How Fast Are Phase I Neurology CTIS Reviews—and What Drives Delay?
Across 112 European Phase I neurology trials, median end-to-end (E2E) time from initial CTIS submission to first authorization was 81.5 days (SD 44.9); 50/112 (44.6%) were authorized within 60 days. Country-specific CTIS Part II was substantially slower and more variable across 229 country decisions: median 194 days (SD 271.4), with 72/229 (31.4%) within 60 days. Denmark had the fastest country median at 27 days, while multisite, Phase I/II+, orphan and document-heavy programs showed the clearest delay signals.
How long does a Phase I neurology CTIS review take?
E2E is a trial-level metric: initial EU CTIS submission to first authorization. It is not attributable to an individual country. Country-level analysis therefore uses only the recorded CTIS Part II interval from the earliest country-specific submission to the latest decision or authorization.
The practical planning benchmark is approximately 82 days for first CTIS authorization, but country Part II should be budgeted separately. E2E reached 120 days for 94/112 trials (83.9%), whereas only 112/229 Part II decisions (48.9%) were recorded within 180 days.
How long does country-specific CTIS Part II take?
Across 18 European countries, Part II medians ranged from 27 days in Denmark to 381.5 days in Ireland. Among countries with at least five decisions, Denmark, Belgium and Austria were fastest; France, Italy and Portugal were slowest. E2E is intentionally excluded from this country table because it is not a country-level outcome.
| Country | N | Median | SD | ≤90 d |
|---|---|---|---|---|
| Denmark | 5 | 27 | 118.5 | 60.0% |
| Belgium | 14 | 82 | 311.0 | 50.0% |
| Austria | 8 | 90.5 | 228.7 | 50.0% |
| Bulgaria | 5 | 98 | 226.1 | 40.0% |
| Sweden | 9 | 98 | 251.1 | 44.4% |
| Czechia | 4 | 122.5 | 275.7 | 50.0% |
| Poland | 18 | 143 | 279.1 | 44.4% |
| Romania | 1 | 154 | — | 0.0% |
| Slovakia | 1 | 177 | — | 0.0% |
| Hungary | 4 | 182.5 | 197.1 | 0.0% |
| Spain | 31 | 220 | 298.8 | 35.5% |
| Germany | 28 | 249 | 265.4 | 32.1% |
| Netherlands | 38 | 270.5 | 285.1 | 34.2% |
| Portugal | 6 | 332.5 | 301.4 | 16.7% |
| Italy | 24 | 337 | 304.6 | 33.3% |
| France | 29 | 338 | 239.0 | 17.2% |
| Slovenia | 2 | 357 | 287.1 | 0.0% |
| Ireland | 2 | 381.5 | 301.9 | 0.0% |
Country selection materially changes the observed Part II benchmark. Among countries with at least five decisions, the median gap between Denmark (27 days) and France (338 days) was 311 days; large within-country SDs show that country alone does not fully explain delay.
Which factors correlate with faster or delayed E2E authorization?
Faster-than-median authorization means under 81.5 days; substantial delay is shown at 90 days or longer. The strongest descriptive E2E patterns were submission season, operational footprint, phase breadth, sponsor profile and disease group.
| FACTOR | FASTER PROFILE | MEDIAN | SLOWER PROFILE | MEDIAN | ≥90 D |
|---|---|---|---|---|---|
| Submission quarter | Jan–Mar (n=26) | 50.5 | Oct–Dec (n=37) | 115.0 | 54.1% |
| Countries | Single-country (n=73) | 70.0 | Multicountry (n=39) | 103.0 | 59.0% |
| Sites | One site (n=47) | 58.0 | Multiple sites (n=65) | 99.0 | 53.8% |
| Phase breadth | Phase I only (n=60) | 63.0 | Phase I/II+ (n=52) | 100.5 | 55.8% |
| Sponsor type | Non-industry (n=31) | 55.0 | Industry (n=81) | 92.0 | 51.9% |
| Disease group | Huntington’s (n=6) | 32.0 | Neuromuscular/rare (n=21) | 115.0 | 76.2% |
The clearest E2E separation was seasonal: Oct–Dec submissions were 64.5 days slower at the median than Jan–Mar. In an exploratory adjusted model, Oct–Dec remained associated with a 1.71× longer E2E interval than Jan–Mar (95% CI 1.00–2.91). Multicountry, multisite and broader-phase programs also had 33–41-day longer raw medians, but these signals overlapped with disease and sponsor complexity.
