Across 247 Phase III neurology trials, the median end-to-end European Union Clinical Trials Information System (EU CTIS) timeline was 97 days (SD 41.6). The 1,018 country-specific Part II decisions had a similar median of 99.5 days, but a far wider SD of 243.8 days: 535 of 1,018 decisions (52.6%) concluded within 120 days, while 324 (31.8%) exceeded 365 days. Country, Part II submission month, site footprint, paediatric status, disease, modality and operational complexity showed the clearest associations with timing.
End-to-end timing runs from the initial EU CTIS submission to the first trial authorisation and is therefore a trial-level European measure, not a country metric. Part II timing runs from each country’s Part II submission to its latest country decision or authorisation and is the only timeline reported by country.
The two medians are nearly identical, but country Part II has a much heavier tail: its 75th percentile is 437.8 days versus 115.5 days for end-to-end EU CTIS authorisation.
EU CTIS end-to-end authorisation accelerates sharply between 90 and 120 days: the cumulative completion rate rises from 117 of 247 trials (47.4%) to 210 of 247 (85.0%). Country Part II decisions rise only from 491 of 1,018 (48.2%) to 535 of 1,018 (52.6%) over the same interval.
A 120-day planning assumption captures 85.0% of first EU CTIS authorisations but only 52.6% of Part II country decisions. Even a 365-day Part II assumption captures 68.2%, leaving 31.8% beyond one year.
Among countries with at least five decisions, Finland had the shortest Part II median at 24.5 days (n=12), followed by Denmark and Estonia at 27 days. Latvia had the longest median at 252 days (n=7), followed by Belgium at 226.5 and Spain at 196.5 days.
| Country | n | Median | SD |
|---|---|---|---|
| Cyprus | 1 | 14 | — |
| Finland | 12 | 24.5 | 243.2 |
| Denmark | 49 | 27 | 207.9 |
| Estonia | 6 | 27 | 228.8 |
| Norway | 16 | 31.5 | 260.8 |
| Lithuania | 7 | 33 | 264.2 |
| Ireland | 10 | 36.5 | 222.1 |
| Austria | 24 | 47.5 | 243.7 |
| Sweden | 26 | 47.5 | 252.9 |
| Czechia | 39 | 49 | 228.5 |
| Slovakia | 23 | 56 | 209.0 |
| Bulgaria | 23 | 67 | 237.4 |
| Hungary | 32 | 77.5 | 233.3 |
| Slovenia | 6 | 78.5 | 290.8 |
| Romania | 21 | 96 | 252.5 |
| Netherlands | 56 | 99.5 | 252.7 |
| Greece | 26 | 101.5 | 220.8 |
| France | 113 | 122 | 233.7 |
| Croatia | 14 | 148 | 283.2 |
| Italy | 113 | 148 | 252.2 |
| Portugal | 38 | 165.5 | 253.0 |
| Germany | 97 | 168 | 255.2 |
| Poland | 93 | 181 | 246.3 |
| Spain | 112 | 196.5 | 249.1 |
| Belgium | 54 | 226.5 | 243.6 |
| Latvia | 7 | 252 | 202.1 |
Country selection materially changes expected Part II timing. The median gap between Finland and Latvia is 227.5 days, while large SDs of 202.1–290.8 days in many countries show that the median should be paired with a long-tail contingency.
The clearest end-to-end associations were operational scale and complexity. Trials with 31+ EU sites had a median of 112 days versus 69 days for trials with ≤10 sites; digital-recruitment trials had a median of 112 versus 70 days without digital recruitment.
The strongest practical signal is scale: 43 of 61 trials with 31+ sites (70.5%) took at least 90 days, compared with 50 of 107 trials with ≤10 sites (46.7%). Complex recruitment also clustered with delay: 51 of 69 digital-recruitment trials (73.9%) and 26 of 34 advocacy-recruitment trials (76.5%) took at least 90 days.
Country Part II timing was most sensitive to submission month, participant population and local operational burden. November submissions had a median of 35 days, while December submissions had a median of 437 days; paediatric trial-country decisions had a median of 290 days versus 67 days for adult trials.
Paediatric status was the largest cross-trial operational signal: 201 of 321 paediatric Part II decisions (62.6%) took ≥90 days versus 328 of 697 adult decisions (47.1%). Local site expansion also increased the median from 77 days at ≤2 sites to 141 days at 3–5 sites.
Disease and modality patterns differed between the European first-authorisation clock and country Part II. Multiple-sclerosis/demyelinating trials had the shortest end-to-end median at 50 days, yet their country Part II median was 186 days. Epilepsy Part II was longest at 300.5 days, while stroke was 42 days.
| Group | n | Median | ≥90d |
|---|---|---|---|
| Multiple sclerosis / demyelinating | 35 | 50 | 40.0% |
| Other neurology | 62 | 64.5 | 41.9% |
| Stroke / cerebrovascular | 25 | 87 | 48.0% |
| Migraine / headache | 20 | 103.5 | 60.0% |
| Movement disorders | 16 | 104.5 | 75.0% |
| Epilepsy / seizure | 21 | 108 | 61.9% |
| Alzheimer’s / dementia | 23 | 112 | 73.9% |
| Neuromuscular / motor neuron | 28 | 113.5 | 57.1% |
| Rare / neurodevelopmental | 9 | 116 | 66.7% |
| Group | n | Median | ≥90d |
|---|---|---|---|
| Gene / cell therapy | 11 | 33 | 45.5% |
| Mixed / other | 31 | 63 | 32.3% |
| Antibody-containing | 59 | 69 | 47.5% |
| Protein / peptide | 23 | 103 | 60.9% |
| Small molecule only | 123 | 104 | 61.8% |
| Group | n | Median | ≥90d |
|---|---|---|---|
| Stroke / cerebrovascular | 71 | 42 | 33.8% |
| Movement disorders | 43 | 45 | 30.2% |
| Alzheimer’s / dementia | 90 | 46 | 37.8% |
| Neuromuscular / motor neuron | 198 | 66 | 44.4% |
| Rare / neurodevelopmental | 30 | 88.5 | 50.0% |
| Migraine / headache | 86 | 113.5 | 55.8% |
| Multiple sclerosis / demyelinating | 193 | 186 | 58.0% |
| Other neurology | 204 | 238.5 | 59.8% |
| Epilepsy / seizure | 96 | 300.5 | 71.9% |
| Group | n | Median | ≥90d |
|---|---|---|---|
| Mixed / other | 89 | 27 | 33.7% |
| Protein / peptide | 76 | 81 | 48.7% |
| Antibody-containing | 350 | 93.5 | 51.1% |
| Small molecule only | 479 | 153 | 56.4% |
| Gene / cell therapy | 24 | 201 | 54.2% |
Modality is not uniformly predictive across both clocks. Gene/cell therapy was fastest end-to-end at 33 days (n=11) but slowest in Part II at 201 days (n=24 country decisions); small-molecule trials were 104 days end-to-end and 153 days in Part II.
The overall median is a useful baseline, but country-specific Part II requires a portfolio approach because the upper tail is much longer than the end-to-end EU CTIS clock.
Use 97 days as the central EU CTIS estimate and 120 days as an 85% first-authorisation benchmark. Build country Part II plans separately, using each country median and SD, and add the largest contingency for paediatric, epilepsy, multi-site and late-year Part II submissions.
EU CTIS end-to-end: initial EU CTIS submission to first CTIS authorisation; one value per trial and not attributable to individual countries.
Country-specific Part II: earliest Part II submission in a country to its latest decision or authorisation; one value per trial-country.
SD: standard deviation, used with the median to show the spread and long tail of review times.