Glucorticoid dose tapering in Macrophage Activation Syndrome
Thomas Weissensteiner
2025-5-06
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About myself: www.linkedin.com/in/ThomasWs-Mopfair
1. Background
1.1. Macrophage activation syndrome
Macrophage activation syndrome (MAS) is a severe inflammatory
condition that complicates the course of rheumatological disorders. It
affects mainly in young people. The symptoms include cytopenia, liver
dysfunction with coagulopathy, and neurological manifestations. There is
a high risk of rapid progression to multiorgan failure and death.
Treatment of MAS remains largely empirical, despite great improvements
in diagnosis and management. Current standard therapy includes high
doses of glucocorticoid (GC) but these can have severe longterm side
effects, especially in children 1. High GC doses are
generally given intravenously, and high dose pulses are the regimen of
choice where low-dose steroid therapy is inadequate 2. E.g.,
methylprednisolon doses ranged from 2 to 30mg/kg/day, including
10–30mg/kg/day, in almost 60% of studies 1. Recently,
high-dose GCs together with IL-1 and IFNγ inhibitors have shown
promising results, especially in MAS associated with systemic juvenile
idiopathic arthritis 1.
1.2. The challenge
“Wonderful Wednesdays” are a monthly webinar organised by the Visualisation Special Interest Group of Statisticians in the Pharmaceutical Industry (PSI).
The data were provided based on two pooled open-label studies in children (n=39) with a diagnosis of MAS disease currently receiving GC treatment. Enrolled subjects started a new investigational drug on day 1, and one objective of the study was to reduce (taper) the GC dose to a safe level during the 8 week interventional period.
The data include daily GC doses levels for the 56 day interventional period, and also weekly average GC doses (week 1-8).
Variable Name Variable Label
SUBJID Subject identifier for the study
ASTDY Analysis relative start day
AVAL1 Daily glucocorticoid dose (mg/kg/day)
AVISITN Analysis visit (N)
AVISIT Analysis visit
AVAL2 Weekly average glucocorticoid dose
The visualisations should address the following questions:
- How effective was the new investigational drug in reducing GC doses
over 8 weeks?
- What proportion of subjects achieved GC doses between clinically
important thresholds of 1.0, 0.5 and 0.2 mg/kg/day, and how did this
change over time?
- How much variability was there in GC doses, e.g. characterise shifts between threshold levels at the individual subject level?
A recording of the session can be found in PSI’s video-on-demand library: PSI VisSIG Wonderful Wednesday 62: Macrophage Activation Syndrom
2. R libraries and example data
## - Chunk libraries_and_data
# R version 4.3.0
# Load R libraries - #
library(dplyr) # version 1.1.4 # general grammar
library(tidyr) # version 1.3.1 # pivot_longer, pivot_wider
library(purrr) # version 1.0.2 # map, map2
library(DescTools) # version 0.99.58 # SomersDelta
library(scales) # version 1.3.0 # scale_y_continuous(label = percent)
library(ggplot2) # version 3.4.0 # generation of plots
library(patchwork) # version 1.3.0 # assembly of plots
# Get the data file
WW_GCdose <- read.csv("https://raw.githubusercontent.com/VIS-SIG/Wonderful-Wednesdays/refs/heads/master/data/2025/2025-04-09/WW_GCdose.csv")
WW_GCdose %>% {print(as_tibble(.), n = nrow(.) )}## # A tibble: 2,189 × 6
## SUBJID ASTDY AVAL1 AVISITN AVISIT AVAL2
## <int> <int> <dbl> <int> <chr> <dbl>
## 1 1 0 0.521 0 Baseline 0.521
## 2 1 1 0.521 1 Week 1 (study day 1 to 7) 0.938
## 3 1 2 0.521 1 Week 1 (study day 1 to 7) 0.938
## 4 1 3 0.521 1 Week 1 (study day 1 to 7) 0.938
## 5 1 4 1.25 1 Week 1 (study day 1 to 7) 0.938
## 6 1 5 1.25 1 Week 1 (study day 1 to 7) 0.938
## 7 1 6 1.25 1 Week 1 (study day 1 to 7) 0.938
## 8 1 7 1.25 1 Week 1 (study day 1 to 7) 0.938
## 9 1 8 1.25 2 Week 2 (study day 8 to 14) 1.19
## 10 1 9 1.25 2 Week 2 (study day 8 to 14) 1.19
## 11 1 10 1.25 2 Week 2 (study day 8 to 14) 1.19
## 12 1 11 1.21 2 Week 2 (study day 8 to 14) 1.19
## 13 1 12 1.17 2 Week 2 (study day 8 to 14) 1.19
## 14 1 13 1.17 2 Week 2 (study day 8 to 14) 1.19
## 15 1 14 1.02 2 Week 2 (study day 8 to 14) 1.19
## 16 1 15 1.02 3 Week 3 (study day 15 to 21) 0.938
## 17 1 16 1.02 3 Week 3 (study day 15 to 21) 0.938
## 18 1 17 0.938 3 Week 3 (study day 15 to 21) 0.938
## 19 1 18 0.938 3 Week 3 (study day 15 to 21) 0.938
## 20 1 19 0.938 3 Week 3 (study day 15 to 21) 0.938
## 21 1 20 0.859 3 Week 3 (study day 15 to 21) 0.938
## 22 1 21 0.859 3 Week 3 (study day 15 to 21) 0.938
## 23 1 22 0.859 4 Week 4 (study day 22 to 28) 0.756
## 24 1 23 0.781 4 Week 4 (study day 22 to 28) 0.756
## 25 1 24 0.781 4 Week 4 (study day 22 to 28) 0.756
## 26 1 25 0.781 4 Week 4 (study day 22 to 28) 0.756
## 27 1 26 0.703 4 Week 4 (study day 22 to 28) 0.756
## 28 1 27 0.692 4 Week 4 (study day 22 to 28) 0.756
## 29 1 28 0.692 4 Week 4 (study day 22 to 28) 0.756
## 30 1 29 0.692 5 Week 5 (study day 29 to 35) 0.683
## 31 1 30 0.692 5 Week 5 (study day 29 to 35) 0.683
## 32 1 31 0.692 5 Week 5 (study day 29 to 35) 0.683
## 33 1 32 0.692 5 Week 5 (study day 29 to 35) 0.683
## 34 1 33 0.672 5 Week 5 (study day 29 to 35) 0.683
## 35 1 34 0.672 5 Week 5 (study day 29 to 35) 0.683
## 36 1 35 0.672 5 Week 5 (study day 29 to 35) 0.683
## 37 1 36 0.597 6 Week 6 (study day 36 to 42) 0.582
## 38 1 37 0.597 6 Week 6 (study day 36 to 42) 0.582
## 39 1 38 0.597 6 Week 6 (study day 36 to 42) 0.582
## 40 1 39 0.597 6 Week 6 (study day 36 to 42) 0.582
## 41 1 40 0.586 6 Week 6 (study day 36 to 42) 0.582
## 42 1 41 0.586 6 Week 6 (study day 36 to 42) 0.582
## 43 1 42 0.512 6 Week 6 (study day 36 to 42) 0.582
## 44 1 43 0.512 7 Week 7 (study day 43 to 49) 0.512
## 45 1 44 0.512 7 Week 7 (study day 43 to 49) 0.512
## 46 1 45 0.512 7 Week 7 (study day 43 to 49) 0.512
## 47 1 46 0.512 7 Week 7 (study day 43 to 49) 0.512
## 48 1 47 0.512 7 Week 7 (study day 43 to 49) 0.512
## 49 1 48 0.512 7 Week 7 (study day 43 to 49) 0.512
## 50 1 49 0.512 7 Week 7 (study day 43 to 49) 0.512
## 51 1 50 0.512 8 Week 8 (study day 50 to 56) 0.444
## 52 1 51 0.439 8 Week 8 (study day 50 to 56) 0.444
## 53 1 52 0.439 8 Week 8 (study day 50 to 56) 0.444
## 54 1 53 0.439 8 Week 8 (study day 50 to 56) 0.444
## 55 1 54 0.427 8 Week 8 (study day 50 to 56) 0.444
## 56 1 55 0.427 8 Week 8 (study day 50 to 56) 0.444
## 57 1 56 0.427 8 Week 8 (study day 50 to 56) 0.444
## 58 2 0 26.8 0 Baseline 26.8
## 59 2 1 2.39 1 Week 1 (study day 1 to 7) 16.7
## 60 2 2 27.4 1 Week 1 (study day 1 to 7) 16.7
## 61 2 3 27.4 1 Week 1 (study day 1 to 7) 16.7
## 62 2 4 27.4 1 Week 1 (study day 1 to 7) 16.7
## 63 2 5 26.6 1 Week 1 (study day 1 to 7) 16.7
## 64 2 6 2.66 1 Week 1 (study day 1 to 7) 16.7
## 65 2 7 3.19 1 Week 1 (study day 1 to 7) 16.7
## 66 2 8 3.19 2 Week 2 (study day 8 to 14) 2.93
## 67 2 9 3.19 2 Week 2 (study day 8 to 14) 2.93
## 68 2 10 2.93 2 Week 2 (study day 8 to 14) 2.93
## 69 2 11 2.93 2 Week 2 (study day 8 to 14) 2.93
## 70 2 12 2.93 2 Week 2 (study day 8 to 14) 2.93
## 71 2 13 2.66 2 Week 2 (study day 8 to 14) 2.93
## 72 2 14 2.66 2 Week 2 (study day 8 to 14) 2.93
## 73 2 15 2.66 3 Week 3 (study day 15 to 21) 2.51
## 74 2 16 2.66 3 Week 3 (study day 15 to 21) 2.51
## 75 2 17 2.66 3 Week 3 (study day 15 to 21) 2.51
## 76 2 18 2.39 3 Week 3 (study day 15 to 21) 2.51
## 77 2 19 2.39 3 Week 3 (study day 15 to 21) 2.51
## 78 2 20 2.39 3 Week 3 (study day 15 to 21) 2.51
## 79 2 21 2.39 3 Week 3 (study day 15 to 21) 2.51
## 80 2 22 2.39 4 Week 4 (study day 22 to 28) 2.05
## 81 2 23 2.13 4 Week 4 (study day 22 to 28) 2.05
## 82 2 24 2.13 4 Week 4 (study day 22 to 28) 2.05
## 83 2 25 2.13 4 Week 4 (study day 22 to 28) 2.05
## 84 2 26 2.13 4 Week 4 (study day 22 to 28) 2.05
## 85 2 27 1.73 4 Week 4 (study day 22 to 28) 2.05
## 86 2 28 1.73 4 Week 4 (study day 22 to 28) 2.05
## 87 2 29 1.73 5 Week 5 (study day 29 to 35) 1.65
## 88 2 30 1.73 5 Week 5 (study day 29 to 35) 1.65
## 89 2 31 1.73 5 Week 5 (study day 29 to 35) 1.65
## 90 2 32 1.60 5 Week 5 (study day 29 to 35) 1.65
## 91 2 33 1.60 5 Week 5 (study day 29 to 35) 1.65
## 92 2 34 1.60 5 Week 5 (study day 29 to 35) 1.65
## 93 2 35 1.60 5 Week 5 (study day 29 to 35) 1.65
## 94 2 36 1.60 6 Week 6 (study day 36 to 42) 1.59
## 95 2 37 1.60 6 Week 6 (study day 36 to 42) 1.59
## 96 2 38 1.70 6 Week 6 (study day 36 to 42) 1.59
## 97 2 39 1.56 6 Week 6 (study day 36 to 42) 1.59
## 98 2 40 1.56 6 Week 6 (study day 36 to 42) 1.59
## 99 2 41 1.56 6 Week 6 (study day 36 to 42) 1.59
## 100 2 42 1.56 6 Week 6 (study day 36 to 42) 1.59
## 101 2 43 1.48 7 Week 7 (study day 43 to 49) 1.27
## 102 2 44 1.25 7 Week 7 (study day 43 to 49) 1.27
## 103 2 45 1.25 7 Week 7 (study day 43 to 49) 1.27
## 104 2 46 1.25 7 Week 7 (study day 43 to 49) 1.27
## 105 2 47 1.25 7 Week 7 (study day 43 to 49) 1.27
## 106 2 48 1.25 7 Week 7 (study day 43 to 49) 1.27
## 107 2 49 1.14 7 Week 7 (study day 43 to 49) 1.27
## 108 2 50 1.14 8 Week 8 (study day 50 to 56) 1.09
## 109 2 51 1.14 8 Week 8 (study day 50 to 56) 1.09
## 110 2 52 1.14 8 Week 8 (study day 50 to 56) 1.09
## 111 2 53 1.14 8 Week 8 (study day 50 to 56) 1.09
## 112 2 54 1.02 8 Week 8 (study day 50 to 56) 1.09
## 113 2 55 1.02 8 Week 8 (study day 50 to 56) 1.09
## 114 2 56 1.02 8 Week 8 (study day 50 to 56) 1.09
## 115 3 0 2.5 0 Baseline 2.5
## 116 3 1 2.5 1 Week 1 (study day 1 to 7) 2.5
## 117 3 2 2.5 1 Week 1 (study day 1 to 7) 2.5
## 118 3 3 2.5 1 Week 1 (study day 1 to 7) 2.5
## 119 3 4 2.5 1 Week 1 (study day 1 to 7) 2.5
## 120 3 5 2.5 1 Week 1 (study day 1 to 7) 2.5
## 121 3 6 2.5 1 Week 1 (study day 1 to 7) 2.5
## 122 3 7 2.5 1 Week 1 (study day 1 to 7) 2.5
## 123 3 8 2.5 2 Week 2 (study day 8 to 14) 2.44
## 124 3 9 2.51 2 Week 2 (study day 8 to 14) 2.44
## 125 3 10 2.51 2 Week 2 (study day 8 to 14) 2.44
## 126 3 11 2.51 2 Week 2 (study day 8 to 14) 2.44
## 127 3 12 2.51 2 Week 2 (study day 8 to 14) 2.44
## 128 3 13 2.51 2 Week 2 (study day 8 to 14) 2.44
## 129 3 14 2.01 2 Week 2 (study day 8 to 14) 2.44
## 130 3 15 2.01 3 Week 3 (study day 15 to 21) 1.90
## 131 3 16 2.01 3 Week 3 (study day 15 to 21) 1.90
## 132 3 17 2.01 3 Week 3 (study day 15 to 21) 1.90
## 133 3 18 2.01 3 Week 3 (study day 15 to 21) 1.90
## 134 3 19 1.76 3 Week 3 (study day 15 to 21) 1.90
## 135 3 20 1.76 3 Week 3 (study day 15 to 21) 1.90
## 136 3 21 1.76 3 Week 3 (study day 15 to 21) 1.90
## 137 3 22 1.51 4 Week 4 (study day 22 to 28) 1.33
## 138 3 23 1.51 4 Week 4 (study day 22 to 28) 1.33
## 139 3 24 1.51 4 Week 4 (study day 22 to 28) 1.33
## 140 3 25 1.26 4 Week 4 (study day 22 to 28) 1.33
## 141 3 26 1.26 4 Week 4 (study day 22 to 28) 1.33
## 142 3 27 1.26 4 Week 4 (study day 22 to 28) 1.33
## 143 3 28 1.01 4 Week 4 (study day 22 to 28) 1.33
## 144 3 29 1.01 5 Week 5 (study day 29 to 35) 0.824
## 145 3 30 0.806 5 Week 5 (study day 29 to 35) 0.824
## 146 3 31 0.806 5 Week 5 (study day 29 to 35) 0.824
## 147 3 32 0.806 5 Week 5 (study day 29 to 35) 0.824
## 148 3 33 0.781 5 Week 5 (study day 29 to 35) 0.824
## 149 3 34 0.781 5 Week 5 (study day 29 to 35) 0.824
## 150 3 35 0.781 5 Week 5 (study day 29 to 35) 0.824
## 151 3 36 0.781 6 Week 6 (study day 36 to 42) 0.776
## 152 3 37 0.781 6 Week 6 (study day 36 to 42) 0.776
## 153 3 38 0.781 6 Week 6 (study day 36 to 42) 0.776
## 154 3 39 0.781 6 Week 6 (study day 36 to 42) 0.776
## 155 3 40 0.769 6 Week 6 (study day 36 to 42) 0.776
## 156 3 41 0.769 6 Week 6 (study day 36 to 42) 0.776
## 157 3 42 0.769 6 Week 6 (study day 36 to 42) 0.776
## 158 3 43 0.769 7 Week 7 (study day 43 to 49) 0.604
## 159 3 44 0.577 7 Week 7 (study day 43 to 49) 0.604
## 160 3 45 0.577 7 Week 7 (study day 43 to 49) 0.604
## 161 3 46 0.577 7 Week 7 (study day 43 to 49) 0.604
## 162 3 47 0.577 7 Week 7 (study day 43 to 49) 0.604
## 163 3 48 0.577 7 Week 7 (study day 43 to 49) 0.604
## 164 3 49 0.577 7 Week 7 (study day 43 to 49) 0.604
## 165 3 50 0.577 8 Week 8 (study day 50 to 56) 0.412
## 166 3 51 0.385 8 Week 8 (study day 50 to 56) 0.412
## 167 3 52 0.385 8 Week 8 (study day 50 to 56) 0.412
## 168 3 53 0.385 8 Week 8 (study day 50 to 56) 0.412
## 169 3 54 0.385 8 Week 8 (study day 50 to 56) 0.412
## 170 3 55 0.385 8 Week 8 (study day 50 to 56) 0.412
## 171 3 56 0.385 8 Week 8 (study day 50 to 56) 0.412
## 172 4 0 25.5 0 Baseline 25.5
## 173 4 1 25.5 1 Week 1 (study day 1 to 7) 13.3
## 174 4 2 25.5 1 Week 1 (study day 1 to 7) 13.3
## 175 4 3 26.8 1 Week 1 (study day 1 to 7) 13.3
## 176 4 4 3.83 1 Week 1 (study day 1 to 7) 13.3
## 177 4 5 3.83 1 Week 1 (study day 1 to 7) 13.3
## 178 4 6 3.83 1 Week 1 (study day 1 to 7) 13.3
## 179 4 7 3.83 1 Week 1 (study day 1 to 7) 13.3
## 180 4 8 3.83 2 Week 2 (study day 8 to 14) 3.72
## 181 4 9 3.83 2 Week 2 (study day 8 to 14) 3.72
## 182 4 10 3.83 2 Week 2 (study day 8 to 14) 3.72
## 183 4 11 3.83 2 Week 2 (study day 8 to 14) 3.72
## 184 4 12 3.57 2 Week 2 (study day 8 to 14) 3.72
## 185 4 13 3.57 2 Week 2 (study day 8 to 14) 3.72
## 186 4 14 3.57 2 Week 2 (study day 8 to 14) 3.72
## 187 4 15 3.19 3 Week 3 (study day 15 to 21) 2.93
## 188 4 16 3.19 3 Week 3 (study day 15 to 21) 2.93
## 189 4 17 3.19 3 Week 3 (study day 15 to 21) 2.93
## 190 4 18 2.81 3 Week 3 (study day 15 to 21) 2.93
## 191 4 19 2.81 3 Week 3 (study day 15 to 21) 2.93
## 192 4 20 2.81 3 Week 3 (study day 15 to 21) 2.93
## 193 4 21 2.55 3 Week 3 (study day 15 to 21) 2.93
## 194 4 22 2.55 4 Week 4 (study day 22 to 28) 2.30
## 195 4 23 2.55 4 Week 4 (study day 22 to 28) 2.30
## 196 4 24 2.30 4 Week 4 (study day 22 to 28) 2.30
## 197 4 25 2.30 4 Week 4 (study day 22 to 28) 2.30
## 198 4 26 2.30 4 Week 4 (study day 22 to 28) 2.30
## 199 4 27 2.04 4 Week 4 (study day 22 to 28) 2.30
## 200 4 28 2.04 4 Week 4 (study day 22 to 28) 2.30
## 201 4 29 2.04 5 Week 5 (study day 29 to 35) 1.71
## 202 4 30 1.79 5 Week 5 (study day 29 to 35) 1.71
## 203 4 31 1.79 5 Week 5 (study day 29 to 35) 1.71
## 204 4 32 1.79 5 Week 5 (study day 29 to 35) 1.71
## 205 4 33 1.53 5 Week 5 (study day 29 to 35) 1.71
## 206 4 34 1.53 5 Week 5 (study day 29 to 35) 1.71
## 207 4 35 1.53 5 Week 5 (study