Across 48 EU Phase II nephrology trials, the median CTIS end-to-end timeline was 107 days (SD 39.3). Country-specific CTIS Part II took a median 114 days across 131 member-state observations (SD 205.3), with substantially greater dispersion. Smaller EU footprints shortened end-to-end review, while CRO involvement, combination treatment, larger enrolment and paediatric studies were the clearest markers of prolonged Part II.
End-to-end is a trial-level EU submission metric; it is not attributable to an individual country. Part II is the country-specific ethics and local-requirements span, so member-state comparisons use Part II only.
Initial CTIS submission to first CTIS authorisation. Median 107 days; mean 89.3; SD 39.3; observed range 7–132 days.
Earliest Part II submission in a member state to the latest recorded decision or authorisation in that state. Median 114 days; mean 194.3; SD 205.3; range 5–734 days.
The Part II distribution is markedly right-skewed: the median is 114 days, but the mean rises to 194 days because a minority of country processes extend well beyond one year. Planning should therefore use both the median and a long-delay contingency.
Only 10 of 48 trials (20.8%) reached first CTIS authorisation within 60 days, rising to 38 of 48 (79.2%) within 120 days. For Part II, 47 of 131 country observations (35.9%) closed within 60 days, while 18 of 131 (13.7%) exceeded one year.
A 90-day planning assumption captures only 35.4% of end-to-end authorisations and 45.0% of Part II country decisions. A 120-day end-to-end allowance is substantially more realistic, covering 79.2% of trials.
Among countries with at least three observations, Austria had the lowest median at 46.5 days, followed by Hungary at 64 and Germany at 83. France and Belgium had the longest medians at 201 and 225 days, respectively. High SDs show that country performance was often inconsistent rather than uniformly fast or slow.
| Country | n | Median days | SD | ≤60 days | ≥180 days |
|---|---|---|---|---|---|
| Finland | 1 | 28 | — | 100.0% | 0.0% |
| Ireland | 1 | 35 | — | 100.0% | 0.0% |
| Austria | 6 | 46.5 | 308.6 | 66.7% | 33.3% |
| Sweden | 2 | 46.5 | 48.8 | 50.0% | 0.0% |
| Hungary | 3 | 64 | 274.4 | 33.3% | 33.3% |
| Bulgaria | 2 | 65 | 75.0 | 50.0% | 0.0% |
| Germany | 15 | 83 | 189.9 | 40.0% | 40.0% |
| Czechia | 6 | 101 | 121.7 | 33.3% | 33.3% |
| Greece | 3 | 110 | 54.0 | 0.0% | 33.3% |
| Portugal | 3 | 110 | 133.2 | 0.0% | 33.3% |
| Italy | 18 | 112.5 | 222.3 | 38.9% | 38.9% |
| Spain | 20 | 114 | 208.1 | 35.0% | 35.0% |
| Denmark | 7 | 114 | 306.4 | 42.9% | 28.6% |
| Netherlands | 11 | 135 | 208.2 | 36.4% | 45.5% |
| Poland | 7 | 147 | 238.7 | 28.6% | 42.9% |
| France | 19 | 201 | 196.5 | 26.3% | 57.9% |
| Belgium | 7 | 225 | 222.7 | 28.6% | 71.4% |
Country choice alone is not sufficiently predictive: Austria combined a 46.5-day median with a 308.6-day SD, and Germany combined an 83-day median with a 189.9-day SD. Country medians should be paired with trial-complexity and submission-timing signals.
The clearest end-to-end signal was EU footprint. Single-country trials reached a 77-day median, versus 115 days for 2–3 countries and 109 days for 4+ countries. The number of countries correlated positively with elapsed time (Spearman ρ=0.31).
In an exploratory multivariable model, open-label design remained associated with approximately 69% longer end-to-end time, while paediatric status was associated with approximately 58% shorter time. The small paediatric subgroup means the latter should be treated as a cohort signal, not a causal effect.
Across country observations, 84 of 131 (64.1%) took at least 60 days and 73 of 131 (55.7%) took at least 90 days. CRO involvement, combination treatment, larger planned enrolment and paediatric studies showed the largest delay gradients.
A trial-clustered model retained two strong Part II signals after accounting for scale, sponsor type and design: CRO-present observations had about 2.84× the elapsed time, and combination-treatment observations about 2.04×. These variables likely proxy operational and dossier complexity rather than causing delay themselves.
Part II submissions made in October–December had a 52-day median and 28.3% reached ≥90 days. July–September submissions had a 199-day median and 96.3% reached ≥90 days; April–June was longest at 291.5 days. No comparable, stable seasonal pattern appeared for trial-level end-to-end approval.
Submission month is a useful planning flag for Part II, but not a causal calendar rule. The observed pattern also reflects which countries and trial types entered CTIS Part II in each month.
Small-molecule country observations had the shortest modality median at 83 days. Antibody and RNA/gene programmes had medians of 210 and 225 days. Transplant/rejection and inherited/rare nephropathy observations were shortest by disease cluster, while polycystic kidney disease was longest.
Modality and disease are useful complexity markers, but their effects overlap with paediatric status, sponsor model, CRO use, country mix and enrolment scale. They are best used for scenario planning rather than deterministic forecasts.
Use 107 days as the trial-level end-to-end median and 114 days as the country-specific Part II median; do not add them mechanically because they measure overlapping CTIS processes.
Part II exceeded 180 days in 53 of 131 observations (40.5%). Build this contingency for CRO-heavy, combination, large or paediatric programmes.
Single-country EU submissions were 32 days faster than 4+ country trials and 38 days faster than 2–3 country trials at the median.
Use country medians for base scheduling and SD for contingency. A low median without low variability is not a reliable fast-track signal.
CTIS: Clinical Trials Information System. Part II: member-state assessment of ethics and local requirements. SD: standard deviation. “Faster than median” means below 107 days for end-to-end and below 114 days for Part II. Factor findings are observed associations across the full cohort and are not causal estimates.