Across 488 Phase III paediatric trials submitted through the EU Clinical Trials Information System (CTIS), the median end to end review was 85 days with a 44 day standard deviation. Country specific CTIS Part II review was slower and much more variable at a 120 day median and 248 day standard deviation. Initial EU submissions in May, August and February were fastest end to end, while national Part II submissions in May, July and December were associated with the longest delays.
The trial level end to end interval from initial EU CTIS submission to first authorization had a median of 85 days and SD of 44 days. The country specific Part II interval had a median of 120 days and SD of 248 days, showing a substantially longer right tail.
The national Part II component was the more variable operational risk. Its standard deviation was 5.6 times the end to end SD, despite a median only 35 days longer.
By 90 days, 247 of 487 end to end intervals had completed, equal to 50.7%. For Part II, 1,049 of 2,251 country decisions had completed by 90 days, equal to 46.6%; only 54.3% had completed by 180 days.
End to end authorizations clustered around the 85 day median and reached 83.8% by 120 days. Part II decisions remained dispersed: 45.7% still lasted 180 days or longer.
Median country specific Part II review ranged from 25 days in Croatia and 27 days in Latvia to 194 days in Spain and 214 days in Portugal. Among the largest national samples, the Netherlands recorded 118 days, Poland 120 days, France 155 days, and Germany and Italy 172.5 days.
| Country | n | Median | SD |
|---|---|---|---|
| Croatia | 13 | 25 | 123.6 |
| Latvia | 9 | 27 | 151.8 |
| Denmark | 69 | 32 | 241.8 |
| Lithuania | 21 | 35 | 278.0 |
| Norway | 40 | 37.5 | 239.5 |
| Sweden | 54 | 38 | 255.3 |
| Slovakia | 35 | 41 | 218.1 |
| Finland | 33 | 45 | 246.2 |
| Slovenia | 4 | 59.5 | 257.2 |
| Czechia | 79 | 61 | 218.9 |
| Austria | 68 | 64.5 | 237.5 |
| Hungary | 75 | 83 | 246.1 |
| Estonia | 11 | 112 | 169.0 |
| Netherlands | 133 | 118 | 253.6 |
| Romania | 52 | 120 | 239.1 |
| Poland | 203 | 120 | 242.5 |
| France | 236 | 155 | 251.1 |
| Ireland | 33 | 168 | 226.1 |
| Belgium | 148 | 171 | 247.2 |
| Bulgaria | 55 | 172 | 243.9 |
| Greece | 56 | 172.5 | 252.5 |
| Germany | 236 | 172.5 | 259.9 |
| Italy | 244 | 172.5 | 256.5 |
| Spain | 275 | 194 | 247.9 |
| Portugal | 69 | 214 | 245.2 |
Country selection materially changes the Part II risk profile. The median gap between Croatia and Portugal was 189 days, while large SDs show that even faster median countries could produce long outliers.
Faster than median means below 85 days. Initial CTIS submissions in May, August and February had medians of 47, 43 and 50.5 days, with 63.3% to 66.0% finishing below the cohort median. November submissions had a 122 day median and 83.3% lasted at least 90 days.
The clearest end to end correlates were submission timing, multinational scale, randomisation and therapeutic context. These are descriptive associations, but the 47 day May median versus 122 days in November and the 61 day single country median versus 108 days for 8+ countries are operationally meaningful differences.
Country Part II submission month showed the largest timing spread. June and October submissions had medians of 44 and 47.5 days, while May, July and December reached 360, 260 and 300.5 days. At least 90 day review occurred in 77.6% of May submissions and 71.4% of July submissions.
Part II delay was associated more strongly with country, submission month and therapeutic context than with the number of sites inside a country. Vaccine programs had a 252.5 day median and 79.6% lasted at least 90 days, compared with 66 days and 47.6% for monoclonal antibodies.
Phase III paediatric EU submissions should be planned as two distinct timing problems: the overall CTIS route and the national Part II route. The same multinational footprint that correlated with a longer 108 day end to end median for 8+ country trials correlated with a shorter 63 day Part II median, suggesting that parallel execution and country selection can offset local review risk.
Initial CTIS submission in May, August or February; single country or ≤5 site scope; nonrandomised or biomarker stratified design; oncology, cell therapy or monoclonal antibody context; Part II submission in June or October.
Initial CTIS submission in November or January; 8+ country or 41+ site scope; randomised design; dermatology, cardiology, vaccines or oligonucleotides; Part II submission in May, July or December and slower national markets.
End to end is the interval from initial EU CTIS submission to first authorization for the trial. Part II is the country specific interval from the earliest recorded Part II submission to the latest decision or authorization. Shorter than median means below 85 days end to end or below 120 days for Part II. SD is sample standard deviation. Associations are descriptive and do not establish causality.