Supplementary webappendix
This webappendix formed part of the original submission and has been peer reviewed.
We post it as supplied by the authors.
Supplement to: Greving JP, Wermer MJH, Brown RD Jr, et al. Development of thePHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled
analysis of six prospective cohort studies. Lancet Neurol 2013; published online Nov 27.
http://dx.doi.org/10.1016/S1474-4422(13)70263-1.

Appendix
The absolute 5-year risk of aneurysm rupture (%) was calculated as 1 - S(t5)exp(ß), where ß = A - B

and the baseline survival for 5 years [S(t5)] is 0.97754.
The beta coefficients from our final Cox regression model are used to calculate a linear function (A).
The latter is corrected for the averages of the patients’ risk factors (B), and the subsequent result [ß] isexponentiated and used to calculate a 5-year probability of aneurysm rupture after insertion into asurvival function.
A = 0.362 (if age 70+) + 0.302 (if hypertension present) + 0.368 (if history SAH present) + 0.822 (ifsize 7-10 mm) + 1.705 (if size 10-20 mm) + 3.046 (if size ≥ 20 mm) + 0.530 (if ACA location) - 0.617 (ifICA location) + 0.698 (if posterior communicating artery or posterior location) + 1.017 (if Japanese) +1.348 (if Finnish).
B = 1.601
As an example how to use this formula: consider a 55-year-old American man, no hypertension, noprevious SAH, with one medium-sized (8 mm) posterior circulation aneurysm. In this instance, A = 0(for age 55) + 0 (for hypertension not present) + 0 (for history SAH not present) + 0.822 (for size 8.0) +0.698 (for posterior location) + 0 (for American) = 1.520
ß = 1.520 – 1.601 = -0.081
exp (ß) = 0.922
1 - S(t5)

0.922

0.922

= 1 – 0.97754= 1 – 0.979 = 0.021 = 2.1%

He will have a 2% chance of rupture over 5 years.

Webtable 1 – Search strings

Pubmed search string#1:"intracranial aneurysm"[Title/Abstract] OR "intracranial saccular aneurysm"[Title/Abstract] OR"cerebral aneurysm"[Title/Abstract] OR "intracranial aneurysms"[Title/Abstract] OR "intracranialsaccular aneurysms"[Title/Abstract] OR "cerebral aneurysms"[Title/Abstract]#2:"risk of rupture"[Title/Abstract] OR "aneurysm rupture"[Title/Abstract] OR "risk factors"[Title/Abstract]
OR "rupture"[Title/Abstract] OR "unruptured"[Title/Abstract] OR "subarachnoid
hemorrhage"[Title/Abstract]#3:"follow-up"[Title/Abstract] OR "follow up"[Title/Abstract] OR "natural history"[Title/Abstract] OR "naturalcourse"[Title/Abstract]#1 AND #2 AND #3

Embase search string#1:‘intracranial aneurysm’:ti:ab OR ‘intracranial saccular aneurysm’:ti:ab OR ‘cerebral aneurysm’:ti:ab OR‘intracranial aneurysms’:ti:ab OR ‘intracranial saccular aneurysms’:ti:ab OR ‘cerebral aneurysms’:ti:ab#2:‘risk of rupture’:ti:ab OR ‘aneurysm rupture’:ti:ab OR ‘risk factors’:ti:ab OR ‘rupture’:ti:ab OR‘unruptured’:ti:ab OR ‘subarachnoid hemorrhage’:ti:ab – 339.423#3:'follow-up':ti:ab OR 'follow up':ti:ab OR 'natural history':ti:ab OR 'natural course':ti:ab - 688.714#1 AND #2 AND #3

Webtable 2 - Baseline characteristics of all separate cohorts
ISUIAn%1691

Juvelan%
142

SUAVe*n%374

Ishibashin%419

Wermern%
93UCASn%
5720

Patient characteristics
Women

1260 75%7654%

238 64%28067%

7075%

3805 67%

Age (in years; mean±SD)
< 40
40-49
50-59
60-69
70+

55.2 13.1
210 12%387 23%413 24%422 25%259 15%

41.8
5852
30
2010.1
41%
37%
21%
1%
0%

62.5 10.5
9 2%
30 8%
108 29%138 37%89 24%

59.8
2349
1231398511.45%
12%
29%
33%
20%

50.5
1328
33
19
010.5
14%
30%
35%
20%
0%

62.5 10.3
119 2%
463 8%
1552 27%2009 35%
1577 28%Hypertension

731 44%5136%

163 44%-4652%

2480 43%

Ever smoking

1294 77%8569%

75 41%-8092%

960 17%

Prior SAH

615 36%13192%

36 10%

143%

7783%

187

Number of aneurysms
SingleMultiple

1218 72%473 28%

109
3377%
23%

313 84%61 16%

298
12171%
29%

69
2474%
26%

4927 86%
793 14%

Aneurysm characteristics
Total of unruptured aneurysms atbaseline2362181

442529Size of aneurysms(in mm; mean±SD)< 5.0
5.0-6.9
7.0-9.9
10.0-19.9>= 20.0

6.4 5.7
1217 52%439 19%279 12%314 13%103 4%

4.7
112
42
1773

3.3 0.9
424 96%
18 4%

4.5
392
83
24
228

3.4
62%
23%
9%
4%
2%

125
3.5
74%
16%
5%
4%
2%

2.9
116
93%

6697
1.0
93%
7%

5.7 3.6
3132 47%
1854 28%1016 15%611 9%
84 1%

Aneurysm location
Anterior cerebral arteries andbranches
Internal carotid arteryposterior communicating artery
other ICAMiddle cerebral artery
Posterior circulation

242 10%1222 52%
341 14%881 37%644 27%254 11%

1579
82
58%
44%

45%
3%

75 17%
172 39%157 36%
38 9%

107
216
92
124
141
6520%
41%
17%
23%
27%
12%

16
39
20
1953
1713%
31%
16%
15%
42%
14%

1381 21%2282 34%
1037 15%1245 19%2425 36%609 9%

Ruptured aneurysms
5934
7191111
Person-years of follow-up
14005
3064
1336
1050
316
9596
* 193 patients in the SUAVe study12 had missing smoking status. This variable was introduced one year after the start of the cohort study. SAH, subarachnoid
haemorrhage.

Webfigure 1 – Kaplan-Meier estimation of aneurysm rupture.

Webfigure 2 – Calibration plot for 5-year risk of aneurysm rupture. Values depict observed and predicted
event-free survival with 95% confidence intervals. The dotted 45° line denotes ideal agreement between
predicted and observed
risk.