Across 34 Phase I respiratory trials, the median EU CTIS submission to first authorization time was 111 days. Country specific Part II review had a 60.5 day median, but its 245.9 day SD shows a pronounced long tail. Larger multicountry and multisite submissions, first in human programs, combination regimens, and adaptive or escalation designs were the clearest correlates of longer review.
End to end review is measured from the initial EU CTIS submission to the first authorization. Part II is measured separately at country level and is not assigned to an individual country as an end to end metric.
The EU end to end distribution is concentrated near four months, whereas Part II has a much wider country specific tail. The median is therefore more representative than the Part II mean.
Only 1 of 34 trials (2.9%) reached first EU authorization within 30 days, while 28 of 34 (82.4%) did so within 120 days. Part II reached 50.0% within 60 days but then accumulated slowly because of the long country tail.
A 120 day planning assumption captures 82.4% of first EU authorizations, but only 57.6% of country Part II decisions. Operational plans requiring all selected countries should therefore use country specific benchmarks rather than the EU first authorization median alone.
Denmark had the lowest country median at 12 days across 3 observations. Among countries with at least 6 observations, the median ranged from 31 days in the Netherlands to 284 days in Belgium. End to end timing is intentionally not shown by country because it is an EU submission level measure.
| Country | n | Median days | SD | Relative median |
|---|---|---|---|---|
| Denmark | 3 | 12.0 | 41.0 | |
| Ireland | 3 | 25.0 | 242.8 | |
| Austria | 3 | 26.0 | 259.8 | |
| Sweden | 2 | 28.0 | 17.0 | |
| Czechia | 3 | 29.0 | 10.4 | |
| Latvia | 1 | 29.0 | 0.0 | |
| Netherlands | 9 | 31.0 | 204.1 | |
| Poland | 7 | 38.0 | 182.4 | |
| Italy | 8 | 58.5 | 256.0 | |
| Spain | 13 | 61.0 | 273.1 | |
| Portugal | 4 | 70.0 | 205.7 | |
| Greece | 2 | 91.0 | 8.0 | |
| France | 9 | 191.0 | 270.0 | |
| Romania | 2 | 207.0 | 107.0 | |
| Germany | 15 | 231.0 | 271.9 | |
| Belgium | 6 | 284.0 | 229.3 | |
| Finland | 1 | 461.0 | 0.0 | |
| Bulgaria | 1 | 532.0 | 0.0 |
Country choice is a major source of Part II variability. Germany, France, Belgium and several smaller cohorts show both high medians and high SD, indicating that predictability is as important as the point estimate when selecting countries.
Country count and site count each had a moderate positive correlation with EU review time. Single country and 1 to 3 site trials had an 83 day median; every trial with 4 or more sites took at least 90 days.
Scale was the most consistent measurable correlate. Among 17 single country trials, 13 (76.5%) were faster than the 111 day median; among 17 trials with more than one country, only 4 (23.5%) were faster.
Without using year as an analytical factor, submissions made from July through September had the shortest median at 74 days, and all 5 were faster than the overall median. October through December submissions had a 114 day median and 5 of 12 (41.7%) reached 120 days or longer.
The summer submission window was associated with shorter review in this cohort, while late calendar submissions carried the largest 120 day delay rate. The July to September group is small, so this should be treated as a planning signal rather than a deterministic rule.
First in human, combination, and adaptive or escalation programs were more frequently in the 90 day or longer group. Randomisation alone showed a smaller difference.
All 5 first in human trials took at least 90 days. Combination trials had an 113 day median versus 93 days for single treatment trials, and adaptive or escalation designs had a 91.7% 90 day delay rate versus 54.5% for non adaptive designs.
Airway and inflammatory programs had the shortest disease group median at 87 days. Thoracic oncology had a 112 day median and 11 of 13 trials (84.6%) took at least 90 days. Respiratory infection trials had a 115 day median, although only 3 trials were included.
Airway focused Phase I programs were more often below the cohort median, while oncology and infection programs more often crossed 90 days. Much of this difference overlaps with scale, combination treatment and adaptive design.
The faster half of the cohort was operationally compact. The 90 day or longer group was more multinational, more multisite and more likely to combine therapies or use early phase adaptive features.
For planning, the most defensible fast profile is a single country, 1 to 3 site, non first in human submission without a combination regimen. Multicountry expansion and complex early phase design should be budgeted near or above the 111 day median, with country specific Part II contingencies.