Across 1,427 European Phase II oncology trials, median CTIS review was 59 days end-to-end and the median country-specific Part II interval was 201 days. EU-level timing was most consistently associated with submission month and the number of countries, while country Part II timing varied primarily by country and selected complexity markers.
End-to-end review is an EU submission-level measure; Part II is a trial-country measure. Country performance is therefore reported only for Part II, not for end-to-end authorization.
Initial CTIS application submission to first EU authorization decision.
Earliest recorded country Part II submission to latest recorded country decision or authorization.
The two clocks are not additive and do not describe the same regulatory step. The much larger Part II SD indicates a pronounced long tail in country-level CTIS processing.
Half of EU-level CTIS decisions were reached within about two months: 720/1,427 (50.5%) by day 60. Country Part II accumulated more slowly, with 1,419/3,403 (41.7%) completed by day 90.
A 60-day assumption is realistic for only half of end-to-end reviews and 38.2% of Part II decisions. A 120-day E2E planning window covered 88.4% of trials, while 51.3% of Part II intervals still exceeded 180 days.
Among countries with at least 20 completed decisions, median Part II timing ranged from 50 days in Ireland to 301 days in Hungary—a 251-day spread. Denmark and the Netherlands were also comparatively fast at 54 and 62 days.
| Country | Decisions | Median days | SD days |
|---|---|---|---|
| Latvia | 2 | 25 | 8 |
| Estonia | 5 | 45 | 240 |
| Ireland | 32 | 50 | 247 |
| Croatia | 4 | 53 | 326 |
| Denmark | 130 | 54 | 263 |
| Netherlands | 252 | 62 | 237 |
| Portugal | 42 | 72 | 257 |
| Iceland | 1 | 88 | — |
| Austria | 84 | 94 | 221 |
| Sweden | 85 | 100 | 250 |
| Romania | 43 | 119 | 233 |
| Finland | 32 | 132 | 251 |
| Norway | 82 | 132 | 247 |
| Slovakia | 14 | 149 | 209 |
| Bulgaria | 15 | 164 | 232 |
| Lithuania | 8 | 170 | 154 |
| Belgium | 198 | 177 | 250 |
| Czechia | 68 | 194 | 278 |
| Italy | 517 | 195 | 253 |
| Slovenia | 2 | 212 | 262 |
| Poland | 171 | 222 | 258 |
| Spain | 571 | 239 | 267 |
| Germany | 372 | 254 | 264 |
| France | 549 | 260 | 274 |
| Greece | 80 | 296 | 280 |
| Hungary | 44 | 301 | 269 |
Country selection is a material Part II planning variable. Ireland, Denmark and the Netherlands had the lowest robust medians; Hungary, Greece, France and Germany had medians of 254–301 days.
EU-level end-to-end medians were lowest for August–October submissions at 34–44 days, versus 100–110 days in November–December. Part II followed a different pattern: September and November were fastest at 74 and 80 days, while April and May reached 321 and 332 days.
Month effects were not interchangeable between the EU-level and country-level clocks. In an adjusted sensitivity model, November and December remained 36% and 45% longer than January for E2E, while September and November Part II intervals were about 37% and 40% shorter than January.
Single-country trials had a 49-day E2E median, rising to 105 days for trials spanning seven or more countries. The number of countries correlated with E2E duration (Spearman ρ=0.27) but not with a trial’s median Part II duration (ρ=0.04).
Geographic breadth appears to burden the coordinated EU submission process rather than uniformly slowing each country’s Part II clock. Sample size and number of investigational products showed essentially no E2E correlation (ρ≈0.00 and ρ=0.02).
Descriptively, pharmaceutical sponsorship, CRO involvement, dose escalation and open-label designs clustered with longer medians. First-in-human trials had the largest E2E gap: 105 versus 56 days.
| Factor | E2E exposed | E2E comparator | Part II exposed | Part II comparator |
|---|---|---|---|---|
| Pharmaceutical sponsor
vs Non-pharmaceutical
|
96d
n=643; ≥90d 54.1%
|
45d
n=784; ≥90d 28.6%
|
258d
n=594; ≥90d 64.1%
|
146d
n=765; ≥90d 54.2%
|
| CRO present
vs No CRO recorded
|
96d
n=555; ≥90d 53.3%
|
47d
n=872; ≥90d 31.7%
|
249d
n=513; ≥90d 62.4%
|
170d
n=846; ≥90d 56.3%
|
| Dose-escalation design
vs No dose escalation
|
92d
n=449; ≥90d 51.0%
|
50d
n=976; ≥90d 35.1%
|
261d
n=424; ≥90d 60.8%
|
174d
n=933; ≥90d 57.6%
|
| Open-label design
vs Not open label
|
71d
n=800; ≥90d 44.9%
|
48d
n=600; ≥90d 34.0%
|
254d
n=756; ≥90d 62.0%
|
132d
n=577; ≥90d 53.9%
|
| Orphan-drug trial
vs Non-orphan
|
53d
n=179; ≥90d 35.2%
|
61d
n=1248; ≥90d 40.8%
|
299d
n=168; ≥90d 64.9%
|
187d
n=1191; ≥90d 57.7%
|
| First-in-human
vs Not first-in-human
|
105d
n=65; ≥90d 56.9%
|
56d
n=1362; ≥90d 39.3%
|
230d
n=59; ≥90d 55.9%
|
198d
n=1300; ≥90d 58.7%
|
ADC presence: +22%; peptide/protein/enzyme: +33%; open label: +10%. Raw sponsor and CRO gaps attenuated to about +12% and +11%.
Pharmaceutical sponsor: +66%; dose escalation: +45%; orphan status: +43%. CRO presence itself was approximately 0% after adjustment.
The raw CRO and sponsor differences partly reflect the more complex trials they manage. Country-adjusted Part II results retained stronger associations for pharmaceutical sponsorship, dose escalation and orphan trials. These are directional associations, not causal effects.
Disease medians differed across both clocks. Sarcoma and rare solid-tumour trials were shortest in both analyses, while lung, melanoma and gynaecologic cohorts were slower on at least one clock. For E2E, ADC and peptide/protein/enzyme trials each had 102-day medians.
Disease and modality rankings are useful for benchmarking, but they overlap with sponsor, design and country mix. The adjusted analysis supported an E2E delay signal for ADC and peptide/protein/enzyme trials rather than a universal biologic-versus-small-molecule effect.
CTIS = Clinical Trials Information System. E2E = initial CTIS submission to first authorization, analyzed once per trial. Part II = earliest recorded country Part II submission to latest country decision/authorization, analyzed per trial-country interval.
All available Phase II-containing oncology cohorts were pooled and deduplicated by CTIS trial code. Submission year was not used as an analytical variable. Medians describe central timing; SD is sample standard deviation. Factor findings are exploratory associations based on descriptive comparisons and log-duration sensitivity models with month, disease, design, operational and sponsor covariates; Part II models also adjusted for country.