day 29 to 35) 1.71
## 208 4 36 1.28 6 Week 6 (study day 36 to 42) 1.28
## 209 4 37 1.28 6 Week 6 (study day 36 to 42) 1.28
## 210 4 38 1.28 6 Week 6 (study day 36 to 42) 1.28
## 211 4 39 1.28 6 Week 6 (study day 36 to 42) 1.28
## 212 4 40 1.28 6 Week 6 (study day 36 to 42) 1.28
## 213 4 41 1.28 6 Week 6 (study day 36 to 42) 1.28
## 214 4 42 1.28 6 Week 6 (study day 36 to 42) 1.28
## 215 4 43 1.28 7 Week 7 (study day 43 to 49) 1.15
## 216 4 44 1.20 7 Week 7 (study day 43 to 49) 1.15
## 217 4 45 1.20 7 Week 7 (study day 43 to 49) 1.15
## 218 4 46 1.20 7 Week 7 (study day 43 to 49) 1.15
## 219 4 47 1.06 7 Week 7 (study day 43 to 49) 1.15
## 220 4 48 1.06 7 Week 7 (study day 43 to 49) 1.15
## 221 4 49 1.06 7 Week 7 (study day 43 to 49) 1.15
## 222 4 50 1.06 8 Week 8 (study day 50 to 56) 1.06
## 223 4 51 1.06 8 Week 8 (study day 50 to 56) 1.06
## 224 4 52 1.06 8 Week 8 (study day 50 to 56) 1.06
## 225 4 53 1.06 8 Week 8 (study day 50 to 56) 1.06
## 226 4 54 1.06 8 Week 8 (study day 50 to 56) 1.06
## 227 4 55 1.06 8 Week 8 (study day 50 to 56) 1.06
## 228 4 56 1.06 8 Week 8 (study day 50 to 56) 1.06
## 229 5 0 2.98 0 Baseline 2.98
## 230 5 1 2.38 1 Week 1 (study day 1 to 7) 2.10
## 231 5 2 2.38 1 Week 1 (study day 1 to 7) 2.10
## 232 5 3 1.98 1 Week 1 (study day 1 to 7) 2.10
## 233 5 4 1.98 1 Week 1 (study day 1 to 7) 2.10
## 234 5 5 1.98 1 Week 1 (study day 1 to 7) 2.10
## 235 5 6 1.98 1 Week 1 (study day 1 to 7) 2.10
## 236 5 7 1.98 1 Week 1 (study day 1 to 7) 2.10
## 237 5 8 1.98 2 Week 2 (study day 8 to 14) 1.81
## 238 5 9 1.98 2 Week 2 (study day 8 to 14) 1.81
## 239 5 10 1.79 2 Week 2 (study day 8 to 14) 1.81
## 240 5 11 1.79 2 Week 2 (study day 8 to 14) 1.81
## 241 5 12 1.79 2 Week 2 (study day 8 to 14) 1.81
## 242 5 13 1.79 2 Week 2 (study day 8 to 14) 1.81
## 243 5 14 1.59 2 Week 2 (study day 8 to 14) 1.81
## 244 5 15 1.59 3 Week 3 (study day 15 to 21) 1.33
## 245 5 16 1.39 3 Week 3 (study day 15 to 21) 1.33
## 246 5 17 1.39 3 Week 3 (study day 15 to 21) 1.33
## 247 5 18 1.39 3 Week 3 (study day 15 to 21) 1.33
## 248 5 19 1.19 3 Week 3 (study day 15 to 21) 1.33
## 249 5 20 1.19 3 Week 3 (study day 15 to 21) 1.33
## 250 5 21 1.19 3 Week 3 (study day 15 to 21) 1.33
## 251 5 22 1.09 4 Week 4 (study day 22 to 28) 0.964
## 252 5 23 1.09 4 Week 4 (study day 22 to 28) 0.964
## 253 5 24 1.09 4 Week 4 (study day 22 to 28) 0.964
## 254 5 25 1.09 4 Week 4 (study day 22 to 28) 0.964
## 255 5 26 0.794 4 Week 4 (study day 22 to 28) 0.964
## 256 5 27 0.794 4 Week 4 (study day 22 to 28) 0.964
## 257 5 28 0.794 4 Week 4 (study day 22 to 28) 0.964
## 258 5 29 0.781 5 Week 5 (study day 29 to 35) 0.580
## 259 5 30 0.625 5 Week 5 (study day 29 to 35) 0.580
## 260 5 31 0.625 5 Week 5 (study day 29 to 35) 0.580
## 261 5 32 0.625 5 Week 5 (study day 29 to 35) 0.580
## 262 5 33 0.469 5 Week 5 (study day 29 to 35) 0.580
## 263 5 34 0.469 5 Week 5 (study day 29 to 35) 0.580
## 264 5 35 0.469 5 Week 5 (study day 29 to 35) 0.580
## 265 5 36 0.469 6 Week 6 (study day 36 to 42) 0.413
## 266 5 37 0.469 6 Week 6 (study day 36 to 42) 0.413
## 267 5 38 0.391 6 Week 6 (study day 36 to 42) 0.413
## 268 5 39 0.391 6 Week 6 (study day 36 to 42) 0.413
## 269 5 40 0.391 6 Week 6 (study day 36 to 42) 0.413
## 270 5 41 0.391 6 Week 6 (study day 36 to 42) 0.413
## 271 5 42 0.391 6 Week 6 (study day 36 to 42) 0.413
## 272 5 43 0.391 7 Week 7 (study day 43 to 49) 0.332
## 273 5 44 0.391 7 Week 7 (study day 43 to 49) 0.332
## 274 5 45 0.312 7 Week 7 (study day 43 to 49) 0.332
## 275 5 46 0.312 7 Week 7 (study day 43 to 49) 0.332
## 276 5 47 0.312 7 Week 7 (study day 43 to 49) 0.332
## 277 5 48 0.303 7 Week 7 (study day 43 to 49) 0.332
## 278 5 49 0.303 7 Week 7 (study day 43 to 49) 0.332
## 279 5 50 0.303 8 Week 8 (study day 50 to 56) 0.249
## 280 5 51 0.303 8 Week 8 (study day 50 to 56) 0.249
## 281 5 52 0.227 8 Week 8 (study day 50 to 56) 0.249
## 282 5 53 0.227 8 Week 8 (study day 50 to 56) 0.249
## 283 5 54 0.227 8 Week 8 (study day 50 to 56) 0.249
## 284 5 55 0.227 8 Week 8 (study day 50 to 56) 0.249
## 285 5 56 0.227 8 Week 8 (study day 50 to 56) 0.249
## 286 6 0 37.5 0 Baseline 37.5
## 287 6 1 17.9 1 Week 1 (study day 1 to 7) 15.3
## 288 6 2 18.3 1 Week 1 (study day 1 to 7) 15.3
## 289 6 3 11.7 1 Week 1 (study day 1 to 7) 15.3
## 290 6 4 15 1 Week 1 (study day 1 to 7) 15.3
## 291 6 5 18.3 1 Week 1 (study day 1 to 7) 15.3
## 292 6 6 15 1 Week 1 (study day 1 to 7) 15.3
## 293 6 7 11 1 Week 1 (study day 1 to 7) 15.3
## 294 6 8 15 2 Week 2 (study day 8 to 14) 6.64
## 295 6 9 13.3 2 Week 2 (study day 8 to 14) 6.64
## 296 6 10 5 2 Week 2 (study day 8 to 14) 6.64
## 297 6 11 2.75 2 Week 2 (study day 8 to 14) 6.64
## 298 6 12 4.58 2 Week 2 (study day 8 to 14) 6.64
## 299 6 13 3.33 2 Week 2 (study day 8 to 14) 6.64
## 300 6 14 2.5 2 Week 2 (study day 8 to 14) 6.64
## 301 6 15 2.5 3 Week 3 (study day 15 to 21) 2.5
## 302 6 16 2.5 3 Week 3 (study day 15 to 21) 2.5
## 303 6 17 2.5 3 Week 3 (study day 15 to 21) 2.5
## 304 6 18 2.5 3 Week 3 (study day 15 to 21) 2.5
## 305 6 19 2.5 3 Week 3 (study day 15 to 21) 2.5
## 306 6 20 2.5 3 Week 3 (study day 15 to 21) 2.5
## 307 6 21 2.5 3 Week 3 (study day 15 to 21) 2.5
## 308 6 22 2.5 4 Week 4 (study day 22 to 28) 2.32
## 309 6 23 2.5 4 Week 4 (study day 22 to 28) 2.32
## 310 6 24 2.5 4 Week 4 (study day 22 to 28) 2.32
## 311 6 25 2.5 4 Week 4 (study day 22 to 28) 2.32
## 312 6 26 2.08 4 Week 4 (study day 22 to 28) 2.32
## 313 6 27 2.08 4 Week 4 (study day 22 to 28) 2.32
## 314 6 28 2.08 4 Week 4 (study day 22 to 28) 2.32
## 315 6 29 1.88 5 Week 5 (study day 29 to 35) 1.73
## 316 6 30 1.88 5 Week 5 (study day 29 to 35) 1.73
## 317 6 31 1.88 5 Week 5 (study day 29 to 35) 1.73
## 318 6 32 1.67 5 Week 5 (study day 29 to 35) 1.73
## 319 6 33 1.67 5 Week 5 (study day 29 to 35) 1.73
## 320 6 34 1.67 5 Week 5 (study day 29 to 35) 1.73
## 321 6 35 1.46 5 Week 5 (study day 29 to 35) 1.73
## 322 6 36 1.46 6 Week 6 (study day 36 to 42) 1.34
## 323 6 37 1.46 6 Week 6 (study day 36 to 42) 1.34
## 324 6 38 1.46 6 Week 6 (study day 36 to 42) 1.34
## 325 6 39 1.25 6 Week 6 (study day 36 to 42) 1.34
## 326 6 40 1.25 6 Week 6 (study day 36 to 42) 1.34
## 327 6 41 1.25 6 Week 6 (study day 36 to 42) 1.34
## 328 6 42 1.25 6 Week 6 (study day 36 to 42) 1.34
## 329 6 43 1.45 7 Week 7 (study day 43 to 49) 1.18
## 330 6 44 1.21 7 Week 7 (study day 43 to 49) 1.18
## 331 6 45 1.21 7 Week 7 (study day 43 to 49) 1.18
## 332 6 46 1.21 7 Week 7 (study day 43 to 49) 1.18
## 333 6 47 1.21 7 Week 7 (study day 43 to 49) 1.18
## 334 6 48 0.969 7 Week 7 (study day 43 to 49) 1.18
## 335 6 49 0.969 7 Week 7 (study day 43 to 49) 1.18
## 336 6 50 0.969 8 Week 8 (study day 50 to 56) 0.796
## 337 6 51 0.969 8 Week 8 (study day 50 to 56) 0.796
## 338 6 52 0.727 8 Week 8 (study day 50 to 56) 0.796
## 339 6 53 0.727 8 Week 8 (study day 50 to 56) 0.796
## 340 6 54 0.727 8 Week 8 (study day 50 to 56) 0.796
## 341 6 55 0.727 8 Week 8 (study day 50 to 56) 0.796
## 342 6 56 0.727 8 Week 8 (study day 50 to 56) 0.796
## 343 7 0 6.34 0 Baseline 6.34
## 344 7 1 4.39 1 Week 1 (study day 1 to 7) 2.73
## 345 7 2 3.90 1 Week 1 (study day 1 to 7) 2.73
## 346 7 3 2.92 1 Week 1 (study day 1 to 7) 2.73
## 347 7 4 2.44 1 Week 1 (study day 1 to 7) 2.73
## 348 7 5 2.19 1 Week 1 (study day 1 to 7) 2.73
## 349 7 6 1.83 1 Week 1 (study day 1 to 7) 2.73
## 350 7 7 1.46 1 Week 1 (study day 1 to 7) 2.73
## 351 7 8 1.46 2 Week 2 (study day 8 to 14) 1.36
## 352 7 9 1.46 2 Week 2 (study day 8 to 14) 1.36
## 353 7 10 1.46 2 Week 2 (study day 8 to 14) 1.36
## 354 7 11 1.46 2 Week 2 (study day 8 to 14) 1.36
## 355 7 12 1.22 2 Week 2 (study day 8 to 14) 1.36
## 356 7 13 1.22 2 Week 2 (study day 8 to 14) 1.36
## 357 7 14 1.22 2 Week 2 (study day 8 to 14) 1.36
## 358 7 15 1.22 3 Week 3 (study day 15 to 21) 1.13
## 359 7 16 1.22 3 Week 3 (study day 15 to 21) 1.13
## 360 7 17 1.22 3 Week 3 (study day 15 to 21) 1.13
## 361 7 18 1.22 3 Week 3 (study day 15 to 21) 1.13
## 362 7 19 1.12 3 Week 3 (study day 15 to 21) 1.13
## 363 7 20 0.975 3 Week 3 (study day 15 to 21) 1.13
## 364 7 21 0.975 3 Week 3 (study day 15 to 21) 1.13
## 365 7 22 0.780 4 Week 4 (study day 22 to 28) 0.696
## 366 7 23 0.780 4 Week 4 (study day 22 to 28) 0.696
## 367 7 24 0.780 4 Week 4 (study day 22 to 28) 0.696
## 368 7 25 0.780 4 Week 4 (study day 22 to 28) 0.696
## 369 7 26 0.585 4 Week 4 (study day 22 to 28) 0.696
## 370 7 27 0.585 4 Week 4 (study day 22 to 28) 0.696
## 371 7 28 0.585 4 Week 4 (study day 22 to 28) 0.696
## 372 7 29 0.585 5 Week 5 (study day 29 to 35) 0.501
## 373 7 30 0.487 5 Week 5 (study day 29 to 35) 0.501
## 374 7 31 0.487 5 Week 5 (study day 29 to 35) 0.501
## 375 7 32 0.487 5 Week 5 (study day 29 to 35) 0.501
## 376 7 33 0.487 5 Week 5 (study day 29 to 35) 0.501
## 377 7 34 0.487 5 Week 5 (study day 29 to 35) 0.501
## 378 7 35 0.487 5 Week 5 (study day 29 to 35) 0.501
## 379 7 36 0.487 6 Week 6 (study day 36 to 42) 0.459
## 380 7 37 0.487 6 Week 6 (study day 36 to 42) 0.459
## 381 7 38 0.487 6 Week 6 (study day 36 to 42) 0.459
## 382 7 39 0.487 6 Week 6 (study day 36 to 42) 0.459
## 383 7 40 0.487 6 Week 6 (study day 36 to 42) 0.459
## 384 7 41 0.390 6 Week 6 (study day 36 to 42) 0.459
## 385 7 42 0.390 6 Week 6 (study day 36 to 42) 0.459
## 386 7 43 0.390 7 Week 7 (study day 43 to 49) 0.376
## 387 7 44 0.390 7 Week 7 (study day 43 to 49) 0.376
## 388 7 45 0.390 7 Week 7 (study day 43 to 49) 0.376
## 389 7 46 0.390 7 Week 7 (study day 43 to 49) 0.376
## 390 7 47 0.390 7 Week 7 (study day 43 to 49) 0.376
## 391 7 48 0.390 7 Week 7 (study day 43 to 49) 0.376
## 392 7 49 0.292 7 Week 7 (study day 43 to 49) 0.376
## 393 7 50 0.292 8 Week 8 (study day 50 to 56) 0.292
## 394 7 51 0.292 8 Week 8 (study day 50 to 56) 0.292
## 395 7 52 0.292 8 Week 8 (study day 50 to 56) 0.292
## 396 7 53 0.292 8 Week 8 (study day 50 to 56) 0.292
## 397 7 54 0.292 8 Week 8 (study day 50 to 56) 0.292
## 398 7 55 0.292 8 Week 8 (study day 50 to 56) 0.292
## 399 7 56 0.292 8 Week 8 (study day 50 to 56) 0.292
## 400 8 0 1.82 0 Baseline 1.82
## 401 8 1 1.45 1 Week 1 (study day 1 to 7) 0.851
## 402 8 2 1.27 1 Week 1 (study day 1 to 7) 0.851
## 403 8 3 1.09 1 Week 1 (study day 1 to 7) 0.851
## 404 8 4 0.727 1 Week 1 (study day 1 to 7) 0.851
## 405 8 5 0.545 1 Week 1 (study day 1 to 7) 0.851
## 406 8 6 0.436 1 Week 1 (study day 1 to 7) 0.851
## 407 8 7 0.436 1 Week 1 (study day 1 to 7) 0.851
## 408 8 8 0.436 2 Week 2 (study day 8 to 14) 0.426
## 409 8 9 0.436 2 Week 2 (study day 8 to 14) 0.426
## 410 8 10 0.436 2 Week 2 (study day 8 to 14) 0.426
## 411 8 11 0.436 2 Week 2 (study day 8 to 14) 0.426
## 412 8 12 0.436 2 Week 2 (study day 8 to 14) 0.426
## 413 8 13 0.436 2 Week 2 (study day 8 to 14) 0.426
## 414 8 14 0.363 2 Week 2 (study day 8 to 14) 0.426
## 415 8 15 0.363 3 Week 3 (study day 15 to 21) 0.369
## 416 8 16 0.368 3 Week 3 (study day 15 to 21) 0.369
## 417 8 17 0.368 3 Week 3 (study day 15 to 21) 0.369
## 418 8 18 0.368 3 Week 3 (study day 15 to 21) 0.369
## 419 8 19 0.368 3 Week 3 (study day 15 to 21) 0.369
## 420 8 20 0.368 3 Week 3 (study day 15 to 21) 0.369
## 421 8 21 0.383 3 Week 3 (study day 15 to 21) 0.369
## 422 8 22 0.383 4 Week 4 (study day 22 to 28) 0.314
## 423 8 23 0.307 4 Week 4 (study day 22 to 28) 0.314
## 424 8 24 0.303 4 Week 4 (study day 22 to 28) 0.314
## 425 8 25 0.303 4 Week 4 (study day 22 to 28) 0.314
## 426 8 26 0.303 4 Week 4 (study day 22 to 28) 0.314
## 427 8 27 0.303 4 Week 4 (study day 22 to 28) 0.314
## 428 8 28 0.297 4 Week 4 (study day 22 to 28) 0.314
## 429 8 29 0.297 5 Week 5 (study day 29 to 35) 0.297
## 430 8 30 0.297 5 Week 5 (study day 29 to 35) 0.297
## 431 8 31 0.297 5 Week 5 (study day 29 to 35) 0.297
## 432 8 32 0.297 5 Week 5 (study day 29 to 35) 0.297
## 433 8 33 0.297 5 Week 5 (study day 29 to 35) 0.297
## 434 8 34 0.297 5 Week 5 (study day 29 to 35) 0.297
## 435 8 35 0.294 5 Week 5 (study day 29 to 35) 0.297
## 436 8 36 0.294 6 Week 6 (study day 36 to 42) 0.294
## 437 8 37 0.294 6 Week 6 (study day 36 to 42) 0.294
## 438 8 38 0.294 6 Week 6 (study day 36 to 42) 0.294
## 439 8 39 0.294 6 Week 6 (study day 36 to 42) 0.294
## 440 8 40 0.294 6 Week 6 (study day 36 to 42) 0.294
## 441 8 41 0.294 6 Week 6 (study day 36 to 42) 0.294
## 442 8 42 0.296 6 Week 6 (study day 36 to 42) 0.294
## 443 8 43 0.296 7 Week 7 (study day 43 to 49) 0.269
## 444 8 44 0.296 7 Week 7 (study day 43 to 49) 0.269
## 445 8 45 0.259 7 Week 7 (study day 43 to 49) 0.269
## 446 8 46 0.259 7 Week 7 (study day 43 to 49) 0.269
## 447 8 47 0.259 7 Week 7 (study day 43 to 49) 0.269
## 448 8 48 0.257 7 Week 7 (study day 43 to 49) 0.269
## 449 8 49 0.257 7 Week 7 (study day 43 to 49) 0.269
## 450 8 50 0.257 8 Week 8 (study day 50 to 56) 0.255
## 451 8 51 0.257 8 Week 8 (study day 50 to 56) 0.255
## 452 8 52 0.257 8 Week 8 (study day 50 to 56) 0.255
## 453 8 53 0.257 8 Week 8 (study day 50 to 56) 0.255
## 454 8 54 0.257 8 Week 8 (study day 50 to 56) 0.255
## 455 8 55 0.252 8 Week 8 (study day 50 to 56) 0.255
## 456 8 56 0.252 8 Week 8 (study day 50 to 56) 0.255
## 457 9 0 36.4 0 Baseline 36.4
## 458 9 1 36.4 1 Week 1 (study day 1 to 7) 6.86
## 459 9 2 1.94 1 Week 1 (study day 1 to 7) 6.86
## 460 9 3 1.94 1 Week 1 (study day 1 to 7) 6.86
## 461 9 4 1.94 1 Week 1 (study day 1 to 7) 6.86
## 462 9 5 1.94 1 Week 1 (study day 1 to 7) 6.86
## 463 9 6 1.91 1 Week 1 (study day 1 to 7) 6.86
## 464 9 7 1.91 1 Week 1 (study day 1 to 7) 6.86
## 465 9 8 1.91 2 Week 2 (study day 8 to 14) 1.88
## 466 9 9 1.94 2 Week 2 (study day 8 to 14) 1.88
## 467 9 10 1.94 2 Week 2 (study day 8 to 14) 1.88
## 468 9 11 1.94 2 Week 2 (study day 8 to 14) 1.88
## 469 9 12 1.80 2 Week 2 (study day 8 to 14) 1.88
## 470 9 13 1.80 2 Week 2 (study day 8 to 14) 1.88
## 471 9 14 1.80 2 Week 2 (study day 8 to 14) 1.88
## 472 9 15 1.79 3 Week 3 (study day 15 to 21) 1.70
## 473 9 16 1.79 3 Week 3 (study day 15 to 21) 1.70
## 474 9 17 1.79 3 Week 3 (study day 15 to 21) 1.70
## 475 9 18 1.63 3 Week 3 (study day 15 to 21) 1.70
## 476 9 19 1.63 3 Week 3 (study day 15 to 21) 1.70
## 477 9 20 1.63 3 Week 3 (study day 15 to 21) 1.70
## 478 9 21 