Clinical Trial Intelligence

How Long Do CTIS Reviews Take, and What Factors Drive Delays, in European Phase III Oncology Trials?

19 July 2026

Across 890 European Phase III oncology CTIS/EU submissions, median end-to-end approval time was 64.5 days (SD 42.4). Only 430/890 trials (48.3%) were authorised within 60 days, while 396/890 (44.5%) required at least 90 days. The strongest delay signals were late-year submission, larger country and site footprints, ADC or bispecific-containing protocols, and high planned recruitment intensity; CRO involvement did not independently shorten timelines.

End-to-end median
64.5 days
SD 42.4 days
Country Part II median
102 days
SD 263.8 days
Within 60 days
48.3%
430 of 890 trials
At least 90 days
44.5%
396 of 890 trials

How quickly are Phase III oncology CTIS submissions approved?

The approval curve is split around the 60-day mark: 177/890 trials (19.9%) were authorised within 30 days and 430/890 (48.3%) within 60 days. By 120 days, 752/890 (84.5%) had received a first CTIS authorisation.

Cumulative end-to-end authorisation rate
≤ 30 days 177/890 · 19.9%
≤ 60 days 430/890 · 48.3%
≤ 90 days 495/890 · 55.6%
≤ 120 days 752/890 · 84.5%
≤ 180 days 887/890 · 99.7%
Initial CTIS/EU submission to first recorded CTIS authorisation; n=890 trials.
Interpretation

A 60-day planning assumption covered fewer than half of Phase III oncology CTIS submissions. A 120-day operational buffer covered 84.5%, while a 90-day target still left 44.5% of trials beyond target.

How long does the country-specific CTIS Part II cycle take?

Across 4,289 country-level Part II review cycles, the median was 102 days. Only 1,885/4,289 (43.9%) concluded within 60 days and 2,079/4,289 (48.5%) within 90 days, demonstrating a long right tail in national Part II decisions.

Cumulative country Part II decision rate
≤ 30 days 1282/4289 · 29.9%
≤ 60 days 1885/4289 · 43.9%
≤ 90 days 2079/4289 · 48.5%
≤ 120 days 2219/4289 · 51.7%
≤ 180 days 2384/4289 · 55.6%
Earliest recorded country Part II submission to latest recorded country decision/authorisation; 4,289 country-level cycles.
Interpretation

Country Part II timing was less predictable than the first EU authorisation. The large SD reflects a mixture of rapid national reviews and very delayed country decisions, so median and threshold probabilities are more decision-useful than the mean.

How do country-specific CTIS Part II timelines differ?

Country comparisons are reported only for the national CTIS Part II cycle, because end-to-end timing is a trial-level EU submission outcome rather than a country-attributable measure. Among countries with at least 100 recorded Part II cycles, Denmark had the shortest median at 29 days, followed by Sweden at 37 days and Czechia at 56 days. Romania (176 days), France (166), Germany (161), Poland (157), and Portugal (151.5) had the longest medians.

Country-specific CTIS Part II breakdown — days
Country Part II n Part II median Part II SD
Spain 488 122.5 268.5
France 488 166.0 269.4
Italy 424 142.0 268.2
Germany 405 161.0 269.3
Poland 347 157.0 254.5
Belgium 310 73.0 268.9
Netherlands 264 80.5 259.0
Czechia 191 56.0 262.3
Austria 175 125.0 273.2
Greece 164 131.5 254.9
Hungary 145 121.0 254.4
Denmark 137 29.0 252.7
Sweden 135 37.0 242.7
Romania 112 176.0 257.2
Portugal 110 151.5 269.5
Norway 98 30.0 256.5
Ireland 80 53.5 245.2
Finland 67 29.0 246.7
Bulgaria 54 140.5 257.2
Slovakia 37 35.0 254.2
Lithuania 20 38.5 238.5
Croatia 13 25.0 217.2
Estonia 11 32.0 272.3
Latvia 8 8 68.0 318.0
Slovenia 5 5 98.0 309.0
Cyprus 1 1 17.0
Part II values are country-specific cycles from the earliest recorded national Part II submission to the latest recorded decision or authorisation. End-to-end CTIS timing is intentionally not attributed to individual countries.
Interpretation

Country-specific Part II performance varies materially, but the very large SDs show that medians should be interpreted alongside long-tail risk. These results describe national Part II cycles; they do not isolate a country’s contribution to the coordinated Part I assessment or the overall EU submission timeline.

Which factors correlate with faster or delayed CTIS approval?

