Across 109 Phase II infectious disease trials, the median CTIS EU submission timeline was 91 days end to end with an observed SD of 40.9 days. Country specific CTIS Part II review was longer and more variable at 153.5 median days with an SD of 209.6 days. Multi country submissions and larger site footprints were the clearest trial level markers of long end to end review, while country, open label design, orphan status, and scale differentiated Part II delay.
The end to end measure applies to the complete CTIS EU submission, not to individual countries. Median authorization was 91 days and SD was 40.9 days. Approvals accumulated sharply between 90 and 120 days: 54 of 109 trials (49.5%) were approved within 90 days, rising to 92 of 109 (84.4%) within 120 days.
The operational planning point is not 60 days. Half of Phase II infectious disease submissions had not received first authorization by 90 days, but the large majority cleared by 120 days.
Country results refer only to CTIS Part II. Across 242 country decisions, the pooled median was 153.5 days. Among countries with at least two observations, Norway had the shortest median at 30 days, followed by Portugal at 54.5 days and the Netherlands at 71 days. Ireland had the longest median at 519 days, followed by Greece at 413.5 days and Austria at 318 days.
| Country | n | Median | SD |
|---|---|---|---|
| Slovenia | 1 | 20 | 0.0 |
| Slovakia | 1 | 29 | 0.0 |
| Norway | 3 | 30 | 111.0 |
| Iceland | 1 | 52 | 0.0 |
| Portugal | 2 | 54.5 | 0.5 |
| Latvia | 1 | 55 | 0.0 |
| Netherlands | 11 | 71 | 171.8 |
| Spain | 38 | 102 | 221.3 |
| Poland | 13 | 105 | 270.4 |
| Denmark | 12 | 105.5 | 156.0 |
| Romania | 7 | 111 | 176.9 |
| Hungary | 7 | 117 | 205.0 |
| Germany | 22 | 127.5 | 231.0 |
| Czechia | 8 | 146.5 | 106.0 |
| Finland | 2 | 149 | 35.0 |
| Belgium | 16 | 160.5 | 184.8 |
| Italy | 25 | 169 | 196.4 |
| Bulgaria | 11 | 176 | 168.9 |
| Sweden | 11 | 188 | 277.4 |
| France | 34 | 210 | 208.6 |
| Austria | 4 | 318 | 152.0 |
| Croatia | 1 | 383 | 0.0 |
| Greece | 8 | 413.5 | 176.2 |
| Ireland | 3 | 519 | 166.2 |
Country choice creates a larger timing spread than the overall EU submission measure. The difference between the fastest and slowest multi observation country medians was 489 days.
Only 77 of 242 Part II decisions (31.8%) cleared within 60 days and 94 of 242 (38.8%) within 90 days. The pooled median was crossed between 120 and 180 days, and 56 of 242 decisions (23.1%) still required at least 365 days.
A 60 or 90 day Part II assumption would cover only a minority of country decisions. A portfolio plan needs country specific buffers rather than one EU wide Part II target.
Shorter than median means under 91 days. Single country submissions had a median of 83 days versus 104.5 days for multi country submissions. Trials with five or fewer sites had a median of 84 days versus 105 days above five sites. Country count correlated with duration at Spearman ρ=0.27, and site count at ρ=0.34.
Multi country trials had 5.6 times the odds of reaching 120 days compared with single country trials, while trials above five sites had 7.6 times the odds compared with smaller site footprints. Target sample size was not materially correlated with end to end duration, with Spearman ρ=0.03.
Month of initial CTIS EU submission showed a wide descriptive spread. Among months with at least five trials, March had the shortest median at 44.5 days and May the longest at 111 days, a difference of 66.5 days. March also placed 7 of 8 trials (87.5%) below the overall median, compared with 1 of 6 (16.7%) in May.
March was consistently favorable in this cohort, while May, June, September, and October clustered near or above the overall median. Month is best treated as a planning signal rather than a causal driver.
At disease group level, HIV trials had a median end to end time of 71 days, compared with 108 days for bacterial infections and 109 days for viral hepatitis. At modality level, mixed modality trials had a median of 69 days, small molecules and vaccines each 89 days, and peptide, protein, or enzyme trials 111 days.
| Group | n | Median | 120d plus |
|---|---|---|---|
| HIV | 25 | 71 | 16.0% |
| Other infectious disease | 15 | 79 | 6.7% |
| Fungal infections | 6 | 79.5 | 16.7% |
| COVID and coronaviruses | 12 | 81 | 0.0% |
| Other viral infections | 8 | 85.5 | 0.0% |
| CMV and transplant infections | 6 | 98 | 33.3% |
| Bacterial infections | 26 | 108 | 26.9% |
| Viral hepatitis | 11 | 109 | 27.3% |
| Modality | n | Median | 120d plus |
|---|---|---|---|
| Mixed modality | 19 | 69 | 0.0% |
| Small molecule | 57 | 89 | 15.8% |
| Vaccine | 15 | 89 | 13.3% |
| Peptide/protein/enzyme | 6 | 111 | 33.3% |
Bacterial infection and viral hepatitis programs were approximately five weeks slower at the median than HIV programs. Peptide, protein, or enzyme trials also showed the highest 120 day delay rate among modality groups with at least five trials at 33.3%.
For Part II, shorter than median means under 153.5 days. Randomised trials had a median of 111 days versus 185 days for non randomised trials. Open label trials had a median of 185.5 days versus 110 days for blinded or not open label trials. Orphan programs reached a median of 185.5 days and 15 of 18 decisions (83.3%) took at least 90 days.
Part II delay was primarily country and program specific. Open label and orphan programs showed higher 90 day delay odds, while larger target samples and more country sites shifted medians upward. These are exploratory associations and should not be interpreted as causal.
The data support three planning rules: use approximately 120 days as the high coverage end to end authorization horizon; model Part II separately by country; and treat multi country or larger site footprints as elevated risk for 120 day plus end to end review. A single 60 or 90 day assumption materially understates the observed Part II tail.
CTIS means Clinical Trials Information System. End to end is initial CTIS EU submission to first authorization and is not country specific. Part II is the country specific review component. SD is the descriptive population standard deviation of observed values. Shorter than median means under 91 days for end to end and under 153.5 days for Part II.