1.64 3 Week 3 (study day 15 to 21) 1.70
## 479 9 22 1.64 4 Week 4 (study day 22 to 28) 1.60
## 480 9 23 1.64 4 Week 4 (study day 22 to 28) 1.60
## 481 9 24 1.64 4 Week 4 (study day 22 to 28) 1.60
## 482 9 25 1.55 4 Week 4 (study day 22 to 28) 1.60
## 483 9 26 1.55 4 Week 4 (study day 22 to 28) 1.60
## 484 9 27 1.55 4 Week 4 (study day 22 to 28) 1.60
## 485 9 28 1.63 4 Week 4 (study day 22 to 28) 1.60
## 486 9 29 1.63 5 Week 5 (study day 29 to 35) 1.56
## 487 9 30 1.63 5 Week 5 (study day 29 to 35) 1.56
## 488 9 31 1.63 5 Week 5 (study day 29 to 35) 1.56
## 489 9 32 1.63 5 Week 5 (study day 29 to 35) 1.56
## 490 9 33 1.48 5 Week 5 (study day 29 to 35) 1.56
## 491 9 34 1.48 5 Week 5 (study day 29 to 35) 1.56
## 492 9 35 1.48 5 Week 5 (study day 29 to 35) 1.56
## 493 9 36 1.39 6 Week 6 (study day 36 to 42) 1.39
## 494 9 37 1.39 6 Week 6 (study day 36 to 42) 1.39
## 495 9 38 1.39 6 Week 6 (study day 36 to 42) 1.39
## 496 9 39 1.39 6 Week 6 (study day 36 to 42) 1.39
## 497 9 40 1.39 6 Week 6 (study day 36 to 42) 1.39
## 498 9 41 1.39 6 Week 6 (study day 36 to 42) 1.39
## 499 9 42 1.39 6 Week 6 (study day 36 to 42) 1.39
## 500 9 43 1.39 7 Week 7 (study day 43 to 49) 1.27
## 501 9 44 1.39 7 Week 7 (study day 43 to 49) 1.27
## 502 9 45 1.25 7 Week 7 (study day 43 to 49) 1.27
## 503 9 46 1.25 7 Week 7 (study day 43 to 49) 1.27
## 504 9 47 1.20 7 Week 7 (study day 43 to 49) 1.27
## 505 9 48 1.20 7 Week 7 (study day 43 to 49) 1.27
## 506 9 49 1.20 7 Week 7 (study day 43 to 49) 1.27
## 507 9 50 1.20 8 Week 8 (study day 50 to 56) 1.08
## 508 9 51 1.06 8 Week 8 (study day 50 to 56) 1.08
## 509 9 52 1.06 8 Week 8 (study day 50 to 56) 1.08
## 510 9 53 1.06 8 Week 8 (study day 50 to 56) 1.08
## 511 9 54 1.05 8 Week 8 (study day 50 to 56) 1.08
## 512 9 55 1.05 8 Week 8 (study day 50 to 56) 1.08
## 513 9 56 1.05 8 Week 8 (study day 50 to 56) 1.08
## 514 10 0 2.15 0 Baseline 2.15
## 515 10 1 2.15 1 Week 1 (study day 1 to 7) 16.5
## 516 10 2 2.15 1 Week 1 (study day 1 to 7) 16.5
## 517 10 3 2.15 1 Week 1 (study day 1 to 7) 16.5
## 518 10 4 2.15 1 Week 1 (study day 1 to 7) 16.5
## 519 10 5 36.3 1 Week 1 (study day 1 to 7) 16.5
## 520 10 6 35.2 1 Week 1 (study day 1 to 7) 16.5
## 521 10 7 35.2 1 Week 1 (study day 1 to 7) 16.5
## 522 10 8 2.07 2 Week 2 (study day 8 to 14) 2.19
## 523 10 9 2.07 2 Week 2 (study day 8 to 14) 2.19
## 524 10 10 2.33 2 Week 2 (study day 8 to 14) 2.19
## 525 10 11 2.10 2 Week 2 (study day 8 to 14) 2.19
## 526 10 12 2.19 2 Week 2 (study day 8 to 14) 2.19
## 527 10 13 2.29 2 Week 2 (study day 8 to 14) 2.19
## 528 10 14 2.29 2 Week 2 (study day 8 to 14) 2.19
## 529 10 15 2.29 3 Week 3 (study day 15 to 21) 1.47
## 530 10 16 2.29 3 Week 3 (study day 15 to 21) 1.47
## 531 10 17 1.15 3 Week 3 (study day 15 to 21) 1.47
## 532 10 18 1.15 3 Week 3 (study day 15 to 21) 1.47
## 533 10 19 1.15 3 Week 3 (study day 15 to 21) 1.47
## 534 10 20 1.15 3 Week 3 (study day 15 to 21) 1.47
## 535 10 21 1.15 3 Week 3 (study day 15 to 21) 1.47
## 536 10 22 1.15 4 Week 4 (study day 22 to 28) 1.13
## 537 10 23 1.13 4 Week 4 (study day 22 to 28) 1.13
## 538 10 24 1.13 4 Week 4 (study day 22 to 28) 1.13
## 539 10 25 1.13 4 Week 4 (study day 22 to 28) 1.13
## 540 10 26 1.13 4 Week 4 (study day 22 to 28) 1.13
## 541 10 27 1.13 4 Week 4 (study day 22 to 28) 1.13
## 542 10 28 1.13 4 Week 4 (study day 22 to 28) 1.13
## 543 10 29 1.13 5 Week 5 (study day 29 to 35) 1.12
## 544 10 30 1.12 5 Week 5 (study day 29 to 35) 1.12
## 545 10 31 1.12 5 Week 5 (study day 29 to 35) 1.12
## 546 10 32 1.12 5 Week 5 (study day 29 to 35) 1.12
## 547 10 33 1.12 5 Week 5 (study day 29 to 35) 1.12
## 548 10 34 1.12 5 Week 5 (study day 29 to 35) 1.12
## 549 10 35 1.12 5 Week 5 (study day 29 to 35) 1.12
## 550 10 36 1.12 6 Week 6 (study day 36 to 42) 1.11
## 551 10 37 1.12 6 Week 6 (study day 36 to 42) 1.11
## 552 10 38 1.12 6 Week 6 (study day 36 to 42) 1.11
## 553 10 39 1.10 6 Week 6 (study day 36 to 42) 1.11
## 554 10 40 1.10 6 Week 6 (study day 36 to 42) 1.11
## 555 10 41 1.10 6 Week 6 (study day 36 to 42) 1.11
## 556 10 42 1.10 6 Week 6 (study day 36 to 42) 1.11
## 557 10 43 1.10 7 Week 7 (study day 43 to 49) 0.786
## 558 10 44 0.735 7 Week 7 (study day 43 to 49) 0.786
## 559 10 45 0.735 7 Week 7 (study day 43 to 49) 0.786
## 560 10 46 0.735 7 Week 7 (study day 43 to 49) 0.786
## 561 10 47 0.735 7 Week 7 (study day 43 to 49) 0.786
## 562 10 48 0.735 7 Week 7 (study day 43 to 49) 0.786
## 563 10 49 0.719 7 Week 7 (study day 43 to 49) 0.786
## 564 10 50 0.719 8 Week 8 (study day 50 to 56) 0.462
## 565 10 51 0.719 8 Week 8 (study day 50 to 56) 0.462
## 566 10 52 0.360 8 Week 8 (study day 50 to 56) 0.462
## 567 10 53 0.360 8 Week 8 (study day 50 to 56) 0.462
## 568 10 54 0.360 8 Week 8 (study day 50 to 56) 0.462
## 569 10 55 0.360 8 Week 8 (study day 50 to 56) 0.462
## 570 10 56 0.360 8 Week 8 (study day 50 to 56) 0.462
## 571 11 0 25 0 Baseline 25
## 572 11 1 24.6 1 Week 1 (study day 1 to 7) 12.0
## 573 11 2 1.48 1 Week 1 (study day 1 to 7) 12.0
## 574 11 3 1.56 1 Week 1 (study day 1 to 7) 12.0
## 575 11 4 1.56 1 Week 1 (study day 1 to 7) 12.0
## 576 11 5 25.9 1 Week 1 (study day 1 to 7) 12.0
## 577 11 6 26.0 1 Week 1 (study day 1 to 7) 12.0
## 578 11 7 3.12 1 Week 1 (study day 1 to 7) 12.0
## 579 11 8 3.12 2 Week 2 (study day 8 to 14) 3.21
## 580 11 9 3.22 2 Week 2 (study day 8 to 14) 3.21
## 581 11 10 3.22 2 Week 2 (study day 8 to 14) 3.21
## 582 11 11 3.22 2 Week 2 (study day 8 to 14) 3.21
## 583 11 12 3.22 2 Week 2 (study day 8 to 14) 3.21
## 584 11 13 3.22 2 Week 2 (study day 8 to 14) 3.21
## 585 11 14 3.22 2 Week 2 (study day 8 to 14) 3.21
## 586 11 15 3.14 3 Week 3 (study day 15 to 21) 2.91
## 587 11 16 3.14 3 Week 3 (study day 15 to 21) 2.91
## 588 11 17 3.14 3 Week 3 (study day 15 to 21) 2.91
## 589 11 18 3.14 3 Week 3 (study day 15 to 21) 2.91
## 590 11 19 3.14 3 Week 3 (study day 15 to 21) 2.91
## 591 11 20 2.35 3 Week 3 (study day 15 to 21) 2.91
## 592 11 21 2.35 3 Week 3 (study day 15 to 21) 2.91
## 593 11 22 2.35 4 Week 4 (study day 22 to 28) 1.52
## 594 11 23 1.57 4 Week 4 (study day 22 to 28) 1.52
## 595 11 24 1.57 4 Week 4 (study day 22 to 28) 1.52
## 596 11 25 1.52 4 Week 4 (study day 22 to 28) 1.52
## 597 11 26 1.21 4 Week 4 (study day 22 to 28) 1.52
## 598 11 27 1.21 4 Week 4 (study day 22 to 28) 1.52
## 599 11 28 1.20 4 Week 4 (study day 22 to 28) 1.52
## 600 11 29 1.20 5 Week 5 (study day 29 to 35) 0.985
## 601 11 30 0.996 5 Week 5 (study day 29 to 35) 0.985
## 602 11 31 0.996 5 Week 5 (study day 29 to 35) 0.985
## 603 11 32 0.977 5 Week 5 (study day 29 to 35) 0.985
## 604 11 33 0.977 5 Week 5 (study day 29 to 35) 0.985
## 605 11 34 0.977 5 Week 5 (study day 29 to 35) 0.985
## 606 11 35 0.781 5 Week 5 (study day 29 to 35) 0.985
## 607 11 36 0.781 6 Week 6 (study day 36 to 42) 0.736
## 608 11 37 0.781 6 Week 6 (study day 36 to 42) 0.736
## 609 11 38 0.756 6 Week 6 (study day 36 to 42) 0.736
## 610 11 39 0.756 6 Week 6 (study day 36 to 42) 0.736
## 611 11 40 0.756 6 Week 6 (study day 36 to 42) 0.736
## 612 11 41 0.756 6 Week 6 (study day 36 to 42) 0.736
## 613 11 42 0.567 6 Week 6 (study day 36 to 42) 0.736
## 614 11 43 0.567 7 Week 7 (study day 43 to 49) 0.557
## 615 11 44 0.567 7 Week 7 (study day 43 to 49) 0.557
## 616 11 45 0.554 7 Week 7 (study day 43 to 49) 0.557
## 617 11 46 0.554 7 Week 7 (study day 43 to 49) 0.557
## 618 11 47 0.554 7 Week 7 (study day 43 to 49) 0.557
## 619 11 48 0.554 7 Week 7 (study day 43 to 49) 0.557
## 620 11 49 0.554 7 Week 7 (study day 43 to 49) 0.557
## 621 11 50 0.554 8 Week 8 (study day 50 to 56) 0.511
## 622 11 51 0.545 8 Week 8 (study day 50 to 56) 0.511
## 623 11 52 0.545 8 Week 8 (study day 50 to 56) 0.511
## 624 11 53 0.545 8 Week 8 (study day 50 to 56) 0.511
## 625 11 54 0.364 8 Week 8 (study day 50 to 56) 0.511
## 626 12 0 35.4 0 Baseline 35.4
## 627 12 1 37.5 1 Week 1 (study day 1 to 7) 16.5
## 628 12 2 37.5 1 Week 1 (study day 1 to 7) 16.5
## 629 12 3 20.3 1 Week 1 (study day 1 to 7) 16.5
## 630 12 4 4.05 1 Week 1 (study day 1 to 7) 16.5
## 631 12 5 5.41 1 Week 1 (study day 1 to 7) 16.5
## 632 12 6 5.36 1 Week 1 (study day 1 to 7) 16.5
## 633 12 7 5.36 1 Week 1 (study day 1 to 7) 16.5
## 634 12 8 2.68 2 Week 2 (study day 8 to 14) 2.26
## 635 12 9 2.52 2 Week 2 (study day 8 to 14) 2.26
## 636 12 10 2.52 2 Week 2 (study day 8 to 14) 2.26
## 637 12 11 2.52 2 Week 2 (study day 8 to 14) 2.26
## 638 12 12 2.54 2 Week 2 (study day 8 to 14) 2.26
## 639 12 13 1.27 2 Week 2 (study day 8 to 14) 2.26
## 640 12 14 1.78 2 Week 2 (study day 8 to 14) 2.26
## 641 12 15 1.68 3 Week 3 (study day 15 to 21) 1.39
## 642 12 16 1.44 3 Week 3 (study day 15 to 21) 1.39
## 643 12 17 1.44 3 Week 3 (study day 15 to 21) 1.39
## 644 12 18 1.44 3 Week 3 (study day 15 to 21) 1.39
## 645 12 19 1.40 3 Week 3 (study day 15 to 21) 1.39
## 646 12 20 1.16 3 Week 3 (study day 15 to 21) 1.39
## 647 12 21 1.16 3 Week 3 (study day 15 to 21) 1.39
## 648 12 22 1.19 4 Week 4 (study day 22 to 28) 1.12
## 649 12 23 1.90 4 Week 4 (study day 22 to 28) 1.12
## 650 12 24 0.952 4 Week 4 (study day 22 to 28) 1.12
## 651 12 25 0.945 4 Week 4 (study day 22 to 28) 1.12
## 652 12 26 0.945 4 Week 4 (study day 22 to 28) 1.12
## 653 12 27 0.945 4 Week 4 (study day 22 to 28) 1.12
## 654 12 28 0.976 4 Week 4 (study day 22 to 28) 1.12
## 655 12 29 0.976 5 Week 5 (study day 29 to 35) 0.976
## 656 12 30 0.976 5 Week 5 (study day 29 to 35) 0.976
## 657 12 31 0.976 5 Week 5 (study day 29 to 35) 0.976
## 658 12 32 0.976 5 Week 5 (study day 29 to 35) 0.976
## 659 12 33 0.976 5 Week 5 (study day 29 to 35) 0.976
## 660 12 34 0.976 5 Week 5 (study day 29 to 35) 0.976
## 661 12 35 0.976 5 Week 5 (study day 29 to 35) 0.976
## 662 12 36 0.96 6 Week 6 (study day 36 to 42) 0.96
## 663 12 37 0.96 6 Week 6 (study day 36 to 42) 0.96
## 664 12 38 0.96 6 Week 6 (study day 36 to 42) 0.96
## 665 12 39 0.96 6 Week 6 (study day 36 to 42) 0.96
## 666 12 40 0.96 6 Week 6 (study day 36 to 42) 0.96
## 667 12 41 0.96 6 Week 6 (study day 36 to 42) 0.96
## 668 12 42 0.96 6 Week 6 (study day 36 to 42) 0.96
## 669 12 43 0.96 7 Week 7 (study day 43 to 49) 0.96
## 670 12 44 0.96 7 Week 7 (study day 43 to 49) 0.96
## 671 12 45 0.96 7 Week 7 (study day 43 to 49) 0.96
## 672 12 46 0.96 7 Week 7 (study day 43 to 49) 0.96
## 673 12 47 0.96 7 Week 7 (study day 43 to 49) 0.96
## 674 12 48 0.96 7 Week 7 (study day 43 to 49) 0.96
## 675 12 49 0.96 7 Week 7 (study day 43 to 49) 0.96
## 676 12 50 0.96 8 Week 8 (study day 50 to 56) 0.96
## 677 12 51 0.96 8 Week 8 (study day 50 to 56) 0.96
## 678 12 52 0.96 8 Week 8 (study day 50 to 56) 0.96
## 679 12 53 0.96 8 Week 8 (study day 50 to 56) 0.96
## 680 12 54 0.96 8 Week 8 (study day 50 to 56) 0.96
## 681 12 55 0.96 8 Week 8 (study day 50 to 56) 0.96
## 682 12 56 0.96 8 Week 8 (study day 50 to 56) 0.96
## 683 13 0 2.23 0 Baseline 2.23
## 684 13 1 2.27 1 Week 1 (study day 1 to 7) 2.32
## 685 13 2 2.27 1 Week 1 (study day 1 to 7) 2.32
## 686 13 3 2.30 1 Week 1 (study day 1 to 7) 2.32
## 687 13 4 2.30 1 Week 1 (study day 1 to 7) 2.32
## 688 13 5 2.30 1 Week 1 (study day 1 to 7) 2.32
## 689 13 6 2.39 1 Week 1 (study day 1 to 7) 2.32
## 690 13 7 2.39 1 Week 1 (study day 1 to 7) 2.32
## 691 13 8 2.39 2 Week 2 (study day 8 to 14) 2.37
## 692 13 9 2.38 2 Week 2 (study day 8 to 14) 2.37
## 693 13 10 2.38 2 Week 2 (study day 8 to 14) 2.37
## 694 13 11 2.38 2 Week 2 (study day 8 to 14) 2.37
## 695 13 12 2.35 2 Week 2 (study day 8 to 14) 2.37
## 696 13 13 2.35 2 Week 2 (study day 8 to 14) 2.37
## 697 13 14 2.35 2 Week 2 (study day 8 to 14) 2.37
## 698 13 15 2.37 3 Week 3 (study day 15 to 21) 2.25
## 699 13 16 4.27 3 Week 3 (study day 15 to 21) 2.25
## 700 13 17 1.90 3 Week 3 (study day 15 to 21) 2.25
## 701 13 18 1.81 3 Week 3 (study day 15 to 21) 2.25
## 702 13 19 1.81 3 Week 3 (study day 15 to 21) 2.25
## 703 13 20 1.81 3 Week 3 (study day 15 to 21) 2.25
## 704 13 21 1.78 3 Week 3 (study day 15 to 21) 2.25
## 705 13 22 1.78 4 Week 4 (study day 22 to 28) 1.41
## 706 13 23 1.67 4 Week 4 (study day 22 to 28) 1.41
## 707 13 24 1.65 4 Week 4 (study day 22 to 28) 1.41
## 708 13 25 1.54 4 Week 4 (study day 22 to 28) 1.41
## 709 13 26 1.10 4 Week 4 (study day 22 to 28) 1.41
## 710 13 27 1.10 4 Week 4 (study day 22 to 28) 1.41
## 711 13 28 1.05 4 Week 4 (study day 22 to 28) 1.41
## 712 13 29 1.05 5 Week 5 (study day 29 to 35) 1.03
## 713 13 30 1.05 5 Week 5 (study day 29 to 35) 1.03
## 714 13 31 1.05 5 Week 5 (study day 29 to 35) 1.03
## 715 13 32 1.05 5 Week 5 (study day 29 to 35) 1.03
## 716 13 33 1.05 5 Week 5 (study day 29 to 35) 1.03
## 717 13 34 0.990 5 Week 5 (study day 29 to 35) 1.03
## 718 13 35 0.990 5 Week 5 (study day 29 to 35) 1.03
## 719 13 36 0.990 6 Week 6 (study day 36 to 42) 0.983
## 720 13 37 0.990 6 Week 6 (study day 36 to 42) 0.983
## 721 13 38 0.990 6 Week 6 (study day 36 to 42) 0.983
## 722 13 39 0.990 6 Week 6 (study day 36 to 42) 0.983
## 723 13 40 0.990 6 Week 6 (study day 36 to 42) 0.983
## 724 13 41 0.965 6 Week 6 (study day 36 to 42) 0.983
## 725 13 42 0.965 6 Week 6 (study day 36 to 42) 0.983
## 726 13 43 0.772 7 Week 7 (study day 43 to 49) 0.775
## 727 13 44 0.772 7 Week 7 (study day 43 to 49) 0.775
## 728 13 45 0.772 7 Week 7 (study day 43 to 49) 0.775
## 729 13 46 0.772 7 Week 7 (study day 43 to 49) 0.775
## 730 13 47 0.772 7 Week 7 (study day 43 to 49) 0.775
## 731 13 48 0.781 7 Week 7 (study day 43 to 49) 0.775
## 732 13 49 0.781 7 Week 7 (study day 43 to 49) 0.775
## 733 13 50 0.781 8 Week 8 (study day 50 to 56) 0.606
## 734 13 51 0.586 8 Week 8 (study day 50 to 56) 0.606
## 735 13 52 0.586 8 Week 8 (study day 50 to 56) 0.606
## 736 13 53 0.586 8 Week 8 (study day 50 to 56) 0.606
## 737 13 54 0.586 8 Week 8 (study day 50 to 56) 0.606
## 738 13 55 0.559 8 Week 8 (study day 50 to 56) 0.606
## 739 13 56 0.559 8 Week 8 (study day 50 to 56) 0.606
## 740 14 0 2.48 0 Baseline 2.48
## 741 14 1 4.90 1 Week 1 (study day 1 to 7) 5.00
## 742 14 2 4.90 1 Week 1 (study day 1 to 7) 5.00
## 743 14 3 5.04 1 Week 1 (study day 1 to 7) 5.00
## 744 14 4 5.04 1 Week 1 (study day 1 to 7) 5.00
## 745 14 5 5.04 1 Week 1 (study day 1 to 7) 5.00
