Across 142 Phase III infectious disease CTIS EU submissions, the median end to end review was 93.5 days with an SD of 40.9 days, and 86.6% reached authorization within 120 days. Country specific CTIS Part II review was substantially longer and more variable, with a median of 228 days and an SD of 235.0 days across 327 country decisions. Larger country and site footprints, CRO use, pharmaceutical sponsorship, randomisation, combination treatment, orphan status, HIV, and viral hepatitis aligned with longer timelines.
The end to end timeline was calculated once per trial from initial CTIS submission to first authorization. The median was 93.5 days and the SD was 40.9 days; 53 of 142 trials were authorized within 60 days and 123 of 142 within 120 days.
Only 15.5% cleared within 30 days and 37.3% within 60 days. The authorization curve accelerated after the 90 day point: 47.9% had cleared by day 90, rising to 86.6% by day 120 and 99.3% by day 150.
Across 327 country level observations, CTIS Part II had a median of 228 days and an SD of 235.0 days. Part II is the only country specific timeline in this report; the end to end measure is not assigned to individual countries.
Country Part II was the dominant source of long tail variability. Fewer than one third of country decisions were recorded within 90 days, while 15.3% required more than 540 days.
The Netherlands had the lowest Part II median among countries with repeated observations at 95 days across 17 records. Ireland had the highest median among countries with at least three records at 519 days, while Norway recorded 589 days from one observation.
| Country | n | Median days | SD days | Within 60 | 90 days or longer |
|---|---|---|---|---|---|
| Netherlands | 17 | 95.0 | 188 | 47.1% | 52.9% |
| Bulgaria | 9 | 117.0 | 155 | 33.3% | 66.7% |
| Denmark | 13 | 137.0 | 236 | 46.2% | 53.8% |
| Austria | 12 | 172.5 | 154 | 33.3% | 66.7% |
| Romania | 10 | 189.0 | 177 | 30.0% | 60.0% |
| Portugal | 3 | 199.0 | 439 | 33.3% | 66.7% |
| Hungary | 4 | 200.0 | 295 | 25.0% | 75.0% |
| Slovakia | 4 | 204.5 | 133 | 25.0% | 75.0% |
| Belgium | 25 | 212.0 | 220 | 28.0% | 68.0% |
| Italy | 26 | 217.0 | 247 | 26.9% | 73.1% |
| Estonia | 7 | 224.0 | 169 | 14.3% | 85.7% |
| Spain | 36 | 230.5 | 259 | 25.0% | 66.7% |
| Greece | 8 | 240.0 | 273 | 12.5% | 75.0% |
| Czechia | 7 | 242.0 | 188 | 28.6% | 71.4% |
| Sweden | 9 | 243.0 | 304 | 22.2% | 77.8% |
| France | 66 | 265.0 | 237 | 22.7% | 74.2% |
| Germany | 35 | 270.0 | 244 | 28.6% | 65.7% |
| Lithuania | 2 | 295.5 | 77 | 0.0% | 100.0% |
| Poland | 16 | 322.5 | 250 | 31.2% | 68.8% |
| Finland | 12 | 343.5 | 227 | 33.3% | 66.7% |
| Ireland | 5 | 519.0 | 319 | 20.0% | 80.0% |
| Norway | 1 | 589.0 | n/a | 0.0% | 100.0% |
Country selection materially changes the expected Part II profile. Among the larger country samples, the Netherlands combined the lowest median with 47.1% of decisions within 60 days; France and Germany had medians of 265 and 270 days, while Poland reached 322.5 days.
The number of participating countries had the strongest continuous association with end to end timing among the operational variables tested (Spearman ρ=0.40, p<0.001). Total site count also correlated with longer review (ρ=0.36, p<0.001).
| Footprint | n | Median days | Below median | 90 days or longer |
|---|---|---|---|---|
| 1 country | 93 | 62.0 | 64.5% | 38.7% |
| 2 to 3 countries | 18 | 104.5 | 27.8% | 72.2% |
| 4 to 7 countries | 22 | 110.0 | 27.3% | 72.7% |
| 8 or more countries | 9 | 116.0 | 0.0% | 100.0% |
| 0 to 5 sites | 43 | 53.0 | 74.4% | 27.9% |
| 6 to 20 sites | 51 | 96.0 | 45.1% | 56.9% |
| 21 to 50 sites | 43 | 110.0 | 37.2% | 65.1% |
| 51 or more sites | 4 | 113.0 | 0.0% | 100.0% |
| Country site count | n | Median days | Within 60 | 90 days or longer |
|---|---|---|---|---|
| 0 to 1 site | 51 | 56.0 | 51.0% | 47.1% |
| 2 to 5 sites | 129 | 242.0 | 21.7% | 76.0% |
| 6 to 15 sites | 111 | 254.0 | 24.3% | 71.2% |
| 16 or more sites | 36 | 426.0 | 27.8% | 69.4% |
Single country trials had a 62 day median versus 116 days for trials spanning eight or more countries. Trials with no more than five sites had a 53 day median, compared with 110 days for 21 to 50 sites. Within Part II, countries with zero or one site had a 56 day median, versus 426 days where 16 or more sites were listed.
Seventy one of 142 trials were authorized in less than the 93.5 day median. The strongest descriptive signals were smaller footprints, nonrandomised designs, institutional sponsorship, absence of a CRO, and selected non HIV viral disease groups.
The clearest operational advantage came from limiting scope. Trials with no more than five sites had a 74.4% probability of finishing below the median, and nonrandomised trials had a 72.5% probability. Institutional trials had a 62 day median compared with 109 days for pharmaceutical company sponsored trials.
Overall, 89 of 142 trials (62.7%) required at least 60 days and 74 of 142 (52.1%) required at least 90 days from initial CTIS submission to first authorization. The profiles below had the highest delay rates.
All eight viral hepatitis trials and all nine trials spanning at least eight countries required 90 days or longer. CRO supported trials reached 90 days or longer in 78.6% of cases, orphan trials in 81.8%, HIV trials in 73.7%, and combination trials in 67.3%. These characteristics overlap with larger and more complex multinational programs, so they should be treated as planning signals rather than independent causes.
Submission month showed a visible pooled pattern. May had the lowest median at 52.5 days across 10 trials, followed by October at 61.5 days across 22 and September at 66 days across 21. December had the highest median at 109.5 days across eight trials.
Late spring and early autumn submissions were generally faster in this cohort, but month was less discriminating than country and site footprint. Paediatric status showed almost no separation at 94 versus 93 days, and open label status showed 94 versus 93 days, indicating that neither was a major standalone timing signal.
Calendar days from the initial CTIS EU submission date to the first CTIS authorization date. This is a trial level measure and is not attributed to individual countries.
Calendar days from the earliest recorded Part II submission in a country to the latest recorded decision or authorization in that country.
Sample standard deviation, describing dispersion around the group average. Median is retained as the primary timing statistic because the distributions contain long delays.
Observed differences and rank correlations describe how characteristics moved with review time in this dataset; they do not prove that the characteristic caused the delay.