Across 96 Phase I–containing haematology trials, the median CTIS/EU end-to-end decision time was 73 days, while the observed country-specific CTIS Part II interval was substantially longer at 270.5 days. Only 55.2% of end-to-end decisions and 27.3% of Part II country decisions were completed within 90 days. First-in-human status, a four-or-more-country footprint, disease mix and submission month marked the clearest end-to-end differences; country, sponsor profile and CRO use were the clearest Part II separators.
The trial-level interval from initial CTIS submission to first authorization had a median of 73 days and a sample standard deviation (SD) of 49.1 days. The middle 50% of trials fell between 22.8 and 111.3 days; the observed range was 6–204 days.
A 90-day planning assumption covered only 55.2% of Phase I haematology CTIS submissions. A 120-day allowance covered 85.4%, while 180 days covered 96.9%.
Across 220 country decisions, the observed interval from the earliest Part II submission in that country to the latest recorded decision or authorization had a median of 270.5 days and SD of 233.1 days. Country medians ranged from 121.5 days in Austria to 499.0 days in Hungary among countries with at least four decisions.
Among higher-volume countries (n≥10), Belgium had the shortest median Part II interval at 201.0 days, followed by France at 237.5 days. Germany had the longest at 401.5 days, followed by Poland at 380.0 days and Italy at 325.0 days.
End-to-end CTIS/EU authorization accumulated much faster than country-specific Part II. By 90 days, 53 of 96 trials (55.2%) had an initial authorization, compared with 60 of 220 country Part II decisions (27.3%).
Two-month-or-longer delay occurred in 53 of 96 end-to-end reviews (55.2%) and 167 of 220 Part II decisions (75.9%). Three-month-or-longer delay occurred in 43 of 96 end-to-end reviews (44.8%) and 160 of 220 Part II decisions (72.7%).
The strongest descriptive differences were associated with first-in-human status, number of participating countries, disease group, modality mix and month of initial EU submission. These are cohort associations, not causal effects.
First-in-human trials had nearly twice the ≥90-day delay rate of non-first-in-human trials (69.2% vs 37.5%). Multicountry complexity also moved in the expected direction: the median increased from 60 days for one-country submissions to 103 days for four or more countries.
To avoid overweighting multicountry trials, non-country factor comparisons used one median Part II value per trial. Sponsor profile and CRO involvement showed the clearest group separation; country and Part II submission month remained major operational separators at the decision level.
The Part II signal was dominated by country and timing of the country submission. Sponsor and CRO differences persisted descriptively, but both are likely proxies for program scale, multinational complexity and vendor intensity.
Several plausible complexity measures had weak or non-monotonic relationships with review time. Their correlations were too small or inconsistent to treat as reliable planning levers in this cohort.
| Factor | End-to-end ρ | Trial-level Part II ρ | Reading |
|---|---|---|---|
| Number of countries | +0.21 | +0.16 | Longer |
| Total sites | −0.01 | +0.17 | Weak |
| Planned sample size | −0.14 | +0.16 | Mixed |
| Total endpoint count | +0.04 | −0.04 | None |
| Eligibility-criteria count | +0.03 | −0.10 | None |
| Recruitment window | −0.42 | +0.09 | Non-causal pattern |
Document volume proxies—endpoint and eligibility counts—were essentially uncorrelated with timing. The more reproducible operational signal was geographic breadth rather than the raw number of sites or planned participants.
Use separate clocks: a trial-level CTIS/EU authorization clock and a country-specific Part II clock. For first-in-human or broad multicountry programs, schedule above the 73-day cohort median; for Part II, use country-specific benchmarks rather than applying the end-to-end median to individual countries.
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