How Long Do Phase III Rare Disease CTIS Reviews Take and What Shapes Delay?
Clinical Trial Intelligence

How Long Do Phase III Rare Disease CTIS Reviews Take and What Shapes Delay?

20 July 2026

Across 261 Phase III rare disease trials submitted through the European Union Clinical Trials Information System (CTIS), the median end to end interval from initial CTIS submission to first authorization was 98 days, with a standard deviation (SD) of 43.2 days. Only 112 of 261 trials (42.9%) reached first authorization within 60 days, while 212 (81.2%) did so within 120 days. Country specific CTIS Part II spans were more dispersed, with a median of 159.5 days and SD of 243.9 days across 1,394 country records. Submission month, site footprint, digital recruitment, adaptive design and modality showed the clearest descriptive associations with speed or delay.

Trials analyzed
261
Phase III rare disease trials
End to end median
98 days
SD 43.2 days
Country Part II median
159.5 days
SD 243.9 days
Authorized within 60 days
42.9%
112 of 261 end to end

Two CTIS review clocks tell different operational stories

The trial level end to end CTIS clock had a 98 day median, SD 43.2 days and interquartile range of 36 to 116 days. The country specific Part II clock had a 159.5 day median, SD 243.9 days and interquartile range of 28 to 453.8 days across 1,394 country records.

Overall EU CTIS timeline summary
End to end
98 d
SD 43.2 d
IQR 36–116 d
Range 6–199 d
Country Part II
159.5 d
SD 243.9 d
IQR 28–453.8 d
Range 0–904 d
End to end is measured from initial EU CTIS submission to first authorization. Country Part II is measured from the earliest recorded Part II submission in that country to the latest recorded country decision or authorization.
Interpretation

End to end is the correct trial level EU submission metric. It is not assigned to individual countries. Country comparisons in this report therefore use CTIS Part II only.

Fewer than half of EU CTIS submissions cleared within 90 days

End to end, 45 of 261 trials (17.2%) were authorized within 30 days, 112 (42.9%) within 60 days and 126 (48.3%) within 90 days. At the substantial delay thresholds, 150 of 261 (57.5%) took at least 60 days and 135 (51.7%) took at least 90 days. The cumulative share reached 212 of 261 (81.2%) by 120 days. For country Part II, 381 of 1,394 records (27.3%) closed within 30 days, 563 (40.4%) within 60 days and 615 (44.1%) within 90 days.

Cumulative share completed by interval
End to end Country Part II
Within 30 days End to end 17.2% · Part II 27.3%
Within 60 days End to end 42.9% · Part II 40.4%
Within 90 days End to end 48.3% · Part II 44.1%
Within 120 days End to end 81.2% · Part II 47.2%
Within 180 days End to end 99.6% · Part II 51.6%
Cumulative percentages. End to end denominator: 261 trials. Country Part II denominator: 1,394 country records.
Interpretation

A 60 day planning assumption covered only 42.9% of first EU authorizations. A 120 day end to end planning window covered 81.2%, making it a materially more realistic operational base case for this cohort.

Country Part II medians ranged from 14 to 392 days

Among countries with at least 15 Part II records, Finland had the shortest median at 22 days (SD 119.7), followed by Denmark at 30.5 days (SD 206.2), Norway at 39.5 days (SD 265.4) and Sweden at 48.5 days (SD 258.1). The longest high volume medians were Spain and Belgium at 228 days, Italy at 226 days and Germany at 193.5 days.

Country specific CTIS Part II duration
Country n Median d SD d
Cyprus 3 14 186.5
Finland 15 22 119.7
Estonia 5 29 247.7
Denmark 40 30.5 206.2
Norway 24 39.5 265.4
Sweden 42 48.5 258.1
Ireland 21 57 261.9
Croatia 9 68 255.3
Portugal 42 69.5 243.1
Romania 28 69.5 165.0
Slovenia 9 91 317.5
Hungary 39 134 240.7
Greece 40 134.5 211.7
Latvia 4 140 169.1
Austria 52 149.5 229.6
Netherlands 83 153 255.5
France 163 170 254.4
Poland 115 174 234.6
Czechia 53 176 235.1
Germany 156 193.5 245.4
Bulgaria 26 216 203.3
Italy 160 226 250.9
Belgium 83 228 247.4
Spain 163 228 250.5
Slovakia 13 248 309.5
Lithuania 6 392 264.2
Sorted by median. Country values are CTIS Part II only; no country level end to end statistic is shown.
Interpretation

Country medians were operationally meaningful, but SDs were large in nearly every market. Country selection therefore changes the expected Part II midpoint, while individual trial and country sequence still drive substantial variation.

Submission month was the clearest timing signal

July EU CTIS submissions had the shortest median at 31 days, with 16 of 25 trials (64.0%) below the 98 day cohort median. February submissions had a 41 day median and May submissions 50 days. November was slowest at 121 days, followed by December at 118 days and October at 116 days; 15 of 21 November submissions (71.4%) took at least 90 days.

