Statistics.
PHTS, SD, CLOVES, bleb nevus syndrome, venous malformation, BRBN
PTEN HAMARTOMA TUMOR SYNDROME, KAPOSIFORM HEMANGIOENDOTHELIOMA, TUFTED ANGIOMA, RARE DISEASES
In this interim analysis, we report descriptive statistics. Continuous variables are reported as mean and standard deviation (SD) or as median and interquartile range (IQR), as appropriate. Binary and categorical variables are reported as frequency and relative frequency (%). This interim analysis focused on efficacy and safety. All data were collected and managed using REDCap electronic data capture tools and analyzed using R software (In the complete VASE study, which focuses on rare diseases, all patients will be treated with the experimental treatment and the main interest is on the difference in the results measured before and after treatment. Each patient will therefore be his/her own control and comparison will be made according to paired tests (The objective is also to analyze the results according to 6 diagnostic groups: (a) venous malformation, unifocal + multifocal + blue rubber bleb nevus syndrome (BRBN) + capillaro-venous malformation; (b) LM + lymphatico-venous malformation (LVM); (c) CLVM + KTS + CLOVES; (d) Gorham + GLA; (e) PTEN hamartoma tumor syndrome (PHTS); and (f) kaposiform hemangioendothelioma (KHE) + tufted angioma. Therefore, a total of 250 patients will be enrolled in the study, providing therefore a 95% power (or more) in the 3 largest groups to detect a difference of the magnitude of the one identified in the pilot study (with no adjustment per group) if the SD is the same, or even (slightly) larger (no multiplicity adjustment for the number of groups). In the smallest of these groups; the power will be of 95% to detect a difference of 2.3 (SD 2.5), 3728 (SD 4000), 75 (SD 80) for VAS, D-dimer, and MRI score, respectively, with Wilcoxon’s signed-rank test and with a type I error of 1.25%. The power will obviously be larger in the larger groups. For QoL, however, only the largest group (a) achieves a power of 95% to detect a 10% difference in QoL score between 3 months and 12 months, assuming an SD of differences of 30. The 3 smaller groups (d, e, and f) have to be grouped with other groups, or together, to achieve a reasonable power. All statistical hypothesis tests are 2-tailed unless specific otherwise. See the detailed statistical plan in supplemental material.