EU Phase II Neurology CTIS Timelines and Contributing Factors
Across 247 Phase II neurology trials, the median end-to-end interval from initial Clinical Trials Information System (CTIS) submission to first EU authorization was 100 days (SD 43.8). Across 677 country-level CTIS Part II decisions, the median was 137 days (SD 252.7), and 370/677 (54.7%) reached 90 days or longer. Member state, submission month, site burden, third-party complexity, CRO involvement, adaptive design and orphan status showed the largest descriptive associations with timing.
How quickly are Phase II neurology trials authorized through EU CTIS?
Only 42/247 trials (17.0%) reached first authorization within 30 days of initial CTIS submission. The cumulative share rose to 84/247 (34.0%) by 60 days, 107/247 (43.3%) by 90 days and 197/247 (79.8%) by 120 days.
The 100-day median means a 90-day end-to-end planning assumption would cover fewer than half of Phase II neurology submissions: 107/247 (43.3%) were authorized by that point.
How long does country-specific CTIS Part II take?
Across 677 member-state decisions, 170 (25.1%) completed within 30 days, 285 (42.1%) within 60 days and 308 (45.5%) within 90 days. The 137-day median and 252.7-day SD show a long right tail rather than a tightly clustered process.
CTIS Part II is the country-specific component. A 60-day assumption covered 285/677 decisions (42.1%); 397/677 (58.6%) took at least 60 days and 370/677 (54.7%) took at least 90 days.
Which countries show the shortest and longest CTIS Part II timelines?
Among countries with at least five observations, Denmark had the shortest median at 27 days (n=17), followed by Sweden at 32.5 days (n=16) and Finland at 35.5 days (n=8). Norway had the longest median at 282 days (n=10), followed by Austria at 276 days (n=15) and Germany at 254 days (n=71).
| Country | n | Median days | SD | ≤60 days | ≥90 days |
|---|---|---|---|---|---|
| Cyprus | 1 | 2.0 | — | 100.0% | 0.0% |
| Latvia | 2 | 25.5 | 9.2 | 100.0% | 0.0% |
| Denmark | 17 | 27.0 | 189.8 | 64.7% | 35.3% |
| Lithuania | 2 | 27.0 | 7.1 | 100.0% | 0.0% |
| Sweden | 16 | 32.5 | 252.0 | 56.2% | 37.5% |
| Finland | 8 | 35.5 | 282.4 | 75.0% | 25.0% |
| Slovakia | 7 | 37.0 | 215.8 | 57.1% | 42.9% |
| Belgium | 34 | 43.0 | 266.4 | 55.9% | 41.2% |
| Hungary | 15 | 54.0 | 208.2 | 53.3% | 40.0% |
| Ireland | 5 | 60.0 | 298.9 | 60.0% | 40.0% |
| Netherlands | 55 | 68.0 | 284.2 | 47.3% | 49.1% |
| Czechia | 36 | 86.5 | 206.4 | 44.4% | 47.2% |
| Bulgaria | 12 | 94.0 | 236.3 | 41.7% | 50.0% |
| Poland | 63 | 110.0 | 248.8 | 44.4% | 52.4% |
| Greece | 7 | 118.0 | 164.4 | 28.6% | 71.4% |
| Romania | 8 | 127.0 | 244.6 | 37.5% | 62.5% |
| Iceland | 1 | 143.0 | — | 0.0% | 100.0% |
| Italy | 82 | 170.0 | 266.4 | 29.3% | 68.3% |
| France | 91 | 176.0 | 244.9 | 40.7% | 53.8% |
| Spain | 98 | 176.5 | 251.2 | 42.9% | 55.1% |
| Portugal | 15 | 181.0 | 243.0 | 26.7% | 66.7% |
| Germany | 71 | 254.0 | 266.4 | 33.8% | 64.8% |
| Austria | 15 | 276.0 | 268.3 | 40.0% | 60.0% |
| Norway | 10 | 282.0 | 287.9 | 30.0% | 70.0% |
| Slovenia | 2 | 400.5 | 348.6 | 0.0% | 100.0% |
| Croatia | 3 | 581.0 | 168.6 | 0.0% | 100.0% |
| Luxembourg | 1 | 663.0 | — | 0.0% | 100.0% |
Country selection materially changes the expected Part II path. The difference between Denmark and Norway was 255 median days among countries with at least five observations.
Does the month of CTIS submission correlate with review time?
