Across 186 Phase II or Phase II inclusive cell therapy trials submitted through the European Union Clinical Trials Information System (CTIS), the median end-to-end review was 55.5 days (SD 48.6). Country-specific CTIS Part II decisions were much more dispersed: 323 country-trial records had a median of 238 days (SD 227.8). Submission month and operational scale were the clearest correlates of speed: August–October submissions had a 29-day median, while trials in four or more countries had a 115.5-day median.
The trial-level end-to-end metric reached its midpoint at 55.5 days, whereas the country-specific Part II metric reached its midpoint at 238 days. End-to-end timing is therefore reported once for the EU submission and is not attributed to individual countries.
Median from initial CTIS submission to first authorization across 186 trials. Mean 68.4 days; SD 48.6; range 1–194 days.
Median from earliest country Part II submission to the latest country decision or authorization across 323 records. Mean 277.0 days; SD 227.8; range 2–777 days.
The central EU CTIS decision occurred in roughly two months for half of trials, but country-level Part II records were far more variable. Operational planning should therefore separate the EU end-to-end milestone from country activation readiness.
For end-to-end review, 95 of 186 trials (51.1%) were authorized within 60 days and 110 (59.1%) within 90 days. For Part II, 162 of 323 country records (50.2%) concluded within 240 days, closely matching the 238-day median.
A 60-day planning assumption describes the median end-to-end EU submission, but not country Part II. Only 102 of 323 Part II records (31.6%) concluded within 60 days and 204 (63.2%) within one year.
Among countries with at least 10 observations, Austria had the lowest median at 122 days, followed by Belgium at 133.5 and Poland at 187. Denmark had the highest median at 388 days, although country-level SDs were large, indicating substantial within-country variation.
| Country | Records | Median days | SD days | 90+ day delay |
|---|---|---|---|---|
| Slovenia | 1 | 27 | — | 0.0% |
| Estonia | 1 | 87 | — | 0.0% |
| Austria | 10 | 122 | 206.2 | 50.0% |
| Belgium | 18 | 133.5 | 249.1 | 50.0% |
| Poland | 10 | 187 | 235.2 | 60.0% |
| Portugal | 2 | 191 | 19.8 | 100.0% |
| Italy | 45 | 204 | 236.4 | 60.0% |
| Bulgaria | 1 | 204 | — | 100.0% |
| Luxembourg | 1 | 231 | — | 100.0% |
| France | 51 | 247 | 234.1 | 68.6% |
| Spain | 58 | 247.5 | 220.6 | 69.0% |
| Germany | 51 | 252 | 225.4 | 70.6% |
| Netherlands | 29 | 275 | 252.6 | 62.1% |
| Sweden | 12 | 317.5 | 236.8 | 66.7% |
| Lithuania | 1 | 343 | — | 100.0% |
| Greece | 3 | 358 | 177.8 | 100.0% |
| Croatia | 3 | 358 | 332.0 | 66.7% |
| Romania | 2 | 359 | 142.8 | 100.0% |
| Norway | 5 | 369 | 266.4 | 80.0% |
| Czechia | 3 | 377 | 228.0 | 66.7% |
| Hungary | 4 | 379 | 275.1 | 75.0% |
| Denmark | 12 | 388 | 234.6 | 66.7% |
Country ranking alone is insufficient for forecasting. Even the more frequently represented countries showed SDs above 200 days, so portfolio mix, site footprint and submission month should accompany country benchmarks.
A review shorter than the overall 55.5-day median was most common in August–October submissions, paediatric trials and solid-tumour cohorts. Multicountry scale, large site networks, open-label designs and autoimmune or inflammatory indications were associated with longer medians and more 90-day delays.
The strongest practical signal was submission timing: 46 of 62 August–October submissions (74.2%) finished below the median, versus 21 of 62 November–March submissions (33.9%). These are observational associations and should guide risk-adjusted planning rather than causal assumptions.
Without using year as an analytical variable, month-level patterns were pronounced. September and October had the shortest end-to-end medians at 24.5 and 31 days, while March and December reached 117 and 112 days. For Part II, April had a 40-day median, compared with 443 days in June.
August–October was the most favorable end-to-end window at 29 days, compared with 100.5 days for November–March. At Part II level, February or June submissions had a 404-day median and 43 of 47 records (91.5%) reached 90 days or longer.
Part II delay rose with operational complexity. Trials in four or more countries had a 354-day median and 53 of 67 records (79.1%) at 90 days or longer. Trials with 10 or more total sites had a 322-day median and 98 of 125 records (78.4%) at 90 days or longer.
| Factor | Lower-complexity profile | Higher-complexity profile |
|---|---|---|
| Trial countries | 1–3 countries 231.5 d median · 62.5% at 90+ d |
4+ countries 354 d median · 79.1% at 90+ d |
| Total trial sites | <10 sites 203 d median · 58.1% at 90+ d |
10+ sites 322 d median · 78.4% at 90+ d |
| Sites in the country | 1–3 sites 204 d median · 61.1% at 90+ d |
4+ sites 320 d median · 77.7% at 90+ d |
| Modality mix | Cell therapy only 191 d median · 57.1% at 90+ d |
Cell therapy plus another modality 270 d median · 72.1% at 90+ d |
| Masking | Blinded or not open label 177.5 d median · 55.8% at 90+ d |
Open label 260 d median · 71.9% at 90+ d |
Scale effects were consistent across three measures: number of countries, total sites and sites within the country. Country activation plans should therefore add contingency for both central multicountry coordination and local site-document volume.
Not every design feature separated timelines. Randomized and nonrandomized trials had nearly identical end-to-end medians of 56 and 55 days. Adaptive and nonadaptive trials had medians of 56 and 53 days, while target sample size showed virtually no continuous end-to-end correlation.
Operational configuration and submission timing were more informative than randomization, adaptive design or enrollment target. Review-risk models should prioritize country and site footprint before protocol labels alone.
Calendar days from the initial CTIS submission date to the first CTIS authorization date for the trial. This is a trial-level EU submission metric.
Calendar days from the earliest Part II submission in a country to the latest decision or authorization recorded for that country. This is the only country-specific timeline in the report.
End-to-end review below 55.5 days or Part II timing below 238 days, depending on the analysis.
At least 60 days for the two-month threshold and at least 90 days for the three-month threshold.