What correlates with country Part II delay?
For country Part II, faster-than-median means under 194 days. The strongest descriptive delays appeared in broader-phase, orphan, multisite, non-European-sponsored, CRO-supported and documentation-heavy applications.
Part II was most sensitive to protocol and operational complexity. After adjusting for country, submission quarter, sponsor and other design features, Phase I/II+ programs remained associated with a 2.45× longer Part II interval than Phase I-only trials, and orphan programs with a 2.27× longer interval than non-orphan programs. The raw median penalty was 172 days for multisite programs and 226 days for programs with more endpoints.
Do disease, modality and submission month change the timeline?
Disease produced a clearer E2E signal than modality. Neuromuscular and rare neurologic trials had the slowest E2E median at 115 days, while Huntington’s disease trials had a 32-day median. Modality differences were more pronounced in Part II, but remained intertwined with orphan status, route, sites and country mix.
Month was milestone-specific rather than universally favorable: Jan–Mar was fastest for E2E, but Oct–Dec was fastest for country Part II. Modality alone was less consistent than phase breadth, orphan status, sites and document complexity; RNA/oligonucleotide and gene-therapy Part II medians were high, but these programs were also enriched for rare disease and complex multicountry execution.
Which profiles concentrate two- and three-month delays?
Overall, 62/112 trials (55.4%) took at least 60 days E2E and 54/112 (48.2%) took at least 90 days. For country Part II, 158/229 decisions (69.0%) reached at least 60 days and 152/229 (66.4%) reached at least 90 days.
The ≥60-day and ≥90-day thresholds point to the same operational pattern. For E2E, Oct–Dec, multisite and broader-phase applications concentrated delay. For Part II, orphan and Phase I/II+ decisions were most exposed: 43/49 orphan country decisions (87.8%) and 106/142 Phase I/II+ decisions (74.6%) reached at least 90 days.
What planning benchmarks emerge for EU submission strategy?
Combining the strongest descriptive factors produces materially different CTIS planning ranges. These profiles are not causal forecasts, but they show how early operational choices can shift the expected authorization window.
Jan–Mar submission + one site + Phase I only (n=8). All 8/8 were below the 81.5-day median; 7/8 (87.5%) were authorized within 60 days.
Oct–Dec submission + multisite + Phase I/II+ (n=13). Nine of 13 (69.2%) took at least 90 days; only 3/13 (23.1%) were authorized within 60 days.
One site + Phase I only (n=33 country decisions). Twenty-seven of 33 (81.8%) were below 194 days; 4/33 (12.1%) extended to at least 365 days.
Multisite + Phase I/II+ (n=129 country decisions). Only 40/129 (31.0%) were below 194 days; 68/129 (52.7%) extended to at least 365 days.
For EU submission planning, the biggest upstream levers are scope discipline and country/site sequencing. A lean Phase I-only, one-site strategy showed a 111-day Part II median versus 412 days for multisite Phase I/II+ decisions—a 301-day difference. Where scientific scope permits, separating expansion-stage complexity from the initial Phase I CTIS package may reduce timeline exposure.
Definitions and analytical basis
E2E = days from initial CTIS submission to first CTIS authorization at trial level. Part II = days from earliest country-specific Part II submission to latest recorded decision or authorization in that country. SD = sample standard deviation. “Fast” means below the relevant pooled median; 60 and 90 days represent the requested two- and three-month delay thresholds. Results pool the full Phase I neurology dataset without using calendar year as a factor.
Associations are descriptive and exploratory. They support CTIS planning and benchmarking but should not be interpreted as evidence that any single trial characteristic causes faster or slower review.