Month showed a stronger gradient for Part II than for end-to-end review. December, January and March Part II submissions had medians of 42.0, 39.0 and 39.5 days, while April, July and August had medians of 368.0, 273.0 and 296.0 days. For end-to-end review, September was shortest at 45 days and November longest at 116 days.
| Month | End-to-end | Part II | ||||
|---|---|---|---|---|---|---|
| n | Median | ≥90d | n | Median | ≥90d | |
| January | 19 | 94.0 | 57.9% | 66 | 39.0 | 40.9% |
| February | 10 | 107.0 | 70.0% | 57 | 80.0 | 47.4% |
| March | 19 | 98.0 | 52.6% | 60 | 39.5 | 40.0% |
| April | 18 | 91.5 | 55.6% | 67 | 368.0 | 65.7% |
| May | 11 | 102.0 | 63.6% | 56 | 268.5 | 60.7% |
| June | 17 | 108.0 | 64.7% | 44 | 239.5 | 61.4% |
| July | 21 | 112.0 | 71.4% | 49 | 273.0 | 77.6% |
| August | 24 | 84.0 | 41.7% | 59 | 296.0 | 76.3% |
| September | 27 | 45.0 | 37.0% | 74 | 74.5 | 48.6% |
| October | 29 | 113.0 | 58.6% | 62 | 123.5 | 58.1% |
| November | 27 | 116.0 | 77.8% | 43 | 88.0 | 48.8% |
| December | 25 | 100.0 | 52.0% | 40 | 42.0 | 27.5% |
For CTIS Part II, April submissions were 326 median days longer than December submissions. This is a scheduling signal, not proof that the calendar month itself causes delay.
What correlates with shorter-than-median end-to-end authorization?
“Shorter” means below the 100-day trial-level median. Smaller site footprints, fewer external parties, no CRO and non-pharmaceutical sponsorship were the clearest operational signals.
Increasing from 1–3 to 26+ sites added 25 median days and reduced the share below the 100-day median from 62.1% to 29.7%. The number of sites correlated positively with end-to-end days (Spearman ρ=0.23).
What correlates with 60- and 90-day CTIS Part II delays?
For country-specific Part II, complexity markers were more pronounced. Adaptive trials, orphan programmes, CRO-supported submissions, larger trial footprints and more external parties all showed higher medians and higher ≥90-day rates.
The largest operational contrast was between trials with 1–3 total sites and 11–25 sites: median Part II differed by 219 days, while the ≥90-day rate rose from 40.4% to 65.8%.
Which neurology diseases and modalities show the greatest Part II variation?
Disease and modality were associated with different CTIS Part II profiles. Migraine/headache and neuro-oncology groups had medians of 32 and 22 days, whereas sleep disorders and epilepsy/neurodevelopmental trials reached 304 and 321 days. Protein/peptide programmes had a 37-day median versus 203 days for small molecules and 219 days for gene therapy.
| Disease group | n | Median | <137d | ≥90d |
|---|---|---|---|---|
| Neuro-oncology | 25 | 22.0 | 80.0% | 20.0% |
| Migraine / headache | 27 | 32.0 | 96.3% | 7.4% |
| Stroke / acute brain injury | 58 | 40.0 | 69.0% | 37.9% |
| Movement disorders | 54 | 63.5 | 53.7% | 48.1% |
| Neuromuscular / motor neuron | 124 | 80.0 | 56.5% | 49.2% |
| Other neurology | 108 | 126.5 | 50.9% | 53.7% |
| Dementia / cognitive disorders | 99 | 168.0 | 41.4% | 64.6% |
| Demyelinating disease | 101 | 232.0 | 42.6% | 60.4% |
| Sleep disorders | 35 | 304.0 | 5.7% | 94.3% |
| Epilepsy / neurodevelopmental | 46 | 321.0 | 21.7% | 82.6% |
| Modality | n | Median | <137d | ≥90d |
|---|---|---|---|---|
| Protein / peptide | 86 | 37.0 | 68.6% | 32.6% |
| Radiopharmaceutical combination | 35 | 39.0 | 74.3% | 34.3% |
| Multi-modality | 57 | 42.0 | 64.9% | 40.4% |
| Monoclonal antibody | 99 | 169.0 | 48.5% | 57.6% |
| Small molecule | 284 | 203.0 | 40.1% | 64.1% |
| Oligonucleotide | 42 | 208.5 | 38.1% | 61.9% |
| Gene therapy | 19 | 219.0 | 42.1% | 63.2% |
Disease and modality signals partly reflect where and how studies are submitted. They are most useful for benchmarking a like-for-like EU CTIS programme, not for claiming that a therapeutic class directly causes delay.
What should EU neurology submission teams plan for?
The pooled data support four practical planning anchors for Phase II neurology CTIS submissions.
Use the trial-level median as the central end-to-end CTIS authorization benchmark; only 43.3% completed within 90 days.
Use the country-specific median for Part II planning, then replace it with member-state medians when the country mix is known.
Observed Part II median difference between 1–3-site and 11–25-site trial footprints; build more contingency for complex networks.
≥90-day Part II rate was 27.5% for December submissions and 65.7% for April submissions; sequence readiness around month-level patterns.
Definitions
EU CTIS end-to-end: calendar days from initial CTIS submission to first trial authorization. It is a trial-level outcome and is not attributed to individual countries.
CTIS Part II: country-specific review covering local and ethical aspects; calculated from the earliest Part II submission date to the latest country decision or authorization date in the dataset.
Shorter than median: <100 days for end-to-end and <137 days for Part II. Substantial delay thresholds are ≥60 and ≥90 days.
SD: standard deviation, showing dispersion around the mean; high Part II SD reflects the observed long tail.