LOCF

Missing data were replaced using the last observation carried forward (LOCF) method.

Over the same time, the ejection fraction increased by 11% (PP) and 8% (LOCF) (see Webpage: Echocardiographic Changes).

Because in the Kava group 5 drop-outs occurred whereas in the Opipramol group not one patient withdrew, the main analysis was performed with the ITT population applying the LOCF procedure to ensure a more conservative approach avoiding any bias in favour of Kava.

On day 7 (LOCF), BSS decreased by 5.9 [+ or -] 2.9 points under EPs 7630 and by 3.2 [+ or -] 4.1 points under placebo (p <0.0001).

Mean TSQM values by domain for the ITT LOCF population all patients Cohort n Domain Effectiveness Convenience D0 D30 D60 D90 EP D0 TThE bid 52 44.9 51.6 (*) 52.9 (*) 52.8 (*) NA 56.7 TThE tid 17 37.3 53.1 (*) 52.6 (*) 50.0 (*) 59.2 (*) 56.9 TThE all 69 43.0 52.0 (*) 52.8 (*) 52.1 (*) 54.3 56.8 TThN bid.

Variables N = 41 Time on follow-up (months), mean [+ or -] DP 108.2 [+ or -] 52.8 Partial remission, n(%) 20 (48.78) Complete remission, n(%) 11 (26.8) Spontaneous remission, n(%) 15 (36.6) Time to remission since diagnosis 358 [+ or -] 180 (days), mean [+ or -] DP Proteinuria (g/g or g/24h) (1), 2.6 [+ or -] 3 mean [+ or -] DP (median = 2) Serum creatinine (mg/dL) (1), 2.2 [+ or -] 1.1 mean [+ or -] DP eGFR (mL/min/1.73[m.sup.2]) (1), 38.2 [+ or -] 19.5 mean [+ or -] DP (1) eGFR--LOCF (mL/min/1.73[m.sup.2]) (1), 34.2 [+ or -] 18.7 mean [+ or -] DP eGFR: estimated glomerular filtration rate; LOCF: last observation carried forward.

All participants enrolled into the study were included in the analyses with missing data handled by using the Last Observation Carried Forward (LOCF).

Analyses pertaining the cognitive evaluation were applied on (1) observed data (no imputation) and (2) last observation carried forward (LOCF) datasets.

The controversial problem during data extraction process was that one study (Keefe, 2015) used LOCF [19] (Last observation carried forward) analysis to achieve ITT( lntention-to Treat) [20] analysis.

[15] used the last observation carried forward (LOCF) technique and Sacks et al.

The last-observation-carried- forward (LOCF) method was used for imputation of missing data, and the p value was determined based upon a 2-sample t-test.

Missing data were input in the last-observation-carried-forward (LOCF) manner.