Median end to end duration by submission month
January n=12
103.5 d
33.3% below 98 d · 66.7% ≥90 d
February n=19
41 d
63.2% below 98 d · 36.8% ≥90 d
March n=22
106.5 d
45.5% below 98 d · 59.1% ≥90 d
April n=19
50 d
63.2% below 98 d · 42.1% ≥90 d
May n=26
50 d
65.4% below 98 d · 34.6% ≥90 d
June n=21
81 d
57.1% below 98 d · 47.6% ≥90 d
July n=25
31 d
64.0% below 98 d · 36.0% ≥90 d
August n=11
63 d
63.6% below 98 d · 36.4% ≥90 d
September n=29
99 d
44.8% below 98 d · 58.6% ≥90 d
October n=35
116 d
34.3% below 98 d · 65.7% ≥90 d
November n=21
121 d
28.6% below 98 d · 71.4% ≥90 d
December n=21
118 d
42.9% below 98 d · 57.1% ≥90 d
Months are pooled across the full cohort; year is not used as an analytical factor. Overall month differences were statistically significant by Kruskal Wallis test, p<0.001.
Interpretation

The late year cluster was materially slower: October through December medians were 116 to 121 days, compared with 31 to 50 days for February, April, May and July. Submission timing should therefore be treated as a planning variable, not only a calendar detail.

Complexity markers concentrated the 90 day delay risk

Trials using digital or remote recruitment had a 112 day median: 56 of 79 (70.9%) took at least 60 days and 53 (67.1%) took at least 90 days, versus 94 of 182 (51.6%) and 82 (45.1%) without digital recruitment. Adaptive trials had a 109 day median, with 18 of 25 (72.0%) at least 60 days and 16 (64.0%) at least 90 days. Trials with more than 32 sites had a 112 day median, with 41 of 63 (65.1%) at least 60 days and 39 (61.9%) at least 90 days, versus 76.5 days, 109 of 198 (55.1%) and 96 (48.5%) among smaller site footprints.

Median duration, below median share and delay thresholds
Digital or remote recruitment
Yes · n=79
112 d
32.9% below 98 d
70.9% ≥60 d · 67.1% ≥90 d
No · n=182
62.5 d
57.1% below 98 d
51.6% ≥60 d · 45.1% ≥90 d
Adaptive design
Yes · n=25
109 d
36.0% below 98 d
72.0% ≥60 d · 64.0% ≥90 d
No · n=234
95 d
50.9% below 98 d
56.4% ≥60 d · 50.9% ≥90 d
Randomised design
Yes · n=160
103.5 d
45.0% below 98 d
61.2% ≥60 d · 55.6% ≥90 d
No · n=100
63.5 d
57.0% below 98 d
52.0% ≥60 d · 46.0% ≥90 d
Site footprint
>32 sites · n=63
112 d
38.1% below 98 d
65.1% ≥60 d · 61.9% ≥90 d
≤32 sites · n=198
76.5 d
53.5% below 98 d
55.1% ≥60 d · 48.5% ≥90 d
Paediatric population
Yes · n=139
65 d
55.4% below 98 d
54.7% ≥60 d · 47.5% ≥90 d
No · n=122
105 d
43.4% below 98 d
60.7% ≥60 d · 56.6% ≥90 d
Associations are descriptive and based on trial level end to end CTIS duration. Below median means under 98 days; substantial delay is reported at both at least 60 days and at least 90 days. Factors were screened across geography, design, recruitment, eligibility, endpoints, sponsor and drug variables.
Interpretation

Digital recruitment, adaptive design, randomisation and a large site footprint were all associated with longer EU CTIS review times. Paediatric trials moved faster in this cohort, with a 65 day median versus 105 days for non paediatric trials.

Modality and disease showed additional separation

Cell therapy records had a 35 day median and gene therapy 41 days, compared with 106.5 days for peptide, protein or enzyme modalities. At disease level among groups with at least five trials, sickle cell disease was shortest at 42 days, while myasthenia gravis was longest at 118 days and 8 of 9 trials (88.9%) took at least 90 days.

Modality signals
Modality n Median ≥90 d
Cell therapy 17 35 29.4%
Gene therapy 17 41 35.3%
Oligonucleotide 20 57.5 45.0%
Small molecule 130 79.5 49.2%
Monoclonal antibody 60 88.5 50.0%
Peptide/protein/enzyme 56 106.5 60.7%
Disease signals, n≥5
Disease n Median ≥90 d
Sickle cell disease 5 42 40.0%
Fabry disease 6 75.5 50.0%
Phenylketonuria 5 103 60.0%
IgA nephropathy 5 108 80.0%
CIDP 5 115 80.0%
Hereditary angioedema 11 117 72.7%
Myasthenia gravis 9 118 88.9%
Modality categories may overlap when a trial includes more than one modality. Disease rows are restricted to groups with at least five trials.
Interpretation

Modality did not produce a uniform complexity penalty. In this cohort, gene and cell therapy trials were faster than protein or enzyme trials. Disease specific results were more variable and should be treated as directional where denominators were small.

What the data imply for EU CTIS planning

Base case
Use 98 days as the cohort midpoint for first EU authorization. A 120 day window covered 212 of 261 trials (81.2%).
Delay watch
November submissions, digital recruitment and more than 32 sites each carried a ≥90 day rate above 60%: 71.4%, 67.1% and 61.9%, respectively.
Definitions
CTIS: Clinical Trials Information System. End to end: initial EU CTIS submission to first authorization. Part II: country specific ethical, site and local-document review span from earliest recorded Part II submission to latest recorded country decision or authorization. SD: standard deviation. Fast: shorter than the 98 day cohort median.