## 746 14 6 5.09 1 Week 1 (study day 1 to 7) 5.00
## 747 14 7 5 1 Week 1 (study day 1 to 7) 5.00
## 748 14 8 5 2 Week 2 (study day 8 to 14) 4.19
## 749 14 9 4.86 2 Week 2 (study day 8 to 14) 4.19
## 750 14 10 4.86 2 Week 2 (study day 8 to 14) 4.19
## 751 14 11 4.75 2 Week 2 (study day 8 to 14) 4.19
## 752 14 12 2.85 2 Week 2 (study day 8 to 14) 4.19
## 753 14 13 3.91 2 Week 2 (study day 8 to 14) 4.19
## 754 14 14 3.10 2 Week 2 (study day 8 to 14) 4.19
## 755 14 15 3.20 3 Week 3 (study day 15 to 21) 2.67
## 756 14 16 2.82 3 Week 3 (study day 15 to 21) 2.67
## 757 14 17 2.82 3 Week 3 (study day 15 to 21) 2.67
## 758 14 18 2.98 3 Week 3 (study day 15 to 21) 2.67
## 759 14 19 2.58 3 Week 3 (study day 15 to 21) 2.67
## 760 14 20 2.29 3 Week 3 (study day 15 to 21) 2.67
## 761 14 21 2 3 Week 3 (study day 15 to 21) 2.67
## 762 14 22 1.63 4 Week 4 (study day 22 to 28) 1.38
## 763 14 23 1.48 4 Week 4 (study day 22 to 28) 1.38
## 764 14 24 1.48 4 Week 4 (study day 22 to 28) 1.38
## 765 14 25 1.28 4 Week 4 (study day 22 to 28) 1.38
## 766 14 26 1.28 4 Week 4 (study day 22 to 28) 1.38
## 767 14 27 1.28 4 Week 4 (study day 22 to 28) 1.38
## 768 14 28 1.28 4 Week 4 (study day 22 to 28) 1.38
## 769 14 29 1.26 5 Week 5 (study day 29 to 35) 1.27
## 770 14 30 1.26 5 Week 5 (study day 29 to 35) 1.27
## 771 14 31 1.26 5 Week 5 (study day 29 to 35) 1.27
## 772 14 32 1.26 5 Week 5 (study day 29 to 35) 1.27
## 773 14 33 1.26 5 Week 5 (study day 29 to 35) 1.27
## 774 14 34 1.30 5 Week 5 (study day 29 to 35) 1.27
## 775 14 35 1.30 5 Week 5 (study day 29 to 35) 1.27
## 776 14 36 1.30 6 Week 6 (study day 36 to 42) 1.29
## 777 14 37 1.30 6 Week 6 (study day 36 to 42) 1.29
## 778 14 38 1.30 6 Week 6 (study day 36 to 42) 1.29
## 779 14 39 1.30 6 Week 6 (study day 36 to 42) 1.29
## 780 14 40 1.30 6 Week 6 (study day 36 to 42) 1.29
## 781 14 41 1.27 6 Week 6 (study day 36 to 42) 1.29
## 782 14 42 1.27 6 Week 6 (study day 36 to 42) 1.29
## 783 14 43 1.27 7 Week 7 (study day 43 to 49) 1.27
## 784 14 44 1.27 7 Week 7 (study day 43 to 49) 1.27
## 785 14 45 1.27 7 Week 7 (study day 43 to 49) 1.27
## 786 14 46 1.27 7 Week 7 (study day 43 to 49) 1.27
## 787 14 47 1.27 7 Week 7 (study day 43 to 49) 1.27
## 788 14 48 1.27 7 Week 7 (study day 43 to 49) 1.27
## 789 14 49 1.27 7 Week 7 (study day 43 to 49) 1.27
## 790 14 50 1.27 8 Week 8 (study day 50 to 56) 1.34
## 791 14 51 1.27 8 Week 8 (study day 50 to 56) 1.34
## 792 14 52 1.36 8 Week 8 (study day 50 to 56) 1.34
## 793 14 53 1.36 8 Week 8 (study day 50 to 56) 1.34
## 794 14 54 1.36 8 Week 8 (study day 50 to 56) 1.34
## 795 14 55 1.36 8 Week 8 (study day 50 to 56) 1.34
## 796 14 56 1.36 8 Week 8 (study day 50 to 56) 1.34
## 797 15 0 5.29 0 Baseline 5.29
## 798 15 1 5.39 1 Week 1 (study day 1 to 7) 4.02
## 799 15 2 5.39 1 Week 1 (study day 1 to 7) 4.02
## 800 15 3 5.39 1 Week 1 (study day 1 to 7) 4.02
## 801 15 4 4.05 1 Week 1 (study day 1 to 7) 4.02
## 802 15 5 2.70 1 Week 1 (study day 1 to 7) 4.02
## 803 15 6 2.59 1 Week 1 (study day 1 to 7) 4.02
## 804 15 7 2.59 1 Week 1 (study day 1 to 7) 4.02
## 805 15 8 2.59 2 Week 2 (study day 8 to 14) 2.47
## 806 15 9 2.59 2 Week 2 (study day 8 to 14) 2.47
## 807 15 10 2.59 2 Week 2 (study day 8 to 14) 2.47
## 808 15 11 2.59 2 Week 2 (study day 8 to 14) 2.47
## 809 15 12 2.33 2 Week 2 (study day 8 to 14) 2.47
## 810 15 13 2.28 2 Week 2 (study day 8 to 14) 2.47
## 811 15 14 2.28 2 Week 2 (study day 8 to 14) 2.47
## 812 15 15 2.28 3 Week 3 (study day 15 to 21) 2.32
## 813 15 16 2.32 3 Week 3 (study day 15 to 21) 2.32
## 814 15 17 2.32 3 Week 3 (study day 15 to 21) 2.32
## 815 15 18 2.32 3 Week 3 (study day 15 to 21) 2.32
## 816 15 19 2.32 3 Week 3 (study day 15 to 21) 2.32
## 817 15 20 2.34 3 Week 3 (study day 15 to 21) 2.32
## 818 15 21 2.34 3 Week 3 (study day 15 to 21) 2.32
## 819 15 22 2.34 4 Week 4 (study day 22 to 28) 2.13
## 820 15 23 2.26 4 Week 4 (study day 22 to 28) 2.13
## 821 15 24 2.26 4 Week 4 (study day 22 to 28) 2.13
## 822 15 25 2.01 4 Week 4 (study day 22 to 28) 2.13
## 823 15 26 2.01 4 Week 4 (study day 22 to 28) 2.13
## 824 15 27 2.01 4 Week 4 (study day 22 to 28) 2.13
## 825 15 28 2.01 4 Week 4 (study day 22 to 28) 2.13
## 826 15 29 2.01 5 Week 5 (study day 29 to 35) 1.96
## 827 15 30 1.96 5 Week 5 (study day 29 to 35) 1.96
## 828 15 31 1.96 5 Week 5 (study day 29 to 35) 1.96
## 829 15 32 1.96 5 Week 5 (study day 29 to 35) 1.96
## 830 15 33 1.96 5 Week 5 (study day 29 to 35) 1.96
## 831 15 34 1.96 5 Week 5 (study day 29 to 35) 1.96
## 832 15 35 1.93 5 Week 5 (study day 29 to 35) 1.96
## 833 15 36 1.93 6 Week 6 (study day 36 to 42) 1.75
## 834 15 37 1.93 6 Week 6 (study day 36 to 42) 1.75
## 835 15 38 1.69 6 Week 6 (study day 36 to 42) 1.75
## 836 15 39 1.69 6 Week 6 (study day 36 to 42) 1.75
## 837 15 40 1.69 6 Week 6 (study day 36 to 42) 1.75
## 838 15 41 1.67 6 Week 6 (study day 36 to 42) 1.75
## 839 15 42 1.67 6 Week 6 (study day 36 to 42) 1.75
## 840 15 43 1.67 7 Week 7 (study day 43 to 49) 1.66
## 841 15 44 1.67 7 Week 7 (study day 43 to 49) 1.66
## 842 15 45 1.67 7 Week 7 (study day 43 to 49) 1.66
## 843 15 46 1.67 7 Week 7 (study day 43 to 49) 1.66
## 844 15 47 1.67 7 Week 7 (study day 43 to 49) 1.66
## 845 15 48 1.62 7 Week 7 (study day 43 to 49) 1.66
## 846 15 49 1.62 7 Week 7 (study day 43 to 49) 1.66
## 847 15 50 1.62 8 Week 8 (study day 50 to 56) 1.62
## 848 15 51 1.62 8 Week 8 (study day 50 to 56) 1.62
## 849 15 52 1.62 8 Week 8 (study day 50 to 56) 1.62
## 850 15 53 1.62 8 Week 8 (study day 50 to 56) 1.62
## 851 15 54 1.62 8 Week 8 (study day 50 to 56) 1.62
## 852 15 55 1.64 8 Week 8 (study day 50 to 56) 1.62
## 853 15 56 1.64 8 Week 8 (study day 50 to 56) 1.62
## 854 16 0 36.8 0 Baseline 36.8
## 855 16 1 3.73 1 Week 1 (study day 1 to 7) 3.53
## 856 16 2 3.73 1 Week 1 (study day 1 to 7) 3.53
## 857 16 3 2.94 1 Week 1 (study day 1 to 7) 3.53
## 858 16 4 2.94 1 Week 1 (study day 1 to 7) 3.53
## 859 16 5 2.94 1 Week 1 (study day 1 to 7) 3.53
## 860 16 6 3.01 1 Week 1 (study day 1 to 7) 3.53
## 861 16 7 5.42 1 Week 1 (study day 1 to 7) 3.53
## 862 16 8 2.41 2 Week 2 (study day 8 to 14) 2.38
## 863 16 9 2.4 2 Week 2 (study day 8 to 14) 2.38
## 864 16 10 2.4 2 Week 2 (study day 8 to 14) 2.38
## 865 16 11 2.4 2 Week 2 (study day 8 to 14) 2.38
## 866 16 12 2.4 2 Week 2 (study day 8 to 14) 2.38
## 867 16 13 2.33 2 Week 2 (study day 8 to 14) 2.38
## 868 16 14 2.33 2 Week 2 (study day 8 to 14) 2.38
## 869 16 15 1.75 3 Week 3 (study day 15 to 21) 1.72
## 870 16 16 1.71 3 Week 3 (study day 15 to 21) 1.72
## 871 16 17 1.71 3 Week 3 (study day 15 to 21) 1.72
## 872 16 18 1.71 3 Week 3 (study day 15 to 21) 1.72
## 873 16 19 1.71 3 Week 3 (study day 15 to 21) 1.72
## 874 16 20 1.73 3 Week 3 (study day 15 to 21) 1.72
## 875 16 21 1.73 3 Week 3 (study day 15 to 21) 1.72
## 876 16 22 1.15 4 Week 4 (study day 22 to 28) 1.16
## 877 16 23 1.17 4 Week 4 (study day 22 to 28) 1.16
## 878 16 24 1.17 4 Week 4 (study day 22 to 28) 1.16
## 879 16 25 1.17 4 Week 4 (study day 22 to 28) 1.16
## 880 16 26 1.17 4 Week 4 (study day 22 to 28) 1.16
## 881 16 27 1.14 4 Week 4 (study day 22 to 28) 1.16
## 882 16 28 1.14 4 Week 4 (study day 22 to 28) 1.16
## 883 16 29 0.857 5 Week 5 (study day 29 to 35) 0.881
## 884 16 30 0.857 5 Week 5 (study day 29 to 35) 0.881
## 885 16 31 0.882 5 Week 5 (study day 29 to 35) 0.881
## 886 16 32 0.882 5 Week 5 (study day 29 to 35) 0.881
## 887 16 33 0.882 5 Week 5 (study day 29 to 35) 0.881
## 888 16 34 0.882 5 Week 5 (study day 29 to 35) 0.881
## 889 16 35 0.920 5 Week 5 (study day 29 to 35) 0.881
## 890 16 36 0.920 6 Week 6 (study day 36 to 42) 0.644
## 891 16 37 0.613 6 Week 6 (study day 36 to 42) 0.644
## 892 16 38 0.613 6 Week 6 (study day 36 to 42) 0.644
## 893 16 39 0.613 6 Week 6 (study day 36 to 42) 0.644
## 894 16 40 0.583 6 Week 6 (study day 36 to 42) 0.644
## 895 16 41 0.583 6 Week 6 (study day 36 to 42) 0.644
## 896 16 42 0.583 6 Week 6 (study day 36 to 42) 0.644
## 897 16 43 0.583 7 Week 7 (study day 43 to 49) 0.590
## 898 16 44 0.583 7 Week 7 (study day 43 to 49) 0.590
## 899 16 45 0.583 7 Week 7 (study day 43 to 49) 0.590
## 900 16 46 0.583 7 Week 7 (study day 43 to 49) 0.590
## 901 16 47 0.583 7 Week 7 (study day 43 to 49) 0.590
## 902 16 48 0.609 7 Week 7 (study day 43 to 49) 0.590
## 903 16 49 0.609 7 Week 7 (study day 43 to 49) 0.590
## 904 16 50 0.609 8 Week 8 (study day 50 to 56) 0.506
## 905 16 51 0.487 8 Week 8 (study day 50 to 56) 0.506
## 906 16 52 0.487 8 Week 8 (study day 50 to 56) 0.506
## 907 16 53 0.487 8 Week 8 (study day 50 to 56) 0.506
## 908 16 54 0.487 8 Week 8 (study day 50 to 56) 0.506
## 909 16 55 0.492 8 Week 8 (study day 50 to 56) 0.506
## 910 16 56 0.492 8 Week 8 (study day 50 to 56) 0.506
## 911 17 0 0.990 0 Baseline 0.990
## 912 17 1 0.990 1 Week 1 (study day 1 to 7) 0.997
## 913 17 2 0.990 1 Week 1 (study day 1 to 7) 0.997
## 914 17 3 0.995 1 Week 1 (study day 1 to 7) 0.997
## 915 17 4 0.995 1 Week 1 (study day 1 to 7) 0.997
## 916 17 5 0.995 1 Week 1 (study day 1 to 7) 0.997
## 917 17 6 1.01 1 Week 1 (study day 1 to 7) 0.997
## 918 17 7 1.01 1 Week 1 (study day 1 to 7) 0.997
## 919 17 8 1.01 2 Week 2 (study day 8 to 14) 0.666
## 920 17 9 0.694 2 Week 2 (study day 8 to 14) 0.666
## 921 17 10 0.694 2 Week 2 (study day 8 to 14) 0.666
## 922 17 11 0.694 2 Week 2 (study day 8 to 14) 0.666
## 923 17 12 0.525 2 Week 2 (study day 8 to 14) 0.666
## 924 17 13 0.525 2 Week 2 (study day 8 to 14) 0.666
## 925 17 14 0.525 2 Week 2 (study day 8 to 14) 0.666
## 926 17 15 0.522 3 Week 3 (study day 15 to 21) 0.518
## 927 17 16 0.522 3 Week 3 (study day 15 to 21) 0.518
## 928 17 17 0.522 3 Week 3 (study day 15 to 21) 0.518
## 929 17 18 0.522 3 Week 3 (study day 15 to 21) 0.518
## 930 17 19 0.513 3 Week 3 (study day 15 to 21) 0.518
## 931 17 20 0.513 3 Week 3 (study day 15 to 21) 0.518
## 932 17 21 0.513 3 Week 3 (study day 15 to 21) 0.518
## 933 17 22 0.513 4 Week 4 (study day 22 to 28) 0.504
## 934 17 23 0.504 4 Week 4 (study day 22 to 28) 0.504
## 935 17 24 0.504 4 Week 4 (study day 22 to 28) 0.504
## 936 17 25 0.504 4 Week 4 (study day 22 to 28) 0.504
## 937 17 26 0.501 4 Week 4 (study day 22 to 28) 0.504
## 938 17 27 0.501 4 Week 4 (study day 22 to 28) 0.504
## 939 17 28 0.501 4 Week 4 (study day 22 to 28) 0.504
## 940 17 29 0.501 5 Week 5 (study day 29 to 35) 0.492
## 941 17 30 0.501 5 Week 5 (study day 29 to 35) 0.492
## 942 17 31 0.501 5 Week 5 (study day 29 to 35) 0.492
## 943 17 32 0.501 5 Week 5 (study day 29 to 35) 0.492
## 944 17 33 0.48 5 Week 5 (study day 29 to 35) 0.492
## 945 17 34 0.48 5 Week 5 (study day 29 to 35) 0.492
## 946 17 35 0.48 5 Week 5 (study day 29 to 35) 0.492
## 947 17 36 0.48 6 Week 6 (study day 36 to 42) 0.48
## 948 17 37 0.48 6 Week 6 (study day 36 to 42) 0.48
## 949 17 38 0.48 6 Week 6 (study day 36 to 42) 0.48
## 950 17 39 0.48 6 Week 6 (study day 36 to 42) 0.48
## 951 17 40 0.48 6 Week 6 (study day 36 to 42) 0.48
## 952 17 41 0.48 6 Week 6 (study day 36 to 42) 0.48
## 953 17 42 0.48 6 Week 6 (study day 36 to 42) 0.48
## 954 17 43 0.48 7 Week 7 (study day 43 to 49) 0.459
## 955 17 44 0.48 7 Week 7 (study day 43 to 49) 0.459
## 956 17 45 0.48 7 Week 7 (study day 43 to 49) 0.459
## 957 17 46 0.484 7 Week 7 (study day 43 to 49) 0.459
## 958 17 47 0.484 7 Week 7 (study day 43 to 49) 0.459
## 959 17 48 0.403 7 Week 7 (study day 43 to 49) 0.459
## 960 17 49 0.403 7 Week 7 (study day 43 to 49) 0.459
## 961 17 50 0.403 8 Week 8 (study day 50 to 56) 0.392
## 962 17 51 0.391 8 Week 8 (study day 50 to 56) 0.392
## 963 17 52 0.391 8 Week 8 (study day 50 to 56) 0.392
## 964 17 53 0.391 8 Week 8 (study day 50 to 56) 0.392
## 965 17 54 0.391 8 Week 8 (study day 50 to 56) 0.392
## 966 17 55 0.391 8 Week 8 (study day 50 to 56) 0.392
## 967 17 56 0.391 8 Week 8 (study day 50 to 56) 0.392
## 968 18 0 4.38 0 Baseline 4.38
## 969 18 1 4.44 1 Week 1 (study day 1 to 7) 4.41
## 970 18 2 4.44 1 Week 1 (study day 1 to 7) 4.41
## 971 18 3 4.47 1 Week 1 (study day 1 to 7) 4.41
## 972 18 4 4.47 1 Week 1 (study day 1 to 7) 4.41
## 973 18 5 4.47 1 Week 1 (study day 1 to 7) 4.41
## 974 18 6 4.29 1 Week 1 (study day 1 to 7) 4.41
## 975 18 7 4.29 1 Week 1 (study day 1 to 7) 4.41
## 976 18 8 4.29 2 Week 2 (study day 8 to 14) 4.10
## 977 18 9 4.48 2 Week 2 (study day 8 to 14) 4.10
## 978 18 10 4.48 2 Week 2 (study day 8 to 14) 4.10
## 979 18 11 4.48 2 Week 2 (study day 8 to 14) 4.10
## 980 18 12 4.47 2 Week 2 (study day 8 to 14) 4.10
## 981 18 13 4.47 2 Week 2 (study day 8 to 14) 4.10
## 982 18 14 2.02 2 Week 2 (study day 8 to 14) 4.10
## 983 18 15 1.98 3 Week 3 (study day 15 to 21) 3.87
## 984 18 16 4.17 3 Week 3 (study day 15 to 21) 3.87
## 985 18 17 4.17 3 Week 3 (study day 15 to 21) 3.87
## 986 18 18 4.21 3 Week 3 (study day 15 to 21) 3.87
## 987 18 19 4.21 3 Week 3 (study day 15 to 21) 3.87
## 988 18 20 4.21 3 Week 3 (study day 15 to 21) 3.87
## 989 18 21 4.12 3 Week 3 (study day 15 to 21) 3.87
## 990 18 22 4.12 4 Week 4 (study day 22 to 28) 4.11
## 991 18 23 4.12 4 Week 4 (study day 22 to 28) 4.11
## 992 18 24 4.11 4 Week 4 (study day 22 to 28) 4.11
## 993 18 25 4.11 4 Week 4 (study day 22 to 28) 4.11
## 994 18 26 4.11 4 Week 4 (study day 22 to 28) 4.11
## 995 18 27 4.09 4 Week 4 (study day 22 to 28) 4.11
## 996 18 28 4.09 4 Week 4 (study day 22 to 28) 4.11
## 997 18 29 4.09 5 Week 5 (study day 29 to 35) 4.13
## 998 18 30 4.14 5 Week 5 (study day 29 to 35) 4.13
## 999 18 31 4.14 5 Week 5 (study day 29 to 35) 4.13
## 1000 18 32 4.14 5 Week 5 (study day 29 to 35) 4.13
## 1001 18 33 4.14 5 Week 5 (study day 29 to 35) 4.13
## 1002 18 34 4.14 5 Week 5 (study day 29 to 35) 4.13
## 1003 18 35 4.14 5 Week 5 (study day 29 to 35) 4.13
## 1004 18 36 4.14 6 Week 6 (study day 36 to 42) 3.15
## 1005 18 37 4.01 6 Week 6 (study day 36 to 42) 3.15
## 1006 18 38 4.01 6 Week 6 (study day 36 to 42) 3.15
## 1007 18 39 2.51 6 Week 6 (study day 36 to 42) 3.15
## 1008 18 40 2.51 6 Week 6 (study day 36 to 42) 3.15
## 1009 18 41 2.5 6 Week 6 (study day 36 to 42) 3.15
## 1010 18 42 2.35 6 Week 6 (study day 36 to 42) 3.15
## 1011 18 43 2.35 7 Week 7 (study day 43 to 49) 2.34
## 1012 18 44 2.36 7 Week 7 (study day 43 to 49) 2.34
## 1013 18 45 2.36 7 Week 7 (study day 43 to 49) 2.34
## 1014 18 46 2.36 7 Week 7 (study day 43 to 49) 2.34
## 1015 18 47 2.36 7 Week 7 (study day 43 to 49) 2.34
## 1016 18 48 2.31 7 Week 7 (study day 43 to 49) 2.34
## 1017 18 49 2.31 7 Week 7 (study day 43 to 49) 2.34
## 1018 18 50 1.87 8 Week 8 (study day 50 to 56) 1.86
## 1019 18 51 1.86 8 Week 8 (study day 50 to 56) 1.86
## 1020 18 52 1.86 8 Week 8 (study day 50 to 56) 1.86
## 1021 18 53 1.86 8 Week 8 (study day 50 to 56) 1.86
## 1022 18 54 1.86 8 Week 8 (study day 50 to 56) 1.86
## 1023 18 55 1.86 8 Week 8 (study day 50 to 56) 1.86
## 1024 18 56 1.86 8 Week 8 (study day 50 to 56) 1.86
## 1025 19 0 0.727 0 Baseline 0.727
## 1026 19 1 0.727 1 Week 1 (study day 1 to 7) 0.727
## 1027 19 2 0.727 1 Week 1 (study day 1 to 7) 0.727
## 1028 19 3 0.727 1 Week 1 (study day 1 to 7) 0.727
## 1029 19 4 0.727 1 Week 1 (study day 1 to 7) 0.727
## 1030 19 5 0.727 1 Week 1 (study day 1 to 7) 0.727
## 1031 19 6 0.727 1 Week 1 (study day 1 to 7) 0.727
## 1032 19 7 0.727 1 Week 1 (study day 1 to 7) 0.727
## 1033 19 8 0.727 2 Week 2 (study day 8 to 14) 0.733
## 1034 19 9 0.741 2 Week 2 (study day 8 to 14) 0.733
## 1035 19 10 0.741 2 Week 2 (study day 8 to 14) 0.733
## 1036 19 11 0.741 2 Week 2 (study day 8 to 14) 0.733
## 1037 19 12 0.727 2 Week 2 (study day 8 to 14) 0.733
## 1038 19 13 0.727 2 Week 2 (study day 8 to 14) 0.733
## 1039 19 14 0.727 2 Week 2 (study day 8 to 14) 0.733
## 1040 19 15 0.727 3 Week 3 (study day 15 to 21) 0.737
## 1041 19 16 0.727 3 Week 3 (study day 15 to 21) 0.737
## 1042 19 17 0.727 3 Week 3 (study day 15 to 21) 0.737
## 1043 19 18 0.741 3 Week 3 (study day 15 to 21) 0.737
## 1044 19 19 0.741 3 Week 3 (study day 15 to 21) 0.737
## 1045 19 20 0.741 3 Week 3 (study day 15 to 21) 0.737
## 1046 19 21 0.755 3 Week 3 (study day 15 to 21) 0.737
## 1047 19 22 0.566 4 Week 4 (study day 22 to 28) 0.556
## 1048 19 23 0.566 4 Week 4 (study day 22 to 28) 0.556
## 1049 19 24 0.566 4 Week 4 (study day 22 to 28) 0.556
## 1050 19 25 0.545 4 Week 4 (study day 22 to 28) 0.556
## 1051 19 26 0.545 4 Week 4 (study day 22 to 28) 0.556
## 1052 19 27 0.545 4 Week 4 (study day 22 to 28) 0.556
## 1053 19 28 0.556 4 Week 4 (study day 22 to 28) 0.556
## 1054 19 29 0.556 5 Week 5 (study day 29 to 35) 0.477
## 1055 19 30 0.463 5 Week 5 (study day 29 to 35) 0.477
## 1056 19 31 0.463 5 Week 5 (study day 29 to 35) 0.477
## 1057 19 32 0.465 5 Week 5 (study day 29 to 35) 0.477
## 1058 19 33 0.465 5 Week 5 (study day 29 to 35) 0.477
## 1059 19 34 0.465 5 Week 5 (study day 29 to 35) 0.477
## 1060 19 35 0.463 5 Week 5 (study day 29 to 35) 0.477
## 1061 19 36 23.6 6 Week 6 (study day 36 to 42) 7.08
## 1062 19 37 12.0 6 Week 6 (study day 36 to 42) 7.08
## 1063 19 38 12.0 6 Week 6 (study day 36 to 42) 7.08
## 1064 19 39 0.463 6 Week 6 (study day 36 to 42) 7.08
## 1065 19 40 0.463 6 Week 6 (study day 36 to 42) 7.08
## 1066 19 41 0.463 6 Week 6 (study day 36 to 42) 7.08
## 1067 19 42 0.459 6 Week 6 (study day 36 to 42) 7.08
## 1068 19 43 0.459 7 Week 7 (study day 43 to 49) 0.536
## 1069 19 44 0.459 7 Week 7 (study day 43 to 49) 0.536
## 1070 19 45 0.550 7 Week 7 (study day 43 to 49) 0.536
## 1071 19 46 0.573 7 Week 7 (study day 43 to 49) 0.536
## 1072 19 47 0.573 7 Week 7 (study day 43 to 49) 0.536
## 1073 19 48 0.573 7 Week 7 (study day 43 to 49) 0.536
## 1074 19 49 0.567 7 Week 7 (study day 43 to 49) 0.536
## 1075 19 50 0.567 8 Week 8 (study day 50 to 56) 0.490
## 1076 19 51 0.473 8 Week 8 (study day 50 to 56) 0.490
## 1077 19 52 0.473 8 Week 8 (study day 50 to 56) 0.490
## 1078 19 53 0.481 8 Week 8 (study day 50 to 56) 0.490
## 1079 19 54 0.481 8 Week 8 (study day 50 to 56) 0.490
## 1080 19 55 0.481 8 Week 8 (study day 50 to 56) 0.490
## 1081 19 56 0.473 8 Week 8 (study day 50 to 56) 0.490
## 1082 20 0 2.67 0 Baseline 2.67
## 1083 20 1 2.67 1 Week 1 (study day 1 to 7) 13.3
## 1084 20 2 3 1 Week 1 (study day 1 to 7) 13.3
## 1085 20 3 3 1 Week 1 (study day 1 to 7) 13.3
## 1086 20 4 2.96 1 Week 1 (study day 1 to 7) 13.3
## 1087 20 5 26.4 1 Week 1 (study day 1 to 7) 13.3
## 1088 20 6 1.01 1 Week 1 (study day 1 to 7) 13.3
## 1089 20 7 1.01 1 Week 1 (study day 1 to 7) 13.3
## 1090 20 8 1.01 2 Week 2 (study day 8 to 14) 11.3
## 1091 20 9 0.968 2 Week 2 (study day 8 to 14) 11.3
## 1092 20 10 25.2 2 Week 2 (study day 8 to 14) 11.3
## 1093 20 11 25.2 2 Week 2 (study day 8 to 14) 11.3
## 1094 20 12 25.2 2 Week 2 (study day 8 to 14) 11.3
## 1095 20 13 0.932 2 Week 2 (study day 8 to 14) 11.3
## 1096 20 14 0.932 2 Week 2 (study day 8 to 14) 11.3
## 1097 20 15 0.932 3 Week 3 (study day 15 to 21) 0.912
## 1098 20 16 0.968 3 Week 3 (study day 15 to 21) 0.912
## 1099 20 17 0.968 3 Week 3 (study day 15 to 21) 0.912
## 1100 20 18 0.968 3 Week 3 (study day 15 to 21) 0.912
## 1101 20 19 0.968 3 Week 3 (study day 15 to 21) 0.912
## 1102 20 20 0.949 3 Week 3 (study day 15 to 21) 0.912
## 1103 20 21 0.633 3 Week 3 (study day 15 to 21) 0.912
## 1104 20 22 0.633 4 Week 4 (study day 22 to 28) 0.604
## 1105 20 23 0.625 4 Week 4 (study day 22 to 28) 0.604
## 1106 20 24 0.625 4 Week 4 (study day 22 to 28) 0.604
## 1107 20 25 0.625 4 Week 4 (study day 22 to 28) 0.604
## 1108 20 26 0.625 4 Week 4 (study day 22 to 28) 0.604
## 1109 20 27 0.625 4 Week 4 (study day 22 to 28) 0.604
## 1110 20 28 0.469 4 Week 4 (study day 22 to 28) 0.604
## 1111 20 29 0.469 5 Week 5 (study day 29 to 35) 0.467
## 1112 20 30 0.469 5 Week 5 (study day 29 to 35) 0.467
## 1113 20 31 0.469 5 Week 5 (study day 29 to 35) 0.467
## 1114 20 32 0.469 5 Week 5 (study day 29 to 35) 0.467
## 1115 20 33 0.469 5 Week 5 (study day 29 to 35) 0.467
## 1116 20 34 0.463 5 Week 5 (study day 29 to 35) 0.467
## 1117 20 35 0.463 5 Week 5 (study day 29 to 35) 0.467
## 1118 20 36 0.386 6 Week 6 (study day 36 to 42) 0.380
## 1119 20 37 0.379 6 Week 6 (study day 36 to 42) 0.380
## 1120 20 38 0.379 6 Week 6 (study day 36 to 42) 0.380
## 1121 20 39 0.379 6 Week 6 (study day 36 to 42) 0.380
## 1122 20 40 0.379 6 Week 6 (study day 36 to 42) 0.380
## 1123 20 41 0.381 6 Week 6 (study day 36 to 42) 0.380
## 1124 20 42 0.381 6 Week 6 (study day 36 to 42) 0.380
## 1125 20 43 0.381 7 Week 7 (study day 43 to 49) 0.379
## 1126 20 44 0.379 7 Week 7 (study day 43 to 49) 0.379
## 1127 20 45 0.379 7 Week 7 (study day 43 to 49) 0.379
## 1128 20 46 0.379 7 Week 7 (study day 43 to 49) 0.379
## 1129 20 47 0.379 7 Week 7 (study day 43 to 49) 0.379
## 1130 20 48 0.379 7 Week 7 (study day 43 to 49) 0.379
## 1131 20 49 0.379 7 Week 7 (study day 43 to 49) 0.379
## 1132 20 50 0.379 8 Week 8 (study day 50 to 56) 0.309
## 1133 20 51 0.299 8 Week 8 (study day 50 to 56) 0.309
## 1134 20 52 0.299 8 Week 8 (study day 50 to 56) 0.309
## 1135 20 53 0.299 8 Week 8 (study day 50 to 56) 0.309
## 1136 20 54 0.299 8 Week 8 (study day 50 to 56) 0.309
## 1137 20 55 0.294 8 Week 8 (study day 50 to 56) 0.309
## 1138 20 56 0.294 8 Week 8 (study day 50 to 56) 0.309
## 1139 21 0 0 0 Baseline 0
## 1140 21 1 24.9 1 Week 1 (study day 1 to 7) 1.28
## 1141 21 2 1.42 1 Week 1 (study day 1 to 7) 1.28
## 1142 21 3 1.39 1 Week 1 (study day 1 to 7) 1.28
## 1143 21 4 1.39 1 Week 1 (study day 1 to 7) 1.28
## 1144 21 5 1.12 1 Week 1 (study day 1 to 7) 1.28
## 1145 21 6 1.11 1 Week 1 (study day 1 to 7) 1.28
## 1146 21 7 1.11 1 Week 1 (study day 1 to 7) 1.28
## 1147 21 8 1.11 2 Week 2 (study day 8 to 14) 2.39
## 1148 21 9 1.09 2 Week 2 (study day 8 to 14) 2.39
## 1149 21 10 11.4 2 Week 2 (study day 8 to 14) 2.39
## 1150 21 11 0.909 2 Week 2 (study day 8 to 14) 2.39
## 1151 21 12 0.759 2 Week 2 (study day 8 to 14) 2.39
## 1152 21 13 0.759 2 Week 2 (study day 8 to 14) 2.39
## 1153 21 14 0.759 2 Week 2 (study day 8 to 14) 2.39
## 1154 21 15 0.750 3 Week 3 (study day 15 to 21) 0.745
## 1155 21 16 0.750 3 Week 3 (study day 15 to 21) 0.745
## 1156 21 17 0.741 3 Week 3 (study day 15 to 21) 0.745
## 1157 21 18 0.741 3 Week 3 (study day 15 to 21) 0.745
## 1158 21 19 0.741 3 Week 3 (study day 15 to 21) 0.745
## 1159 21 20 0.741 3 Week 3 (study day 15 to 21) 0.745
## 1160 21 21 0.752 3 Week 3 (study day 15 to 21) 0.745
## 1161 21 22 0.470 4 Week 4 (study day 22 to 28) 0.466
## 1162 21 23 0.470 4 Week 4 (study day 22 to 28) 0.466
## 1163 21 24 0.465 4 Week 4 (study day 22 to 28) 0.466
## 1164 21 25 0.465 4 Week 4 (study day 22 to 28) 0.466
## 1165 21 26 0.465 4 Week 4 (study day 22 to 28) 0.466
## 1166 21 27 0.465 4 Week 4 (study day 22 to 28) 0.466
## 1167 21 28 0.460 4 Week 4 (study day 22 to 28) 0.466
## 1168 21 29 0.460 5 Week 5 (study day 29 to 35) 0.382
## 1169 21 30 0.368 5 Week 5 (study day 29 to 35) 0.382
## 1170 21 31 0.368 5 Week 5 (study day 29 to 35) 0.382
## 1171 21 32 0.368 5 Week 5 (study day 29 to 35) 0.382
## 1172 21 33 0.370 5 Week 5 (study day 29 to 35) 0.382
## 1173 21 34 0.370 5 Week 5 (study day 29 to 35) 0.382
## 1174 21 35 0.370 5 Week 5 (study day 29 to 35) 0.382
## 1175 21 36 0.370 6 Week 6 (study day 36 to 42) 0.380
## 1176 21 37 0.370 6 Week 6 (study day 36 to 42) 0.380
## 1177 21 38 0.370 6 Week 6 (study day 36 to 42) 0.380
## 1178 21 39 0.370 6 Week 6 (study day 36 to 42) 0.380
## 1179 21 40 0.636 6 Week 6 (study day 36 to 42) 0.380
## 1180 21 41 0.273 6 Week 6 (study day 36 to 42) 0.380
## 1181 21 42 0.273 6 Week 6 (study day 36 to 42) 0.380
## 1182 21 43 0.273 7 Week 7 (study day 43 to 49) 0.274
## 1183 21 44 0.273 7 Week 7 (study day 43 to 49) 0.274
## 1184 21 45 0.273 7 Week 7 (study day 43 to 49) 0.274
## 1185 21 46 0.273 7 Week 7 (study day 43 to 49) 0.274
## 1186 21 47 0.275 7 Week 7 (study day 43 to 49) 0.274
## 1187 21 48 0.275 7 Week 7 (study day 43 to 49) 0.274
## 1188 21 49 0.275 7 Week 7 (study day 43 to 49) 0.274
## 1189 21 50 0.275 8 Week 8 (study day 50 to 56) 0.235
## 1190 21 51 0.275 8 Week 8 (study day 50 to 56) 0.235
## 1191 21 52 0.275 8 Week 8 (study day 50 to 56) 0.235
## 1192 21 53 0.275 8 Week 8 (study day 50 to 56) 0.235
## 1193 21 54 0.181 8 Week 8 (study day 50 to 56) 0.235
## 1194 21 55 0.181 8 Week 8 (study day 50 to 56) 0.235
## 1195 21 56 0.181 8 Week 8 (study day 50 to 56) 0.235
## 1196 22 0 0 0 Baseline 0
## 1197 22 1 0.258 1 Week 1 (study day 1 to 7) 0.258
## 1198 22 2 0.258 1 Week 1 (study day 1 to 7) 0.258
## 1199 22 3 0.258 1 Week 1 (study day 1 to 7) 0.258
## 1200 22 4 0.258 1 Week 1 (study day 1 to 7) 0.258
## 1201 22 5 0.258 1 Week 1 (study day 1 to 7) 0.258
## 1202 22 6 0.257 1 Week 1 (study day 1 to 7) 0.258
## 1203 22 7 0.257 1 Week 1 (study day 1 to 7) 0.258
## 1204 22 8 0.257 2 Week 2 (study day 8 to 14) 0.229
## 1205 22 9 0.257 2 Week 2 (study day 8 to 14) 0.229
## 1206 22 10 0.256 2 Week 2 (study day 8 to 14) 0.229
## 1207 22 11 0.256 2 Week 2 (study day 8 to 14) 0.229
## 1208 22 12 0.192 2 Week 2 (study day 8 to 14) 0.229
## 1209 22 13 0.191 2 Week 2 (study day 8 to 14) 0.229
## 1210 22 14 0.191 2 Week 2 (study day 8 to 14) 0.229
## 1211 22 15 0.191 3 Week 3 (study day 15 to 21) 0.351
## 1212 22 16 0.189 3 Week 3 (study day 15 to 21) 0.351
## 1213 22 17 0.818 3 Week 3 (study day 15 to 21) 0.351
## 1214 22 18 0.314 3 Week 3 (study day 15 to 21) 0.351
## 1215 22 19 0.316 3 Week 3 (study day 15 to 21) 0.351
## 1216 22 20 0.316 3 Week 3 (study day 15 to 21) 0.351
## 1217 22 21 0.314 3 Week 3 (study day 15 to 21) 0.351
## 1218 22 22 0.314 4 Week 4 (study day 22 to 28) 0.240
## 1219 22 23 0.251 4 Week 4 (study day 22 to 28) 0.240
## 1220 22 24 0.251 4 Week 4 (study day 22 to 28) 0.240
## 1221 22 25 0.248 4 Week 4 (study day 22 to 28) 0.240
## 1222 22 26 0.248 4 Week 4 (study day 22 to 28) 0.240
## 1223 22 27 0.186 4 Week 4 (study day 22 to 28) 0.240
## 1224 22 28 0.187 4 Week 4 (study day 22 to 28) 0.240
## 1225 22 29 0.187 5 Week 5 (study day 29 to 35) 0.169
## 1226 22 30 0.187 5 Week 5 (study day 29 to 35) 0.169
## 1227 22 31 0.186 5 Week 5 (study day 29 to 35) 0.169
## 1228 22 32 0.155 5 Week 5 (study day 29 to 35) 0.169
## 1229 22 33 0.155 5 Week 5 (study day 29 to 35) 0.169
## 1230 22 34 0.155 5 Week 5 (study day 29 to 35) 0.169
## 1231 22 35 0.155 5 Week 5 (study day 29 to 35) 0.169
## 1232 22 36 0.124 6 Week 6 (study day 36 to 42) 0.132
## 1233 22 37 0.124 6 Week 6 (study day 36 to 42) 0.132
## 1234 22 38 0.123 6 Week 6 (study day 36 to 42) 0.132
## 1235 22 39 0.123 6 Week 6 (study day 36 to 42) 0.132
## 1236 22 40 0.0920 6 Week 6 (study day 36 to 42) 0.132
## 1237 22 41 0.0920 6 Week 6 (study day 36 to 42) 0.132
## 1238 22 42 0.247 6 Week 6 (study day 36 to 42) 0.132
## 1239 22 43 0.247 7 Week 7 (study day 43 to 49) 0.141
## 1240 22 44 0.124 7 Week 7 (study day 43 to 49) 0.141
## 1241 22 45 0.124 7 Week 7 (study day 43 to 49) 0.141
## 1242 22 46 0.124 7 Week 7 (study day 43 to 49) 0.141
## 1243 22 47 0.124 7 Week 7 (study day 43 to 49) 0.141
## 1244 22 48 0.124 7 Week 7 (study day 43 to 49) 0.141
## 1245 22 49 0.124 7 Week 7 (study day 43 to 49) 0.141
## 1246 22 50 0.131 8 Week 8 (study day 50 to 56) 0.131
## 1247 22 51 0.131 8 Week 8 (study day 50 to 56) 0.131
## 1248 22 52 0.131 8 Week 8 (study day 50 to 56) 0.131
## 1249 22 53 0.131 8 Week 8 (study day 50 to 56) 0.131
## 1250 22 54 0.131 8 Week 8 (study day 50 to 56) 0.131
## 1251 22 55 0.131 8 Week 8 (study day 50 to 56) 0.131
## 1252 22 56 0.131 8 Week 8 (study day 50 to 56) 0.131
## 1253 23 0 0.289 0 Baseline 0.289
## 1254 23 1 0.289 1 Week 1 (study day 1 to 7) 0.243
## 1255 23 2 0.289 1 Week 1 (study day 1 to 7) 0.243
## 1256 23 3 0.282 1 Week 1 (study day 1 to 7) 0.243
## 1257 23 4 0.282 1 Week 1 (study day 1 to 7) 0.243
## 1258 23 5 0.211 1 Week 1 (study day 1 to 7) 0.243
## 1259 23 6 0.207 1 Week 1 (study day 1 to 7) 0.243
## 1260 23 7 0.138 1 Week 1 (study day 1 to 7) 0.243
## 1261 23 8 0.138 2 Week 2 (study day 8 to 14) 0.186
## 1262 23 9 0.151 2 Week 2 (study day 8 to 14) 0.186
## 1263 23 10 0.151 2 Week 2 (study day 8 to 14) 0.186
## 1264 23 11 0.113 2 Week 2 (study day 8 to 14) 0.186
## 1265 23 12 0.151 2 Week 2 (study day 8 to 14) 0.186
## 1266 23 13 0.150 2 Week 2 (study day 8 to 14) 0.186
## 1267 23 14 0.451 2 Week 2 (study day 8 to 14) 0.186
## 1268 23 15 0.301 3 Week 3 (study day 15 to 21) 1.03
## 1269 23 16 4 3 Week 3 (study day 15 to 21) 1.03
