Quantification of recurrence volumes after endovascular treatment of cerebral aneurysm as surrogate endpoint for treatment stability.
BACKGROUND
New coils with unproven clinical benefit enlarge the armamentarium for endovascular aneurysm treatment continuously. Large patient numbers needed to detect benefits of such new techniques prevent timely evaluation of efficacy. We propose measuring the volume of aneurysm recurrences as surrogate endpoint for coil stability. We hypothesize that this method allows detecting effects of new materials with reduced sample sizes in comparison to conventional studies with dichotomous endpoints.


METHODS
Institutional review board approval and informed consent were obtained. Fifty-nine patients with decreasing aneurysm size and at least two available follow-up time-of-flight magnetic resonance angiographies (ToF-MRAs) were included. Newly developed software for measuring aneurysm volume differences based on ToF-MRA images was used. Based on the observed recurrence volumes and retreatment rates, the sample size for future studies comparing standard versus "new coils" were calculated.


RESULTS
Mean recurrence volume was 38.92 μl (SD110.85 μl). To show a 50% reduction of retreatment rate to control (p = 0.05; power 80%) in a regular study (dichotomous endpoint), the required sample size would be n = 356 compared with n = 78 if using the continuous surrogate endpoint "recurrence volume". When extrapolating our data to data given in the literature, sample sizes could be reduced from n = 948 to n = 74 without loss of statistical power.


CONCLUSIONS
Further studies on new materials using volumetric analysis based on ToF-MRA as surrogate endpoint could substantially decrease sample size and allow a more timely assessment of possible benefit of new materials with a fraction of the cost.
Ries
Thorsten
T
Department of Neuroradiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. ries@uke.de
Wegscheider
Karl
K
Wulff
Asmus
A
Radelfahr
Kristin
K
Säring
Dennis
D
Forkert
Nils Daniel
ND
Fiehler
Jens
J
D000328:Adult; D000368:Aged; D015415:Biomarkers; D057510:Endovascular Procedures / Q000295:instrumentation / Q000379:methods*; D023381:Endpoint Determination / Q000379:methods*; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D002532:Intracranial Aneurysm / Q000175:diagnosis* / Q000601:surgery*; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015203:Reproducibility of Results; D055502:Secondary Prevention; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D015415:Biomarkers