The table compares median timing, the share below the overall 64.5-day median, and the proportions delayed at least 60 or 90 days. Smaller operational footprints and April–October submissions were associated with faster authorisation; late-year timing, 61+ sites, 11+ countries, ADCs, bispecifics, high planned recruitment intensity, and lung/head-and-neck protocols were associated with substantial delay.

Factor n Median days <64.5 days ≥60 days ≥90 days Signal
Apr–Oct submission 568 48.0 56.5% 46.0% 38.6% Faster
2–5 countries 227 49.0 56.8% 46.3% 41.0% Faster
11–30 sites 218 47.5 56.4% 45.0% 39.0% Faster
Nov–Dec submission 141 119.0 29.8% 71.6% 65.2% Delayed
61+ sites 178 110.5 33.1% 68.0% 63.5% Delayed
11+ countries 142 109.5 37.3% 63.4% 58.5% Delayed
ADC-containing 100 110.5 33.0% 69.0% 65.0% Delayed
Bispecific-containing 65 111.0 32.3% 69.2% 64.6% Delayed
High recruitment intensity (>7.6 participants/month) 220 103.5 41.4% 61.8% 54.5% Delayed
Lung or head & neck 165 105.0 33.3% 68.5% 62.4% Delayed
Adjusted association

After adjustment for authorisation year, submission season, disease, modality, sample size, and design, November–December submission remained associated with 30.0% longer approval time (95% CI 14.9–47.2). Each doubling of site count correlated with 7.0% longer timing (95% CI 2.5–11.7), each doubling of country count with 5.3% longer timing (95% CI 0.6–10.2), ADC inclusion with 15.2% longer timing, and bispecific inclusion with 14.6% longer timing. In the expanded operational model, each doubling of planned monthly recruitment intensity correlated with 15.5% longer end-to-end timing (95% CI 6.7–25.1).

What additional operational factors affect CTIS timelines?

Extended testing covered sponsor and CRO structure, treatment combinations, authorised investigational medicinal product status, endpoint and eligibility burden, recruitment strategy, and the timing of national Part II submission. Two additional adjusted signals were operationally relevant: aggressive planned recruitment and late-year Part II submission.

Additional operational timing signals
Recruitment intensity
+15.5%
Longer end-to-end time per doubling of planned participants per recruitment month; 95% CI 6.7–25.1.
Late-year Part II
+38.2%
Longer national Part II cycle for November–December submissions after country and year adjustment; 95% CI 3.1–85.3.
Exploratory marker
113 days
Median for 115 trials using explicit digital or remote recruitment materials; 88/115 (76.5%) took at least 90 days, but the effect was concentrated in 2024.
Adjusted associations account for authorisation year and available trial, design, modality and operational characteristics. Recruitment intensity equals target sample size divided by planned recruitment-window months.
No independent shortcut or delay after adjustment
CRO involvement: +3.9% (95% CI −6.9 to 15.9)
EU/EEA sponsor: −2.3% (95% CI −11.1 to 7.5)
Eligibility burden: +2.6% per doubling (95% CI −1.4 to 6.7)
Endpoint burden: +1.6% per doubling (95% CI −2.3 to 5.6)
Interpretation

High planned recruitment intensity and November–December Part II submission are practical planning flags for longer CTIS/EU submission timelines. Digital recruitment should be treated as a marker of programme and dossier complexity rather than a proven cause. CRO involvement, sponsor location, endpoint count and eligibility-count burden did not independently shorten or delay review after adjustment.

Did CTIS approval times change by authorisation year?

Median end-to-end timing rose from 40 days for trials first authorised in 2024 to 112 days in 2025 and 125 days in 2026. The proportion taking at least 90 days increased from 25.2% in 2024 to 86.4% across the 2025–2026 cohort.

Authorised 2024
40 days
610 trials · 25.2% ≥90 days
Authorised 2025
112 days
197 trials · 84.8% ≥90 days
Authorised 2026
125 days
83 trials · 90.4% ≥90 days
Interpretation

Recent Phase III oncology CTIS/EU submissions in this dataset required substantially longer planning assumptions than 2024 submissions. This year effect remained the largest timing correlate after adjustment for protocol and operational characteristics.

Definitions

End-to-end CTIS approval: calendar days from the initial Clinical Trials Information System submission to the first recorded authorisation. This is a trial-level EU submission measure and is not attributed to each participating country.

Country-specific Part II: calendar days from the earliest recorded national Part II submission to the latest recorded country decision or authorisation.

Substantial delay: at least 60 days or at least 90 days, reported separately.

Planned recruitment intensity: target sample size divided by the planned recruitment-window months.

Digital or remote recruitment: explicit digital or remote patient-recruitment materials identified in the CTIS dossier.

Association: observed statistical correlation in the CTIS dataset; it does not establish that the factor caused the delay.