## 1270 23 17 0.593 3 Week 3 (study day 15 to 21) 1.03
## 1271 23 18 0.583 3 Week 3 (study day 15 to 21) 1.03
## 1272 23 19 0.583 3 Week 3 (study day 15 to 21) 1.03
## 1273 23 20 0.583 3 Week 3 (study day 15 to 21) 1.03
## 1274 23 21 0.582 3 Week 3 (study day 15 to 21) 1.03
## 1275 23 22 0.582 4 Week 4 (study day 22 to 28) 0.404
## 1276 23 23 0.437 4 Week 4 (study day 22 to 28) 0.404
## 1277 23 24 0.452 4 Week 4 (study day 22 to 28) 0.404
## 1278 23 25 0.452 4 Week 4 (study day 22 to 28) 0.404
## 1279 23 26 0.302 4 Week 4 (study day 22 to 28) 0.404
## 1280 23 27 0.301 4 Week 4 (study day 22 to 28) 0.404
## 1281 23 28 0.301 4 Week 4 (study day 22 to 28) 0.404
## 1282 23 29 0.301 5 Week 5 (study day 29 to 35) 0.305
## 1283 23 30 0.307 5 Week 5 (study day 29 to 35) 0.305
## 1284 23 31 0.307 5 Week 5 (study day 29 to 35) 0.305
## 1285 23 32 0.307 5 Week 5 (study day 29 to 35) 0.305
## 1286 23 33 0.307 5 Week 5 (study day 29 to 35) 0.305
## 1287 23 34 0.303 5 Week 5 (study day 29 to 35) 0.305
## 1288 23 35 0.303 5 Week 5 (study day 29 to 35) 0.305
## 1289 23 36 0.303 6 Week 6 (study day 36 to 42) 0.302
## 1290 23 37 0.303 6 Week 6 (study day 36 to 42) 0.302
## 1291 23 38 0.303 6 Week 6 (study day 36 to 42) 0.302
## 1292 23 39 0.302 6 Week 6 (study day 36 to 42) 0.302
## 1293 23 40 0.302 6 Week 6 (study day 36 to 42) 0.302
## 1294 23 41 0.302 6 Week 6 (study day 36 to 42) 0.302
## 1295 23 42 0.302 6 Week 6 (study day 36 to 42) 0.302
## 1296 23 43 0.302 7 Week 7 (study day 43 to 49) 0.465
## 1297 23 44 0.302 7 Week 7 (study day 43 to 49) 0.465
## 1298 23 45 0.603 7 Week 7 (study day 43 to 49) 0.465
## 1299 23 46 0.585 7 Week 7 (study day 43 to 49) 0.465
## 1300 23 47 0.585 7 Week 7 (study day 43 to 49) 0.465
## 1301 23 48 0.439 7 Week 7 (study day 43 to 49) 0.465
## 1302 23 49 0.439 7 Week 7 (study day 43 to 49) 0.465
## 1303 23 50 0.439 8 Week 8 (study day 50 to 56) 1.57
## 1304 23 51 0.292 8 Week 8 (study day 50 to 56) 1.57
## 1305 23 52 0.292 8 Week 8 (study day 50 to 56) 1.57
## 1306 23 53 0.292 8 Week 8 (study day 50 to 56) 1.57
## 1307 23 54 0.292 8 Week 8 (study day 50 to 56) 1.57
## 1308 23 55 7.60 8 Week 8 (study day 50 to 56) 1.57
## 1309 23 56 1.75 8 Week 8 (study day 50 to 56) 1.57
## 1310 24 0 2.37 0 Baseline 2.37
## 1311 24 1 2.37 1 Week 1 (study day 1 to 7) 18.1
## 1312 24 2 2.37 1 Week 1 (study day 1 to 7) 18.1
## 1313 24 3 39.6 1 Week 1 (study day 1 to 7) 18.1
## 1314 24 4 39.6 1 Week 1 (study day 1 to 7) 18.1
## 1315 24 5 39.6 1 Week 1 (study day 1 to 7) 18.1
## 1316 24 6 2.23 1 Week 1 (study day 1 to 7) 18.1
## 1317 24 7 1.12 1 Week 1 (study day 1 to 7) 18.1
## 1318 24 8 1.12 2 Week 2 (study day 8 to 14) 1.12
## 1319 24 9 1.16 2 Week 2 (study day 8 to 14) 1.12
## 1320 24 10 1.16 2 Week 2 (study day 8 to 14) 1.12
## 1321 24 11 1.16 2 Week 2 (study day 8 to 14) 1.12
## 1322 24 12 1.16 2 Week 2 (study day 8 to 14) 1.12
## 1323 24 13 1.16 2 Week 2 (study day 8 to 14) 1.12
## 1324 24 14 0.926 2 Week 2 (study day 8 to 14) 1.12
## 1325 24 15 0.926 3 Week 3 (study day 15 to 21) 6.22
## 1326 24 16 0.926 3 Week 3 (study day 15 to 21) 6.22
## 1327 24 17 0.926 3 Week 3 (study day 15 to 21) 6.22
## 1328 24 18 0.898 3 Week 3 (study day 15 to 21) 6.22
## 1329 24 19 0.898 3 Week 3 (study day 15 to 21) 6.22
## 1330 24 20 0.898 3 Week 3 (study day 15 to 21) 6.22
## 1331 24 21 38.1 3 Week 3 (study day 15 to 21) 6.22
## 1332 24 22 0.893 4 Week 4 (study day 22 to 28) 6.28
## 1333 24 23 0.898 4 Week 4 (study day 22 to 28) 6.28
## 1334 24 24 0.898 4 Week 4 (study day 22 to 28) 6.28
## 1335 24 25 0.898 4 Week 4 (study day 22 to 28) 6.28
## 1336 24 26 0.904 4 Week 4 (study day 22 to 28) 6.28
## 1337 24 27 38.6 4 Week 4 (study day 22 to 28) 6.28
## 1338 24 28 0.904 4 Week 4 (study day 22 to 28) 6.28
## 1339 24 29 0.904 5 Week 5 (study day 29 to 35) 0.899
## 1340 24 30 0.904 5 Week 5 (study day 29 to 35) 0.899
## 1341 24 31 0.904 5 Week 5 (study day 29 to 35) 0.899
## 1342 24 32 0.904 5 Week 5 (study day 29 to 35) 0.899
## 1343 24 33 0.904 5 Week 5 (study day 29 to 35) 0.899
## 1344 24 34 0.904 5 Week 5 (study day 29 to 35) 0.899
## 1345 24 35 0.872 5 Week 5 (study day 29 to 35) 0.899
## 1346 24 36 0.872 6 Week 6 (study day 36 to 42) 0.831
## 1347 24 37 0.872 6 Week 6 (study day 36 to 42) 0.831
## 1348 24 38 0.872 6 Week 6 (study day 36 to 42) 0.831
## 1349 24 39 0.872 6 Week 6 (study day 36 to 42) 0.831
## 1350 24 40 0.872 6 Week 6 (study day 36 to 42) 0.831
## 1351 24 41 0.872 6 Week 6 (study day 36 to 42) 0.831
## 1352 24 42 0.581 6 Week 6 (study day 36 to 42) 0.831
## 1353 24 43 0.581 7 Week 7 (study day 43 to 49) 0.552
## 1354 24 44 0.581 7 Week 7 (study day 43 to 49) 0.552
## 1355 24 45 0.581 7 Week 7 (study day 43 to 49) 0.552
## 1356 24 46 0.565 7 Week 7 (study day 43 to 49) 0.552
## 1357 24 47 0.565 7 Week 7 (study day 43 to 49) 0.552
## 1358 24 48 0.565 7 Week 7 (study day 43 to 49) 0.552
## 1359 24 49 0.424 7 Week 7 (study day 43 to 49) 0.552
## 1360 24 50 0.424 8 Week 8 (study day 50 to 56) 0.422
## 1361 24 51 0.424 8 Week 8 (study day 50 to 56) 0.422
## 1362 24 52 0.424 8 Week 8 (study day 50 to 56) 0.422
## 1363 24 53 0.420 8 Week 8 (study day 50 to 56) 0.422
## 1364 24 54 0.420 8 Week 8 (study day 50 to 56) 0.422
## 1365 24 55 0.420 8 Week 8 (study day 50 to 56) 0.422
## 1366 24 56 0.420 8 Week 8 (study day 50 to 56) 0.422
## 1367 25 0 3.52 0 Baseline 3.52
## 1368 25 1 3.52 1 Week 1 (study day 1 to 7) 3.52
## 1369 25 2 3.52 1 Week 1 (study day 1 to 7) 3.52
## 1370 25 3 3.52 1 Week 1 (study day 1 to 7) 3.52
## 1371 25 4 3.52 1 Week 1 (study day 1 to 7) 3.52
## 1372 25 5 3.52 1 Week 1 (study day 1 to 7) 3.52
## 1373 25 6 3.52 1 Week 1 (study day 1 to 7) 3.52
## 1374 25 7 3.52 1 Week 1 (study day 1 to 7) 3.52
## 1375 25 8 3.52 2 Week 2 (study day 8 to 14) 3.24
## 1376 25 9 3.52 2 Week 2 (study day 8 to 14) 3.24
## 1377 25 10 3.52 2 Week 2 (study day 8 to 14) 3.24
## 1378 25 11 3.12 2 Week 2 (study day 8 to 14) 3.24
## 1379 25 12 3.12 2 Week 2 (study day 8 to 14) 3.24
## 1380 25 13 3.12 2 Week 2 (study day 8 to 14) 3.24
## 1381 25 14 2.73 2 Week 2 (study day 8 to 14) 3.24
## 1382 25 15 2.73 3 Week 3 (study day 15 to 21) 2.64
## 1383 25 16 2.73 3 Week 3 (study day 15 to 21) 2.64
## 1384 25 17 2.58 3 Week 3 (study day 15 to 21) 2.64
## 1385 25 18 2.58 3 Week 3 (study day 15 to 21) 2.64
## 1386 25 19 2.58 3 Week 3 (study day 15 to 21) 2.64
## 1387 25 20 2.58 3 Week 3 (study day 15 to 21) 2.64
## 1388 25 21 2.68 3 Week 3 (study day 15 to 21) 2.64
## 1389 25 22 2.68 4 Week 4 (study day 22 to 28) 2.68
## 1390 25 23 2.68 4 Week 4 (study day 22 to 28) 2.68
## 1391 25 24 2.68 4 Week 4 (study day 22 to 28) 2.68
## 1392 25 25 2.68 4 Week 4 (study day 22 to 28) 2.68
## 1393 25 26 2.68 4 Week 4 (study day 22 to 28) 2.68
## 1394 25 27 2.68 4 Week 4 (study day 22 to 28) 2.68
## 1395 25 28 2.68 4 Week 4 (study day 22 to 28) 2.68
## 1396 25 29 2.68 5 Week 5 (study day 29 to 35) 2.65
## 1397 25 30 2.68 5 Week 5 (study day 29 to 35) 2.65
## 1398 25 31 2.68 5 Week 5 (study day 29 to 35) 2.65
## 1399 25 32 2.68 5 Week 5 (study day 29 to 35) 2.65
## 1400 25 33 2.68 5 Week 5 (study day 29 to 35) 2.65
## 1401 25 34 2.59 5 Week 5 (study day 29 to 35) 2.65
## 1402 25 35 2.59 5 Week 5 (study day 29 to 35) 2.65
## 1403 25 36 2.59 6 Week 6 (study day 36 to 42) 2.53
## 1404 25 37 2.59 6 Week 6 (study day 36 to 42) 2.53
## 1405 25 38 2.5 6 Week 6 (study day 36 to 42) 2.53
## 1406 25 39 2.5 6 Week 6 (study day 36 to 42) 2.53
## 1407 25 40 2.5 6 Week 6 (study day 36 to 42) 2.53
## 1408 25 41 2.5 6 Week 6 (study day 36 to 42) 2.53
## 1409 25 42 2.5 6 Week 6 (study day 36 to 42) 2.53
## 1410 25 43 2.5 7 Week 7 (study day 43 to 49) 2.39
## 1411 25 44 2.5 7 Week 7 (study day 43 to 49) 2.39
## 1412 25 45 2.5 7 Week 7 (study day 43 to 49) 2.39
## 1413 25 46 2.41 7 Week 7 (study day 43 to 49) 2.39
## 1414 25 47 2.32 7 Week 7 (study day 43 to 49) 2.39
## 1415 25 48 2.32 7 Week 7 (study day 43 to 49) 2.39
## 1416 25 49 2.14 7 Week 7 (study day 43 to 49) 2.39
## 1417 25 50 2.14 8 Week 8 (study day 50 to 56) 1.96
## 1418 25 51 1.96 8 Week 8 (study day 50 to 56) 1.96
## 1419 25 52 1.96 8 Week 8 (study day 50 to 56) 1.96
## 1420 25 53 1.96 8 Week 8 (study day 50 to 56) 1.96
## 1421 25 54 1.96 8 Week 8 (study day 50 to 56) 1.96
## 1422 25 55 1.96 8 Week 8 (study day 50 to 56) 1.96
## 1423 25 56 1.79 8 Week 8 (study day 50 to 56) 1.96
## 1424 26 0 5.25 0 Baseline 5.25
## 1425 26 1 5.26 1 Week 1 (study day 1 to 7) 4.04
## 1426 26 2 5.26 1 Week 1 (study day 1 to 7) 4.04
## 1427 26 3 5.34 1 Week 1 (study day 1 to 7) 4.04
## 1428 26 4 5.34 1 Week 1 (study day 1 to 7) 4.04
## 1429 26 5 4.21 1 Week 1 (study day 1 to 7) 4.04
## 1430 26 6 1.43 1 Week 1 (study day 1 to 7) 4.04
## 1431 26 7 1.43 1 Week 1 (study day 1 to 7) 4.04
## 1432 26 8 4 2 Week 2 (study day 8 to 14) 2.99
## 1433 26 9 2.57 2 Week 2 (study day 8 to 14) 2.99
## 1434 26 10 2.65 2 Week 2 (study day 8 to 14) 2.99
## 1435 26 11 0.294 2 Week 2 (study day 8 to 14) 2.99
## 1436 26 12 3.82 2 Week 2 (study day 8 to 14) 2.99
## 1437 26 13 3.80 2 Week 2 (study day 8 to 14) 2.99
## 1438 26 14 3.80 2 Week 2 (study day 8 to 14) 2.99
## 1439 26 15 3.80 3 Week 3 (study day 15 to 21) 4.26
## 1440 26 16 5.56 3 Week 3 (study day 15 to 21) 4.26
## 1441 26 17 5.49 3 Week 3 (study day 15 to 21) 4.26
## 1442 26 18 3.76 3 Week 3 (study day 15 to 21) 4.26
## 1443 26 19 3.76 3 Week 3 (study day 15 to 21) 4.26
## 1444 26 20 3.74 3 Week 3 (study day 15 to 21) 4.26
## 1445 26 21 3.74 3 Week 3 (study day 15 to 21) 4.26
## 1446 26 22 3.74 4 Week 4 (study day 22 to 28) 3.60
## 1447 26 23 3.74 4 Week 4 (study day 22 to 28) 3.60
## 1448 26 24 3.63 4 Week 4 (study day 22 to 28) 3.60
## 1449 26 25 3.63 4 Week 4 (study day 22 to 28) 3.60
## 1450 26 26 3.63 4 Week 4 (study day 22 to 28) 3.60
## 1451 26 27 3.71 4 Week 4 (study day 22 to 28) 3.60
## 1452 26 28 3.14 4 Week 4 (study day 22 to 28) 3.60
## 1453 26 29 3.14 5 Week 5 (study day 29 to 35) 2.79
## 1454 26 30 3.14 5 Week 5 (study day 29 to 35) 2.79
## 1455 26 31 3.12 5 Week 5 (study day 29 to 35) 2.79
## 1456 26 32 2.56 5 Week 5 (study day 29 to 35) 2.79
## 1457 26 33 2.56 5 Week 5 (study day 29 to 35) 2.79
## 1458 26 34 2.51 5 Week 5 (study day 29 to 35) 2.79
## 1459 26 35 2.51 5 Week 5 (study day 29 to 35) 2.79
## 1460 26 36 2.51 6 Week 6 (study day 36 to 42) 2.29
## 1461 26 37 2.51 6 Week 6 (study day 36 to 42) 2.29
## 1462 26 38 2.51 6 Week 6 (study day 36 to 42) 2.29
## 1463 26 39 2.51 6 Week 6 (study day 36 to 42) 2.29
## 1464 26 40 1.96 6 Week 6 (study day 36 to 42) 2.29
## 1465 26 41 2 6 Week 6 (study day 36 to 42) 2.29
## 1466 26 42 2 6 Week 6 (study day 36 to 42) 2.29
## 1467 26 43 1.36 7 Week 7 (study day 43 to 49) 1.07
## 1468 26 44 1.36 7 Week 7 (study day 43 to 49) 1.07
## 1469 26 45 1.09 7 Week 7 (study day 43 to 49) 1.07
## 1470 26 46 0.956 7 Week 7 (study day 43 to 49) 1.07
## 1471 26 47 0.956 7 Week 7 (study day 43 to 49) 1.07
## 1472 26 48 0.962 7 Week 7 (study day 43 to 49) 1.07
## 1473 26 49 0.824 7 Week 7 (study day 43 to 49) 1.07
## 1474 26 50 0.824 8 Week 8 (study day 50 to 56) 0.719
## 1475 26 51 0.824 8 Week 8 (study day 50 to 56) 0.719
## 1476 26 52 0.811 8 Week 8 (study day 50 to 56) 0.719
## 1477 26 53 0.676 8 Week 8 (study day 50 to 56) 0.719
## 1478 26 54 0.676 8 Week 8 (study day 50 to 56) 0.719
## 1479 26 55 0.679 8 Week 8 (study day 50 to 56) 0.719
## 1480 26 56 0.543 8 Week 8 (study day 50 to 56) 0.719
## 1481 27 0 2.97 0 Baseline 2.97
## 1482 27 1 2.97 1 Week 1 (study day 1 to 7) 2.94
## 1483 27 2 2.97 1 Week 1 (study day 1 to 7) 2.94
## 1484 27 3 2.97 1 Week 1 (study day 1 to 7) 2.94
## 1485 27 4 2.97 1 Week 1 (study day 1 to 7) 2.94
## 1486 27 5 2.97 1 Week 1 (study day 1 to 7) 2.94
## 1487 27 6 3.64 1 Week 1 (study day 1 to 7) 2.94
## 1488 27 7 2.08 1 Week 1 (study day 1 to 7) 2.94
## 1489 27 8 0.667 2 Week 2 (study day 8 to 14) 0.720
## 1490 27 9 1.25 2 Week 2 (study day 8 to 14) 0.720
## 1491 27 10 0.625 2 Week 2 (study day 8 to 14) 0.720
## 1492 27 11 0.625 2 Week 2 (study day 8 to 14) 0.720
## 1493 27 12 0.625 2 Week 2 (study day 8 to 14) 0.720
## 1494 27 13 0.625 2 Week 2 (study day 8 to 14) 0.720
## 1495 27 14 0.625 2 Week 2 (study day 8 to 14) 0.720
## 1496 27 15 0.606 3 Week 3 (study day 15 to 21) 0.766
## 1497 27 16 0.606 3 Week 3 (study day 15 to 21) 0.766
## 1498 27 17 0.606 3 Week 3 (study day 15 to 21) 0.766
## 1499 27 18 0.625 3 Week 3 (study day 15 to 21) 0.766
## 1500 27 19 1.25 3 Week 3 (study day 15 to 21) 0.766
## 1501 27 20 0.625 3 Week 3 (study day 15 to 21) 0.766
## 1502 27 21 1.04 3 Week 3 (study day 15 to 21) 0.766
## 1503 27 22 0.408 4 Week 4 (study day 22 to 28) 0.262
## 1504 27 23 0.663 4 Week 4 (study day 22 to 28) 0.262
## 1505 27 24 0.255 4 Week 4 (study day 22 to 28) 0.262
## 1506 27 25 0.255 4 Week 4 (study day 22 to 28) 0.262
## 1507 27 26 0.255 4 Week 4 (study day 22 to 28) 0.262
## 1508 27 27 0 4 Week 4 (study day 22 to 28) 0.262
## 1509 27 28 0 4 Week 4 (study day 22 to 28) 0.262
## 1510 27 29 0.204 5 Week 5 (study day 29 to 35) 0.204
## 1511 27 30 0.204 5 Week 5 (study day 29 to 35) 0.204
## 1512 27 31 0.204 5 Week 5 (study day 29 to 35) 0.204
## 1513 27 32 0.204 5 Week 5 (study day 29 to 35) 0.204
## 1514 27 33 0.204 5 Week 5 (study day 29 to 35) 0.204
## 1515 27 34 0.204 5 Week 5 (study day 29 to 35) 0.204
## 1516 27 35 0.204 5 Week 5 (study day 29 to 35) 0.204
## 1517 27 36 0.204 6 Week 6 (study day 36 to 42) 0.175
## 1518 27 37 0.204 6 Week 6 (study day 36 to 42) 0.175
## 1519 27 38 0.204 6 Week 6 (study day 36 to 42) 0.175
## 1520 27 39 0.204 6 Week 6 (study day 36 to 42) 0.175
## 1521 27 40 0.204 6 Week 6 (study day 36 to 42) 0.175
## 1522 27 41 0.204 6 Week 6 (study day 36 to 42) 0.175
## 1523 27 42 0 6 Week 6 (study day 36 to 42) 0.175
## 1524 27 43 0 7 Week 7 (study day 43 to 49) 0.0377
## 1525 27 44 0 7 Week 7 (study day 43 to 49) 0.0377
## 1526 27 45 0 7 Week 7 (study day 43 to 49) 0.0377
## 1527 27 46 0 7 Week 7 (study day 43 to 49) 0.0377
## 1528 27 47 0 7 Week 7 (study day 43 to 49) 0.0377
## 1529 27 48 0.132 7 Week 7 (study day 43 to 49) 0.0377
## 1530 27 49 0.132 7 Week 