Across 120 European Phase II respiratory trials, the median end to end EU CTIS submission time was 106 days with an SD of 42.2 days. Country specific CTIS Part II decisions also had a 106 day median, but a much wider 221.8 day SD. Scale was the clearest correlate: one country trials had an 83 day median versus 113 days for trials in seven or more countries.
End to end timing, defined from initial EU CTIS submission to first authorization, had a median of 106 days and an SD of 42.2 days. Country specific Part II timing was measured across 443 country decisions and had the same median but a 221.8 day SD, showing substantially greater country level dispersion.
The typical EU submission reached authorization in roughly three and a half months, but country specific Part II timing was far less predictable than the overall end to end pathway.
Only 39 of 120 trials, or 32.5%, completed end to end EU CTIS review within 90 days. The rate rose to 102 of 120, or 85.0%, within 120 days. Country specific Part II decisions accumulated more slowly after the 106 day median.
For planning, 90 days was achieved by fewer than one third of trials, whereas a 120 day end to end allowance covered 85.0% of EU CTIS submissions.
Croatia had the lowest observed Part II median at 34 days, followed by Latvia at 51.5 days, Austria at 52 days and Portugal at 54 days. Among countries with at least 20 observations, the Netherlands was fastest at 75 days, followed by Belgium at 76 days, Italy at 94 days and Spain at 98 days.
| Country | n | Median days | SD days |
|---|---|---|---|
| Croatia | 2 | 34 | 13 |
| Latvia | 6 | 51.5 | 116.9 |
| Austria | 9 | 52 | 176.3 |
| Portugal | 9 | 54 | 236.8 |
| Netherlands | 31 | 75 | 218.5 |
| Belgium | 25 | 76 | 227.2 |
| Bulgaria | 13 | 91 | 198.9 |
| Italy | 53 | 94 | 235.0 |
| Spain | 53 | 98 | 244.3 |
| Greece | 15 | 99 | 132.8 |
| France | 46 | 100 | 258.6 |
| Poland | 35 | 106 | 193.3 |
| Czechia | 20 | 136 | 216.5 |
| Denmark | 19 | 139 | 215.1 |
| Germany | 52 | 139 | 213.3 |
| Hungary | 14 | 150 | 193.0 |
| Slovakia | 4 | 167 | 100.9 |
| Lithuania | 1 | 208 | 0 |
| Ireland | 9 | 211 | 259.6 |
| Romania | 14 | 212.5 | 166.0 |
| Norway | 5 | 263 | 213.6 |
| Finland | 3 | 335 | 185.0 |
| Sweden | 4 | 339 | 205.4 |
| Estonia | 1 | 564 | 0 |
Country selection materially changes Part II exposure. High SDs in many countries indicate that the median should be used with a contingency buffer rather than as a fixed operational promise.
Number of countries had the strongest continuous association with end to end time, with a Spearman correlation of 0.47. One country trials had an 83 day median and 41.7% reached 90 days or longer; trials in seven or more countries had a 113 day median and 91.3% reached 90 days or longer.
The largest timing penalty appeared when EU CTIS submissions expanded across countries and sites. A staged country strategy is the most direct upstream lever suggested by the dataset.
Pharmaceutical sponsored trials had a 112 day median versus 83 days for academic or healthcare sponsored trials. The commercial group was also larger, with medians of five countries, 17 sites and 120 participants versus one country, four sites and 40 participants, indicating that sponsor type is closely bundled with scale.
| Feature present | Median days | Below median | ≥90 days | Comparison |
|---|---|---|---|---|
| CRO present n=50 |
112 | 30.0% | 88.0% | No CRO: 95 days, 62.9% fast, 54.3% ≥90d (n=70) |
| Digital recruitment n=32 |
113.5 | 31.2% | 90.6% | No digital recruitment: 101 days, 55.7% fast, 60.2% ≥90d (n=88) |
| Randomised design n=66 |
109 | 43.9% | 77.3% | Non-randomised: 99 days, 55.6% fast, 57.4% ≥90d (n=54) |
| Blinded design n=79 |
108 | 45.6% | 74.7% | Open label: 96 days, 56.1% fast, 56.1% ≥90d (n=41) |
CRO use and digital recruitment were associated with longer review, but both occurred in larger, more complex programs. They should be read as complexity markers, not direct causes of regulatory delay.
Lung cancer and thoracic oncology trials had a 94 day median and 51.5% took at least 90 days. COPD and emphysema had a 118 day median and 88.9% took at least 90 days. Small molecule trials were more often faster than the cohort median than antibody based trials, 63.6% versus 27.8%.
| Modality | n | Median days | Below median | ≥90 days |
|---|---|---|---|---|
| Small molecule | 44 | 101 | 63.6% | 59.1% |
| Other modality | 6 | 107.5 | 50.0% | 66.7% |
| Mixed modalities | 37 | 108 | 45.9% | 70.3% |
| Other biologic | 15 | 109 | 40.0% | 80.0% |
| Antibody based | 18 | 111.5 | 27.8% | 77.8% |
The disease and modality signals were smaller than the country and sponsor scale effects. Randomised, blinded and adaptive designs also had higher medians, but their timing differences were consistent with greater program complexity.
September submissions had the lowest median at 39 days, with 73.3% faster than the cohort median and 33.3% taking at least 90 days. October had the highest median among months with at least seven trials at 129 days, while July and December had 100.0% and 92.9% of submissions respectively taking at least 90 days.
| Month | n | Median days | Below median | ≥90 days |
|---|---|---|---|---|
| January | 9 | 73 | 77.8% | 44.4% |
| February | 8 | 107 | 50.0% | 75.0% |
| March | 8 | 111.5 | 25.0% | 87.5% |
| April | 5 | 105 | 60.0% | 60.0% |
| May | 14 | 112 | 21.4% | 85.7% |
| June | 13 | 91 | 61.5% | 53.8% |
| July | 11 | 109 | 36.4% | 100.0% |
| August | 9 | 88 | 88.9% | 44.4% |
| September | 15 | 39 | 73.3% | 33.3% |
| October | 7 | 129 | 14.3% | 85.7% |
| November | 7 | 104 | 57.1% | 57.1% |
| December | 14 | 112 | 28.6% | 92.9% |
Month effects are operationally useful for forecasting but are likely influenced by the mix of countries, sponsors and study designs submitted in each month. They are weaker planning levers than submission scale.
One country submissions had a median of 83 days and 77.1% were faster than 106 days. Academic or healthcare sponsored trials had an 83 day median, and small molecule trials had a 101 day median with 63.6% below the cohort median.
Seven or more countries produced a 113 day median and 91.3% exceeded 90 days. Trials with 31 or more sites had a 111 day median and 95.8% exceeded 90 days. CRO supported trials had an 88.0% 90 day delay rate.
Operational priority: set a 120 day base case for end to end EU CTIS authorization, add country specific Part II contingency, and treat expansion beyond three countries or 30 sites as a material delay risk.