 | 7.9 | 100.0% |
| Czechia | 17 | 28.0 | 202.6 | 64.7% |
| Estonia | 5 | 28.0 | 196.4 | 80.0% |
| Austria | 13 | 29.0 | 197.3 | 76.9% |
| Sweden | 12 | 30.0 | 237.3 | 58.3% |
| Finland | 10 | 30.5 | 170.1 | 60.0% |
| Norway | 5 | 31.0 | 231.0 | 60.0% |
| Poland | 31 | 35.0 | 240.5 | 64.5% |
| Ireland | 9 | 38.0 | 182.1 | 77.8% |
| Portugal | 13 | 46.0 | 168.6 | 53.8% |
| Germany | 42 | 49.5 | 188.8 | 50.0% |
| Spain | 42 | 52.5 | 221.6 | 52.4% |
| Belgium | 27 | 55.0 | 230.4 | 51.9% |
| Hungary | 19 | 69.0 | 225.0 | 36.8% |
| Bulgaria | 13 | 92.0 | 251.0 | 38.5% |
| Slovenia | 1 | 98.0 | 0.0 | 0.0% |
| Italy | 30 | 98.5 | 235.7 | 36.7% |
| Greece | 15 | 104.0 | 247.0 | 20.0% |
| Romania | 10 | 114.0 | 203.3 | 20.0% |
| Slovakia | 6 | 141.5 | 111.7 | 50.0% |
| France | 54 | 142.0 | 223.6 | 29.6% |
Country selection materially changes the Part II risk profile. High volume countries ranged from 20.5 to 142.0 median days, a 121.5 day spread before accounting for within country variability.
The number of countries correlated positively with end to end review time (Spearman ρ=0.35, p<0.001), as did total sites (ρ=0.32, p=0.001). Target sample size showed a weaker correlation (ρ=0.19, p=0.044), while planned participant count did not (ρ=0.08, p=0.364).
Coordination breadth was more predictive than enrollment volume. Submissions covering seven or more countries were 32.5 median days slower than submissions covering zero or one country, and large site networks were over ten times as likely to exceed 120 days as the smallest networks.
Excluding months with fewer than five submissions, August had the shortest median at 32.5 days and October followed at 56.5 days. November had the longest median at 125.0 days, with 8 of 12 submissions taking at least 120 days.
Calendar timing was a strong descriptive signal: the November median was 92.5 days longer than August. This pattern should be treated as a planning indicator rather than a causal seasonal effect.
Rare and structural lung disease submissions had the shortest median at 30.0 days, while airway and allergic disease, pulmonary fibrosis/ILD, sleep apnoea/obesity and thoracic oncology all had medians between 109.0 and 112.0 days. Monoclonal antibody only programs had a 115.0 day median versus 96.0 days for small molecule only programs.
| Group | n | Median days | Below median | 120+ days |
|---|---|---|---|---|
| Rare and structural lung disease | 11 | 30.0 | 100.0% | 0.0% |
| Neonatal and prematurity | 5 | 32.0 | 60.0% | 0.0% |
| Critical care and pulmonary vascular | 16 | 70.0 | 56.2% | 25.0% |
| Respiratory infection | 19 | 94.0 | 68.4% | 0.0% |
| Other respiratory | 8 | 107.0 | 50.0% | 25.0% |
| Airway and allergic disease | 37 | 109.0 | 35.1% | 21.6% |
| Pulmonary fibrosis and ILD | 9 | 111.0 | 33.3% | 33.3% |
| Sleep apnoea and obesity | 5 | 112.0 | 0.0% | 20.0% |
| Thoracic oncology | 9 | 112.0 | 33.3% | 22.2% |
| Modality | n | Median days | Below median | 90+ days |
|---|---|---|---|---|
| Other only | 5 | 29.0 | 60.0% | 40.0% |
| Vaccine only | 4 | 85.5 | 75.0% | 50.0% |
| Small molecule only | 55 | 96.0 | 54.5% | 52.7% |
| Mixed modalities | 23 | 102.0 | 47.8% | 65.2% |
| Peptide or protein only | 10 | 104.5 | 50.0% | 60.0% |
| Monoclonal antibody only | 17 | 115.0 | 11.8% | 88.2% |
Modality separated timelines more clearly than combination treatment. Only 2 of 17 monoclonal antibody only trials were below the 102 day median, compared with 30 of 55 small molecule only trials.
Trials with a CRO had a 112.0 day median versus 91.5 days without a CRO. Pharmaceutical company sponsored trials had a 110.0 day median versus 86.5 days for noncommercial or institutional sponsors.
CRO associated trials had 6.2 times the odds of taking at least 120 days compared with trials without a CRO. This is more plausibly a complexity marker than evidence that CRO use itself causes delay.
Open label and blinded trials had similar medians of 100.5 and 103.5 days. Combination and noncombination trials were also similar at 101.5 and 103.0 days. Randomized trials were somewhat slower at 105.0 days versus 87.0 days for nonrandomized trials, but the 120 day delay rate was almost identical at 17.2% versus 16.7%.
Operational footprint, indication and modality separated EU CTIS timelines more strongly than labeling a trial open label, blinded or combination based.
The data support three practical CTIS planning tiers.
End to end means initial CTIS submission to first authorization at trial level. CTIS Part II is country specific and is measured from the earliest Part II submission to the latest country decision or authorization. SD denotes population standard deviation.