7 (study day 43 to 49) 0.0377
## 1531 27 50 0.132 8 Week 8 (study day 50 to 56) 0.156
## 1532 27 51 0.132 8 Week 8 (study day 50 to 56) 0.156
## 1533 27 52 0.135 8 Week 8 (study day 50 to 56) 0.156
## 1534 27 53 0.135 8 Week 8 (study day 50 to 56) 0.156
## 1535 27 54 0.231 8 Week 8 (study day 50 to 56) 0.156
## 1536 27 55 0.231 8 Week 8 (study day 50 to 56) 0.156
## 1537 27 56 0.0962 8 Week 8 (study day 50 to 56) 0.156
## 1538 28 0 37.5 0 Baseline 37.5
## 1539 28 1 37.5 1 Week 1 (study day 1 to 7) 22.6
## 1540 28 2 37.5 1 Week 1 (study day 1 to 7) 22.6
## 1541 28 3 37.5 1 Week 1 (study day 1 to 7) 22.6
## 1542 28 4 39.7 1 Week 1 (study day 1 to 7) 22.6
## 1543 28 5 2.16 1 Week 1 (study day 1 to 7) 22.6
## 1544 28 6 1.88 1 Week 1 (study day 1 to 7) 22.6
## 1545 28 7 1.88 1 Week 1 (study day 1 to 7) 22.6
## 1546 28 8 1.88 2 Week 2 (study day 8 to 14) 1.81
## 1547 28 9 1.86 2 Week 2 (study day 8 to 14) 1.81
## 1548 28 10 1.86 2 Week 2 (study day 8 to 14) 1.81
## 1549 28 11 1.86 2 Week 2 (study day 8 to 14) 1.81
## 1550 28 12 1.88 2 Week 2 (study day 8 to 14) 1.81
## 1551 28 13 1.67 2 Week 2 (study day 8 to 14) 1.81
## 1552 28 14 1.67 2 Week 2 (study day 8 to 14) 1.81
## 1553 28 15 1.65 3 Week 3 (study day 15 to 21) 1.65
## 1554 28 16 1.65 3 Week 3 (study day 15 to 21) 1.65
## 1555 28 17 1.65 3 Week 3 (study day 15 to 21) 1.65
## 1556 28 18 1.65 3 Week 3 (study day 15 to 21) 1.65
## 1557 28 19 1.65 3 Week 3 (study day 15 to 21) 1.65
## 1558 28 20 1.65 3 Week 3 (study day 15 to 21) 1.65
## 1559 28 21 1.65 3 Week 3 (study day 15 to 21) 1.65
## 1560 28 22 1.68 4 Week 4 (study day 22 to 28) 1.68
## 1561 28 23 1.68 4 Week 4 (study day 22 to 28) 1.68
## 1562 28 24 1.68 4 Week 4 (study day 22 to 28) 1.68
## 1563 28 25 1.68 4 Week 4 (study day 22 to 28) 1.68
## 1564 28 26 1.68 4 Week 4 (study day 22 to 28) 1.68
## 1565 28 27 1.68 4 Week 4 (study day 22 to 28) 1.68
## 1566 28 28 1.68 4 Week 4 (study day 22 to 28) 1.68
## 1567 28 29 1.68 5 Week 5 (study day 29 to 35) 1.68
## 1568 28 30 1.68 5 Week 5 (study day 29 to 35) 1.68
## 1569 28 31 1.68 5 Week 5 (study day 29 to 35) 1.68
## 1570 28 32 1.68 5 Week 5 (study day 29 to 35) 1.68
## 1571 28 33 1.68 5 Week 5 (study day 29 to 35) 1.68
## 1572 28 34 1.68 5 Week 5 (study day 29 to 35) 1.68
## 1573 28 35 1.68 5 Week 5 (study day 29 to 35) 1.68
## 1574 28 36 1.68 6 Week 6 (study day 36 to 42) 1.53
## 1575 28 37 1.68 6 Week 6 (study day 36 to 42) 1.53
## 1576 28 38 1.47 6 Week 6 (study day 36 to 42) 1.53
## 1577 28 39 1.47 6 Week 6 (study day 36 to 42) 1.53
## 1578 28 40 1.47 6 Week 6 (study day 36 to 42) 1.53
## 1579 28 41 1.47 6 Week 6 (study day 36 to 42) 1.53
## 1580 28 42 1.45 6 Week 6 (study day 36 to 42) 1.53
## 1581 28 43 1.45 7 Week 7 (study day 43 to 49) 1.32
## 1582 28 44 1.45 7 Week 7 (study day 43 to 49) 1.32
## 1583 28 45 1.45 7 Week 7 (study day 43 to 49) 1.32
## 1584 28 46 1.24 7 Week 7 (study day 43 to 49) 1.32
## 1585 28 47 1.24 7 Week 7 (study day 43 to 49) 1.32
## 1586 28 48 1.21 7 Week 7 (study day 43 to 49) 1.32
## 1587 28 49 1.21 7 Week 7 (study day 43 to 49) 1.32
## 1588 28 50 1.21 8 Week 8 (study day 50 to 56) 1.10
## 1589 28 51 1.21 8 Week 8 (study day 50 to 56) 1.10
## 1590 28 52 1.21 8 Week 8 (study day 50 to 56) 1.10
## 1591 28 53 1.01 8 Week 8 (study day 50 to 56) 1.10
## 1592 28 54 1.01 8 Week 8 (study day 50 to 56) 1.10
## 1593 28 55 1.01 8 Week 8 (study day 50 to 56) 1.10
## 1594 28 56 1.03 8 Week 8 (study day 50 to 56) 1.10
## 1595 29 0 37.5 0 Baseline 37.5
## 1596 29 1 37.5 1 Week 1 (study day 1 to 7) 12.4
## 1597 29 2 39.4 1 Week 1 (study day 1 to 7) 12.4
## 1598 29 3 1.94 1 Week 1 (study day 1 to 7) 12.4
## 1599 29 4 1.94 1 Week 1 (study day 1 to 7) 12.4
## 1600 29 5 1.94 1 Week 1 (study day 1 to 7) 12.4
## 1601 29 6 1.86 1 Week 1 (study day 1 to 7) 12.4
## 1602 29 7 1.86 1 Week 1 (study day 1 to 7) 12.4
## 1603 29 8 1.86 2 Week 2 (study day 8 to 14) 22.8
## 1604 29 9 1.86 2 Week 2 (study day 8 to 14) 22.8
## 1605 29 10 1.86 2 Week 2 (study day 8 to 14) 22.8
## 1606 29 11 39.4 2 Week 2 (study day 8 to 14) 22.8
## 1607 29 12 39.4 2 Week 2 (study day 8 to 14) 22.8
## 1608 29 13 37.5 2 Week 2 (study day 8 to 14) 22.8
## 1609 29 14 37.5 2 Week 2 (study day 8 to 14) 22.8
## 1610 29 15 37.5 3 Week 3 (study day 15 to 21) 7.40
## 1611 29 16 2.32 3 Week 3 (study day 15 to 21) 7.40
## 1612 29 17 2.37 3 Week 3 (study day 15 to 21) 7.40
## 1613 29 18 2.37 3 Week 3 (study day 15 to 21) 7.40
## 1614 29 19 2.37 3 Week 3 (study day 15 to 21) 7.40
## 1615 29 20 2.44 3 Week 3 (study day 15 to 21) 7.40
## 1616 29 21 2.44 3 Week 3 (study day 15 to 21) 7.40
## 1617 29 22 2.44 4 Week 4 (study day 22 to 28) 23.7
## 1618 29 23 2.27 4 Week 4 (study day 22 to 28) 23.7
## 1619 29 24 2.27 4 Week 4 (study day 22 to 28) 23.7
## 1620 29 25 39.8 4 Week 4 (study day 22 to 28) 23.7
## 1621 29 26 39.8 4 Week 4 (study day 22 to 28) 23.7
## 1622 29 27 39.8 4 Week 4 (study day 22 to 28) 23.7
## 1623 29 28 39.8 4 Week 4 (study day 22 to 28) 23.7
## 1624 29 29 2.25 5 Week 5 (study day 29 to 35) 2.25
## 1625 29 30 2.25 5 Week 5 (study day 29 to 35) 2.25
## 1626 29 31 2.25 5 Week 5 (study day 29 to 35) 2.25
## 1627 29 32 2.26 5 Week 5 (study day 29 to 35) 2.25
## 1628 29 33 2.26 5 Week 5 (study day 29 to 35) 2.25
## 1629 29 34 2.26 5 Week 5 (study day 29 to 35) 2.25
## 1630 29 35 2.20 5 Week 5 (study day 29 to 35) 2.25
## 1631 29 36 2.20 6 Week 6 (study day 36 to 42) 2.16
## 1632 29 37 2.20 6 Week 6 (study day 36 to 42) 2.16
## 1633 29 38 2.15 6 Week 6 (study day 36 to 42) 2.16
## 1634 29 39 2.15 6 Week 6 (study day 36 to 42) 2.16
## 1635 29 40 2.15 6 Week 6 (study day 36 to 42) 2.16
## 1636 29 41 2.15 6 Week 6 (study day 36 to 42) 2.16
## 1637 29 42 2.15 6 Week 6 (study day 36 to 42) 2.16
## 1638 29 43 2.15 7 Week 7 (study day 43 to 49) 2.12
## 1639 29 44 2.15 7 Week 7 (study day 43 to 49) 2.12
## 1640 29 45 2.15 7 Week 7 (study day 43 to 49) 2.12
## 1641 29 46 2.15 7 Week 7 (study day 43 to 49) 2.12
## 1642 29 47 2.15 7 Week 7 (study day 43 to 49) 2.12
## 1643 29 48 2.15 7 Week 7 (study day 43 to 49) 2.12
## 1644 29 49 1.98 7 Week 7 (study day 43 to 49) 2.12
## 1645 29 50 1.98 8 Week 8 (study day 50 to 56) 1.98
## 1646 29 51 3.63 8 Week 8 (study day 50 to 56) 1.98
## 1647 29 52 1.65 8 Week 8 (study day 50 to 56) 1.98
## 1648 29 53 1.65 8 Week 8 (study day 50 to 56) 1.98
## 1649 29 54 1.65 8 Week 8 (study day 50 to 56) 1.98
## 1650 29 55 1.65 8 Week 8 (study day 50 to 56) 1.98
## 1651 29 56 1.65 8 Week 8 (study day 50 to 56) 1.98
## 1652 30 0 32.1 0 Baseline 32.1
## 1653 30 1 32.1 1 Week 1 (study day 1 to 7) 2.76
## 1654 30 2 2.88 1 Week 1 (study day 1 to 7) 2.76
## 1655 30 3 2.78 1 Week 1 (study day 1 to 7) 2.76
## 1656 30 4 2.78 1 Week 1 (study day 1 to 7) 2.76
## 1657 30 5 2.78 1 Week 1 (study day 1 to 7) 2.76
## 1658 30 6 2.80 1 Week 1 (study day 1 to 7) 2.76
## 1659 30 7 2.64 1 Week 1 (study day 1 to 7) 2.76
## 1660 30 8 2.64 2 Week 2 (study day 8 to 14) 2.44
## 1661 30 9 2.62 2 Week 2 (study day 8 to 14) 2.44
## 1662 30 10 2.45 2 Week 2 (study day 8 to 14) 2.44
## 1663 30 11 2.45 2 Week 2 (study day 8 to 14) 2.44
## 1664 30 12 2.40 2 Week 2 (study day 8 to 14) 2.44
## 1665 30 13 2.24 2 Week 2 (study day 8 to 14) 2.44
## 1666 30 14 2.24 2 Week 2 (study day 8 to 14) 2.44
## 1667 30 15 2.33 3 Week 3 (study day 15 to 21) 2.11
## 1668 30 16 2.17 3 Week 3 (study day 15 to 21) 2.11
## 1669 30 17 2.17 3 Week 3 (study day 15 to 21) 2.11
## 1670 30 18 2.14 3 Week 3 (study day 15 to 21) 2.11
## 1671 30 19 1.98 3 Week 3 (study day 15 to 21) 2.11
## 1672 30 20 1.98 3 Week 3 (study day 15 to 21) 2.11
## 1673 30 21 1.98 3 Week 3 (study day 15 to 21) 2.11
## 1674 30 22 1.98 4 Week 4 (study day 22 to 28) 1.57
## 1675 30 23 0 4 Week 4 (study day 22 to 28) 1.57
## 1676 30 24 1.81 4 Week 4 (study day 22 to 28) 1.57
## 1677 30 25 1.81 4 Week 4 (study day 22 to 28) 1.57
## 1678 30 26 1.81 4 Week 4 (study day 22 to 28) 1.57
## 1679 30 27 1.81 4 Week 4 (study day 22 to 28) 1.57
## 1680 30 28 1.79 4 Week 4 (study day 22 to 28) 1.57
## 1681 30 29 1.62 5 Week 5 (study day 29 to 35) 1.52
## 1682 30 30 1.62 5 Week 5 (study day 29 to 35) 1.52
## 1683 30 31 1.62 5 Week 5 (study day 29 to 35) 1.52
## 1684 30 32 1.46 5 Week 5 (study day 29 to 35) 1.52
## 1685 30 33 1.46 5 Week 5 (study day 29 to 35) 1.52
## 1686 30 34 1.44 5 Week 5 (study day 29 to 35) 1.52
## 1687 30 35 1.44 5 Week 5 (study day 29 to 35) 1.52
## 1688 30 36 1.44 6 Week 6 (study day 36 to 42) 1.28
## 1689 30 37 1.28 6 Week 6 (study day 36 to 42) 1.28
## 1690 30 38 1.28 6 Week 6 (study day 36 to 42) 1.28
## 1691 30 39 1.28 6 Week 6 (study day 36 to 42) 1.28
## 1692 30 40 1.28 6 Week 6 (study day 36 to 42) 1.28
## 1693 30 41 1.27 6 Week 6 (study day 36 to 42) 1.28
## 1694 30 42 1.11 6 Week 6 (study day 36 to 42) 1.28
## 1695 30 43 1.11 7 Week 7 (study day 43 to 49) 0.996
## 1696 30 44 1.11 7 Week 7 (study day 43 to 49) 0.996
## 1697 30 45 0.952 7 Week 7 (study day 43 to 49) 0.996
## 1698 30 46 0.952 7 Week 7 (study day 43 to 49) 0.996
## 1699 30 47 0.952 7 Week 7 (study day 43 to 49) 0.996
## 1700 30 48 0.949 7 Week 7 (study day 43 to 49) 0.996
## 1701 30 49 0.949 7 Week 7 (study day 43 to 49) 0.996
## 1702 30 50 0.791 8 Week 8 (study day 50 to 56) 0.744
## 1703 30 51 0.791 8 Week 8 (study day 50 to 56) 0.744
## 1704 30 52 0.791 8 Week 8 (study day 50 to 56) 0.744
## 1705 30 53 0.791 8 Week 8 (study day 50 to 56) 0.744
## 1706 30 54 0.791 8 Week 8 (study day 50 to 56) 0.744
## 1707 30 55 0.633 8 Week 8 (study day 50 to 56) 0.744
## 1708 30 56 0.622 8 Week 8 (study day 50 to 56) 0.744
## 1709 31 0 2.06 0 Baseline 2.06
## 1710 31 1 2.08 1 Week 1 (study day 1 to 7) 2.08
## 1711 31 2 2.08 1 Week 1 (study day 1 to 7) 2.08
## 1712 31 3 2.08 1 Week 1 (study day 1 to 7) 2.08
## 1713 31 4 2.08 1 Week 1 (study day 1 to 7) 2.08
## 1714 31 5 2.08 1 Week 1 (study day 1 to 7) 2.08
## 1715 31 6 2.08 1 Week 1 (study day 1 to 7) 2.08
## 1716 31 7 2.08 1 Week 1 (study day 1 to 7) 2.08
## 1717 31 8 2.08 2 Week 2 (study day 8 to 14) 2.04
## 1718 31 9 2.08 2 Week 2 (study day 8 to 14) 2.04
## 1719 31 10 3.75 2 Week 2 (study day 8 to 14) 2.04
## 1720 31 11 1.67 2 Week 2 (study day 8 to 14) 2.04
## 1721 31 12 1.67 2 Week 2 (study day 8 to 14) 2.04
## 1722 31 13 1.5 2 Week 2 (study day 8 to 14) 2.04
## 1723 31 14 1.5 2 Week 2 (study day 8 to 14) 2.04
## 1724 31 15 1.5 3 Week 3 (study day 15 to 21) 1.30
## 1725 31 16 1.33 3 Week 3 (study day 15 to 21) 1.30
## 1726 31 17 1.33 3 Week 3 (study day 15 to 21) 1.30
## 1727 31 18 1.33 3 Week 3 (study day 15 to 21) 1.30
## 1728 31 19 1.30 3 Week 3 (study day 15 to 21) 1.30
## 1729 31 20 1.14 3 Week 3 (study day 15 to 21) 1.30
## 1730 31 21 1.14 3 Week 3 (study day 15 to 21) 1.30
## 1731 31 22 1.13 4 Week 4 (study day 22 to 28) 1.01
## 1732 31 23 1.13 4 Week 4 (study day 22 to 28) 1.01
## 1733 31 24 1.13 4 Week 4 (study day 22 to 28) 1.01
## 1734 31 25 0.968 4 Week 4 (study day 22 to 28) 1.01
## 1735 31 26 0.962 4 Week 4 (study day 22 to 28) 1.01
## 1736 31 27 0.962 4 Week 4 (study day 22 to 28) 1.01
## 1737 31 28 0.801 4 Week 4 (study day 22 to 28) 1.01
## 1738 31 29 0.781 5 Week 5 (study day 29 to 35) 0.781
## 1739 31 30 0.781 5 Week 5 (study day 29 to 35) 0.781
## 1740 31 31 1.41 5 Week 5 (study day 29 to 35) 0.781
## 1741 31 32 0.625 5 Week 5 (study day 29 to 35) 0.781
## 1742 31 33 0.625 5 Week 5 (study day 29 to 35) 0.781
## 1743 31 34 0.623 5 Week 5 (study day 29 to 35) 0.781
## 1744 31 35 0.623 5 Week 5 (study day 29 to 35) 0.781
## 1745 31 36 0.467 6 Week 6 (study day 36 to 42) 0.414
## 1746 31 37 0.467 6 Week 6 (study day 36 to 42) 0.414
## 1747 31 38 0.467 6 Week 6 (study day 36 to 42) 0.414
## 1748 31 39 0.467 6 Week 6 (study day 36 to 42) 0.414
## 1749 31 40 0.467 6 Week 6 (study day 36 to 42) 0.414
## 1750 31 41 0.282 6 Week 6 (study day 36 to 42) 0.414
## 1751 31 42 0.282 6 Week 6 (study day 36 to 42) 0.414
## 1752 31 43 0.282 7 Week 7 (study day 43 to 49) 0.258
## 1753 31 44 0.282 7 Week 7 (study day 43 to 49) 0.258
## 1754 31 45 0.282 7 Week 7 (study day 43 to 49) 0.258
## 1755 31 46 0.282 7 Week 7 (study day 43 to 49) 0.258
## 1756 31 47 0.227 7 Week 7 (study day 43 to 49) 0.258
## 1757 31 48 0.227 7 Week 7 (study day 43 to 49) 0.258
## 1758 31 49 0.227 7 Week 7 (study day 43 to 49) 0.258
## 1759 31 50 0.227 8 Week 8 (study day 50 to 56) 0.227
## 1760 31 51 0.227 8 Week 8 (study day 50 to 56) 0.227
## 1761 31 52 0.227 8 Week 8 (study day 50 to 56) 0.227
## 1762 31 53 0.227 8 Week 8 (study day 50 to 56) 0.227
## 1763 31 54 0.227 8 Week 8 (study day 50 to 56) 0.227
## 1764 31 55 0.227 8 Week 8 (study day 50 to 56) 0.227
## 1765 31 56 0.227 8 Week 8 (study day 50 to 56) 0.227
## 1766 32 0 17.9 0 Baseline 17.9
## 1767 32 1 17.9 1 Week 1 (study day 1 to 7) 13.1
## 1768 32 2 17.9 1 Week 1 (study day 1 to 7) 13.1
## 1769 32 3 17.9 1 Week 1 (study day 1 to 7) 13.1
## 1770 32 4 17.9 1 Week 1 (study day 1 to 7) 13.1
## 1771 32 5 8.93 1 Week 1 (study day 1 to 7) 13.1
## 1772 32 6 8.93 1 Week 1 (study day 1 to 7) 13.1
## 1773 32 7 2.68 1 Week 1 (study day 1 to 7) 13.1
## 1774 32 8 2.68 2 Week 2 (study day 8 to 14) 2.68
## 1775 32 9 2.68 2 Week 2 (study day 8 to 14) 2.68
## 1776 32 10 2.68 2 Week 2 (study day 8 to 14) 2.68
## 1777 32 11 2.68 2 Week 2 (study day 8 to 14) 2.68
## 1778 32 12 2.68 2 Week 2 (study day 8 to 14) 2.68
## 1779 32 13 2.68 2 Week 2 (study day 8 to 14) 2.68
## 1780 32 14 2.68 2 Week 2 (study day 8 to 14) 2.68
## 1781 32 15 2.68 3 Week 3 (study day 15 to 21) 2.45
## 1782 32 16 2.5 3 Week 3 (study day 15 to 21) 2.45
## 1783 32 17 2.5 3 Week 3 (study day 15 to 21) 2.45
## 1784 32 18 2.5 3 Week 3 (study day 15 to 21) 2.45
## 1785 32 19 2.32 3 Week 3 (study day 15 to 21) 2.45
## 1786 32 20 2.32 3 Week 3 (study day 15 to 21) 2.45
## 1787 32 21 2.32 3 Week 3 (study day 15 to 21) 2.45
## 1788 32 22 2.32 4 Week 4 (study day 22 to 28) 2.07
## 1789 32 23 2.14 4 Week 4 (study day 22 to 28) 2.07
## 1790 32 24 2.14 4 Week 4 (study day 22 to 28) 2.07
## 1791 32 25 2.14 4 Week 4 (study day 22 to 28) 2.07
## 1792 32 26 1.96 4 Week 4 (study day 22 to 28) 2.07
## 1793 32 27 1.96 4 Week 4 (study day 22 to 28) 2.07
## 1794 32 28 1.79 4 Week 4 (study day 22 to 28) 2.07
## 1795 32 29 1.79 5 Week 5 (study day 29 to 35) 1.71
## 1796 32 30 1.79 5 Week 5 (study day 29 to 35) 1.71
## 1797 32 31 1.79 5 Week 5 (study day 29 to 35) 1.71
## 1798 32 32 1.79 5 Week 5 (study day 29 to 35) 1.71
## 1799 32 33 1.61 5 Week 5 (study day 29 to 35) 1.71
## 1800 32 34 1.61 5 Week 5 (study day 29 to 35) 1.71
## 1801 32 35 1.61 5 Week 5 (study day 29 to 35) 1.71
## 1802 32 36 1.61 6 Week 6 (study day 36 to 42) 1.48
## 1803 32 37 1.61 6 Week 6 (study day 36 to 42) 1.48
## 1804 32 38 1.43 6 Week 6 (study day 36 to 42) 1.48
## 1805 32 39 1.43 6 Week 6 (study day 36 to 42) 1.48
## 1806 32 40 1.43 6 Week 6 (study day 36 to 42) 1.48
## 1807 32 41 1.43 6 Week 6 (study day 36 to 42) 1.48
## 1808 32 42 1.43 6 Week 6 (study day 36 to 42) 1.48
## 1809 32 43 1.25 7 Week 7 (study day 43 to 49) 1.22
## 1810 32 44 1.25 7 Week 7 (study day 43 to 49) 1.22
## 1811 32 45 1.25 7 Week 7 (study day 43 to 49) 1.22
## 1812 32 46 1.25 7 Week 7 (study day 43 to 49) 1.22
## 1813 32 47 1.25 7 Week 7 (study day 43 to 49) 1.22
## 1814 32 48 1.16 7 Week 7 (study day 43 to 49) 1.22
## 1815 32 49 1.16 7 Week 7 (study day 43 to 49) 1.22
## 1816 32 50 1.16 8 Week 8 (study day 50 to 56) 1.08
## 1817 32 51 1.07 8 Week 8 (study day 50 to 56) 1.08
## 1818 32 52 1.07 8 Week 8 (study day 50 to 56) 1.08
## 1819 32 53 1.07 8 Week 8 (study day 50 to 56) 1.08
## 1820 32 54 1.07 8 Week 8 (study day 50 to 56) 1.08
## 1821 32 55 1.07 8 Week 8 (study day 50 to 56) 1.08
## 1822 32 56 1.07 8 Week 8 (study day 50 to 56) 1.08
## 1823 33 0 0 0 Baseline 0
## 1824 33 1 17.6 1 Week 1 (study day 1 to 7) 1.89
## 1825 33 2 17.6 1 Week 1 (study day 1 to 7) 1.89
## 1826 33 3 17.6 1 Week 1 (study day 1 to 7) 1.89
## 1827 33 4 0 1 Week 1 (study day 1 to 7) 1.89
## 1828 33 5 10.8 1 Week 1 (study day 1 to 7) 1.89
## 1829 33 6 10.8 1 Week 1 (study day 1 to 7) 1.89
## 1830 33 7 1.94 1 Week 1 (study day 1 to 7) 1.89
## 1831 33 8 1.94 2 Week 2 (study day 8 to 14) 1.63
## 1832 33 9 1.94 2 Week 2 (study day 8 to 14) 1.63
## 1833 33 10 1.94 2 Week 2 (study day 8 to 14) 1.63
## 1834 33 11 1.94 2 Week 2 (study day 8 to 14) 1.63
## 1835 33 12 1.93 2 Week 2 (study day 8 to 14) 1.63
## 1836 33 13 1.93 2 Week 2 (study day 8 to 14) 1.63
## 1837 33 14 1.93 2 Week 2 (study day 8 to 14) 1.63
## 1838 33 15 1.93 3 Week 3 (study day 15 to 21) 1.27
## 1839 33 16 1.93 3 Week 3 (study day 15 to 21) 1.27
## 1840 33 17 1.93 3 Week 3 (study day 15 to 21) 1.27
## 1841 33 18 1.93 3 Week 3 (study day 15 to 21) 1.27
## 1842 33 19 1.93 3 Week 3 (study day 15 to 21) 1.27
## 1843 33 20 1.92 3 Week 3 (study day 15 to 21) 1.27
## 1844 33 21 1.92 3 Week 3 (study day 15 to 21) 1.27
## 1845 33 22 1.26 4 Week 4 (study day 22 to 28) 1.30
## 1846 33 23 1.26 4 Week 4 (study day 22 to 28) 1.30
## 1847 33 24 1.19 4 Week 4 (study day 22 to 28) 1.30
## 1848 33 25 2.24 4 Week 4 (study day 22 to 28) 1.30
## 1849 33 26 1.04 4 Week 4 (study day 22 to 28) 1.30
## 1850 33 27 1.04 4 Week 4 (study day 22 to 28) 1.30
## 1851 33 28 1.04 4 Week 4 (study day 22 to 28) 1.30
## 1852 33 29 1.04 5 Week 5 (study day 29 to 35) 1.05
## 1853 33 30 1.04 5 Week 5 (study day 29 to 35) 1.05
## 1854 33 31 1.04 5 Week 5 (study day 29 to 35) 1.05
## 1855 33 32 1.04 5 Week 5 (study day 29 to 35) 1.05
## 1856 33 33 1.06 5 Week 5 (study day 29 to 35) 1.05
## 1857 33 34 1.06 5 Week 5 (study day 29 to 35) 1.05
## 1858 33 35 1.06 5 Week 5 (study day 29 to 35) 1.05
## 1859 33 36 0.909 6 Week 6 (study day 36 to 42) 0.909
## 1860 33 37 0.909 6 Week 6 (study day 36 to 42) 0.909
## 1861 33 38 0.909 6 Week 6 (study day 36 to 42) 0.909
## 1862 33 39 0.909 6 Week 6 (study day 36 to 42) 0.909
## 1863 33 40 0.909 6 Week 6 (study day 36 to 42) 0.909
## 1864 33 41 0.909 6 Week 6 (study day 36 to 42) 0.909
## 1865 33 42 0.909 6 Week 6 (study day 36 to 42) 0.909
## 1866 33 43 0.758 7 Week 7 (study day 43 to 49) 0.731
## 1867 33 44 0.758 7 Week 7 (study day 43 to 49) 0.731
## 1868 33 45 0.758 7 Week 7 (study day 43 to 49) 0.731
## 1869 33 46 0.758 7 Week 7 (study day 43 to 49) 0.731
## 1870 33 47 0.696 7 Week 7 (study day 43 to 49) 0.731
## 1871 33 48 0.696 7 Week 7 (study day 43 to 49) 0.731
## 1872 33 49 0.696 7 Week 7 (study day 43 to 49) 0.731
## 1873 33 50 0.696 8 Week 8 (study day 50 to 56) 0.577
## 1874 33 51 0.557 8 Week 8 (study day 50 to 56) 0.577
## 1875 33 52 0.557 8 Week 8 (study day 50 to 56) 0.577
## 1876 33 53 0.557 8 Week 8 (study day 50 to 56) 0.577
## 1877 33 54 0.557 8 Week 8 (study day 50 to 56) 0.577
## 1878 33 55 0.557 8 Week 8 (study day 50 to 56) 0.577
## 1879 33 56 0.557 8 Week 8 (study day 50 to 56) 0.577
## 1880 34 0 3.18 0 Baseline 3.18
## 1881 34 1 3.18 1 Week 1 (study day 1 to 7) 3.19
## 1882 34 2 3.18 1 Week 1 (study day 1 to 7) 3.19
## 1883 34 3 3.17 1 Week 1 (study day 1 to 7) 3.19
## 1884 34 4 3.17 1 Week 1 (study day 1 to 7) 3.19
## 1885 34 5 3.17 1 Week 1 (study day 1 to 7) 3.19
## 1886 34 6 3.21 1 Week 1 (study day 1 to 7) 3.19
## 1887 34 7 3.21 1 Week 1 (study day 1 to 7) 3.19
## 1888 34 8 3.21 2 Week 2 (study day 8 to 14) 2.79
## 1889 34 9 3.21 2 Week 2 (study day 8 to 14) 2.79
## 1890 34 10 3.79 2 Week 2 (study day 8 to 14) 2.79
## 1891 34 11 2.33 2 Week 2 (study day 8 to 14) 2.79
## 1892 34 12 2.33 2 Week 2 (study day 8 to 14) 2.79
## 1893 34 13 2.33 2 Week 2 (study day 8 to 14) 2.79
## 1894 34 14 2.33 2 Week 2 (study day 8 to 14) 2.79
## 1895 34 15 2.33 3 Week 3 (study day 15 to 21) 2.33
## 1896 34 16 2.33 3 Week 3 (study day 15 to 21) 2.33
## 1897 34 17 2.33 3 Week 3 (study day 15 to 21) 2.33
## 1898 34 18 2.33 3 Week 3 (study day 15 to 21) 2.33
## 1899 34 19 2.33 3 Week 3 (study day 15 to 21) 2.33
## 1900 34 20 2.33 3 Week 3 (study day 15 to 21) 2.33
## 1901 34 21 2.33 3 Week 3 (study day 15 to 21) 2.33
## 1902 34 22 2.35 4 Week 4 (study day 22 to 28) 2.35
## 1903 34 23 2.35 4 Week 4 (study day 22 to 28) 2.35
## 1904 34 24 2.35 4 Week 4 (study day 22 to 28) 2.35
## 1905 34 25 2.35 4 Week 4 (study day 22 to 28) 2.35
## 1906 34 26 2.35 4 Week 4 (study day 22 to 28) 2.35
## 1907 34 27 2.35 4 Week 4 (study day 22 to 28) 2.35
## 1908 34 28 2.35 4 Week 4 (study day 22 to 28) 2.35
## 1909 34 29 4.40 5 Week 5 (study day 29 to 35) 2.22
## 1910 34 30 2.05 5 Week 5 (study day 29 to 35) 2.22
## 1911 34 31 2.05 5 Week 5 (study day 29 to 35) 2.22
## 1912 34 32 1.76 5 Week 5 (study day 29 to 35) 2.22
## 1913 34 33 1.76 5 Week 5 (study day 29 to 35) 2.22
## 1914 34 34 1.76 5 Week 5 (study day 29 to 35) 2.22
## 1915 34 35 1.76 5 Week 5 (study day 29 to 35) 2.22
## 1916 34 36 1.76 6 Week 6 (study day 36 to 42) 1.70
## 1917 34 37 1.76 6 Week 6 (study day 36 to 42) 1.70
## 1918 34 38 1.76 6 Week 6 (study day 36 to 42) 1.70
## 1919 34 39 1.73 6 Week 6 (study day 36 to 42) 1.70
## 1920 34 40 1.73 6 Week 6 (study day 36 to 42) 1.70
## 1921 34 41 1.73 6 Week 6 (study day 36 to 42) 1.70
## 1922 34 42 1.44 6 Week 6 (study day 36 to 42) 1.70
## 1923 34 43 1.44 7 Week 7 (study day 43 to 49) 1.23
## 1924 34 44 1.44 7 Week 7 (study day 43 to 49) 1.23
## 1925 34 45 1.44 7 Week 7 (study day 43 to 49) 1.23
## 1926 34 46 1.43 7 Week 7 (study day 43 to 49) 1.23
## 1927 34 47 1.43 7 Week 7 (study day 43 to 49) 1.23
## 1928 34 48 1.43 7 Week 7 (study day 43 to 49) 1.23
## 1929 34 49 0 7 Week 7 (study day 43 to 49) 1.23
## 1930 34 50 0.765 8 Week 8 (study day 50 to 56) 0.756
## 1931 34 51 0.765 8 Week 8 (study day 50 to 56) 0.756
## 1932 34 52 0.765 8 Week 8 (study day 50 to 56) 0.756
## 1933 34 53 0.749 8 Week 8 (study day 50 to 56) 0.756
## 1934 34 54 0.749 8 Week 8 (study day 50 to 56) 0.756
## 1935 34 55 0.749 8 Week 8 (study day 50 to 56) 0.756
## 1936 34 56 0.749 8 Week 8 (study day 50 to 56) 0.756
## 1937 35 0 1.44 0 Baseline 1.44
## 1938 35 1 3.25 1 Week 1 (study day 1 to 7) 3.26
## 1939 35 2 3.25 1 Week 1 (study day 1 to 7) 3.26
## 1940 35 3 3.26 1 Week 1 (study day 1 to 7) 3.26
## 1941 35 4 3.26 1 Week 1 (study day 1 to 7) 3.26
## 1942 35 5 3.26 1 Week 1 (study day 1 to 7) 3.26
## 1943 35 6 3.26 1 Week 1 (study day 1 to 7) 3.26
## 1944 35 7 3.26 1 Week 1 (study day 1 to 7) 3.26
## 1945 35 8 3.28 2 Week 2 (study day 8 to 14) 3.09
## 1946 35 9 3.28 2 Week 2 (study day 8 to 14) 3.09
## 1947 35 10 3.28 2 Week 2 (study day 8 to 14) 3.09
## 1948 35 11 3.28 2 Week 2 (study day 8 to 14) 3.09
## 1949 35 12 3.28 2 Week 2 (study day 8 to 14) 3.09
## 1950 35 13 3.28 2 Week 2 (study day 8 to 14) 3.09
## 1951 35 14 1.95 2 Week 2 (study day 8 to 14) 3.09
## 1952 35 15 1.95 3 Week 3 (study day 15 to 21) 1.83
## 1953 35 16 1.95 3 Week 3 (study day 15 to 21) 1.83
## 1954 35 17 1.78 3 Week 3 (study day 15 to 21) 1.83
## 1955 35 18 1.78 3 Week 3 (study day 15 to 21) 1.83
## 1956 35 19 1.78 3 Week 3 (study day 15 to 21) 1.83
## 1957 35 20 1.78 3 Week 3 (study day 15 to 21) 1.83
## 1958 35 21 1.78 3 Week 3 (study day 15 to 21) 1.83
## 1959 35 22 1.78 4 Week 4 (study day 22 to 28) 1.61
## 1960 35 23 1.78 4 Week 4 (study day 22 to 28) 1.61
## 1961 35 24 1.56 4 Week 4 (study day 22 to 28) 1.61
## 1962 35 25 1.56 4 Week 4 (study day 22 to 28) 1.61
## 1963 35 26 1.56 4 Week 4 (study day 22 to 28) 1.61
## 1964 35 27 1.53 4 Week 4 (study day 22 to 28) 1.61
## 1965 35 28 1.53 4 Week 4 (study day 22 to 28) 1.61
## 1966 35 29 1.53 5 Week 5 (study day 29 to 35) 1.43
## 1967 35 30 1.53 5 Week 5 (study day 29 to 35) 1.43
## 1968 35 31 1.53 5 Week 5 (study day 29 to 35) 1.43
## 1969 35 32 1.46 5 Week 5 (study day 29 to 35) 1.43
## 1970 35 33 1.46 5 Week 5 (study day 29 to 35) 1.43
## 1971 35 34 1.26 5 Week 5 (study day 29 to 35) 1.43
## 1972 35 35 1.26 5 Week 5 (study day 29 to 35) 1.43
## 1973 35 36 1.26 6 Week 6 (study day 36 to 42) 1.26
## 1974 35 37 1.26 6 Week 6 (study day 36 to 42) 1.26
## 1975 35 38 1.26 6 Week 6 (study day 36 to 42) 1.26
## 1976 35 39 1.26 6 Week 6 (study day 36 to 42) 1.26
## 1977 35 40 1.26 6 Week 6 (study day 36 to 42) 1.26
## 1978 35 41 1.26 6 Week 6 (study day 36 to 42) 1.26
## 1979 35 42 1.26 6 Week 6 (study day 36 to 42) 1.26
## 1980 35 43 1.26 7 Week 7 (study day 43 to 49) 1.17
## 1981 35 44 1.26 7 Week 7 (study day 43 to 49) 1.17
## 1982 35 45 1.26 7 Week 7 (study day 43 to 49) 1.17
## 1983 35 46 1.26 7 Week 7 (study day 43 to 49) 1.17
## 1984 35 47 1.2 7 Week 7 (study day 43 to 49) 1.17
## 1985 35 48 1 7 Week 7 (study day 43 to 49) 1.17
## 1986 35 49 1 7 Week 7 (study day 43 to 49) 1.17
## 1987 35 50 1 8 Week 8 (study day 50 to 56) 1
## 1988 35 51 1 8 Week 8 (study day 50 to 56) 1
## 1989 35 52 1 8 Week 8 (study day 50 to 56) 1
## 1990 35 53 1 8 Week 8 (study day 50 to 56) 1
## 1991 35 54 1 8 Week 8 (study day 50 to 56) 1
## 1992 35 55 1 8 Week 8 (study day 50 to 56) 1
## 1993 35 56 1 8 Week 8 (study day 50 to 56) 1
## 1994 36 0 27.3 0 Baseline 27.3
## 1995 36 1 27.8 1 Week 1 (study day 1 to 7) 5.43
## 1996 36 2 1.78 1 Week 1 (study day 1 to 7) 5.43
## 1997 36 3 1.78 1 Week 1 (study day 1 to 7) 5.43
## 1998 36 4 1.78 1 Week 1 (study day 1 to 7) 5.43
## 1999 36 5 1.78 1 Week 1 (study day 1 to 7) 5.43
## 2000 36 6 1.78 1 Week 1 (study day 1 to 7) 5.43
## 2001 36 7 1.33 1 Week 1 (study day 1 to 7) 5.43
## 2002 36 8 1.33 2 Week 2 (study day 8 to 14) 1.14
## 2003 36 9 1.33 2 Week 2 (study day 8 to 14) 1.14
## 2004 36 10 1.33 2 Week 2 (study day 8 to 14) 1.14
## 2005 36 11 1.33 2 Week 2 (study day 8 to 14) 1.14
## 2006 36 12 0.889 2 Week 2 (study day 8 to 14) 1.14
## 2007 36 13 0.889 2 Week 2 (study day 8 to 14) 1.14
## 2008 36 14 0.889 2 Week 2 (study day 8 to 14) 1.14
## 2009 36 15 0.889 3 Week 3 (study day 15 to 21) 0.889
## 2010 36 16 0.889 3 Week 3 (study day 15 to 21) 0.889
## 2011 36 17 0.889 3 Week 3 (study day 15 to 21) 0.889
## 2012 36 18 0.889 3 Week 3 (study day 15 to 21) 0.889
## 2013 36 19 0.889 3 Week 3 (study day 15 to 21) 0.889
## 2014 36 20 0.889 3 Week 3 (study day 15 to 21) 0.889
## 2015 36 21 0.889 3 Week 3 (study day 15 to 21) 0.889
## 2016 36 22 0.889 4 Week 4 (study day 22 to 28) 0.593
## 2017 36 23 0.889 4 Week 4 (study day 22 to 28) 0.593
## 2018 36 24 0 4 Week 4 (study day 22 to 28) 0.593
## 2019 37 0 0.889 0 Baseline 0.889
## 2020 37 1 0.889 1 Week 1 (study day 1 to 7) 0.741
## 2021 37 2 0.889 1 Week 1 (study day 1 to 7) 0.741
## 2022 37 3 0.889 1 Week 1 (study day 1 to 7) 0.741
## 2023 37 4 0.741 1 Week 1 (study day 1 to 7) 0.741
## 2024 37 5 0.741 1 Week 1 (study day 1 to 7) 0.741
## 2025 37 6 0.741 1 Week 1 (study day 1 to 7) 0.741
## 2026 37 7 0.741 1 Week 1 (study day 1 to 7) 0.741
## 2027 37 8 0.741 2 Week 2 (study day 8 to 14) 0.750
## 2028 37 9 0.753 2 Week 2 (study day 8 to 14) 0.750
## 2029 37 10 0.753 2 Week 2 (study day 8 to 14) 0.750
## 2030 37 11 0.753 2 Week 2 (study day 8 to 14) 0.750
## 2031 37 12 0.751 2 Week 2 (study day 8 to 14) 0.750
## 2032 37 13 0.751 2 Week 2 (study day 8 to 14) 0.750
## 2033 37 14 0.751 2 Week 2 (study day 8 to 14) 0.750
## 2034 37 15 0.752 3 Week 3 (study day 15 to 21) 0.751
## 2035 37 16 0.752 3 Week 3 (study day 15 to 21) 0.751
## 2036 37 17 0.752 3 Week 3 (study day 15 to 21) 0.751
## 2037 37 18 0.752 3 Week 3 (study day 15 to 21) 0.751
## 2038 37 19 0.751 3 Week 3 (study day 15 to 21) 0.751
## 2039 37 20 0.751 3 Week 3 (study day 15 to 21) 0.751
## 2040 37 21 0.751 3 Week 3 (study day 15 to 21) 0.751
## 2041 37 22 0.751 4 Week 4 (study day 22 to 28) 0.751
## 2042 37 23 0.751 4 Week 4 (study day 22 to 28) 0.751
## 2043 37 24 1.35 4 Week 4 (study day 22 to 28) 0.751
## 2044 37 25 0.601 4 Week 4 (study day 22 to 28) 0.751
## 2045 37 26 0.601 4 Week 4 (study day 22 to 28) 0.751
## 2046 37 27 0.601 4 Week 4 (study day 22 to 28) 0.751
## 2047 37 28 0.601 4 Week 4 (study day 22 to 28) 0.751
## 2048 37 29 0.601 5 Week 5 (study day 29 to 35) 0.495
## 2049 37 30 0.602 5 Week 5 (study day 29 to 35) 0.495
## 2050 37 31 0.452 5 Week 5 (study day 29 to 35) 0.495
## 2051 37 32 0.452 5 Week 5 (study day 29 to 35) 0.495
## 2052 37 33 0.452 5 Week 5 (study day 29 to 35) 0.495
## 2053 37 34 0.452 5 Week 5 (study day 29 to 35) 0.495
## 2054 37 35 0.452 5 Week 5 (study day 29 to 35) 0.495
## 2055 37 36 0.452 6 Week 6 (study day 36 to 42) 0.403
## 2056 37 37 0.452 6 Week 6 (study day 36 to 42) 0.403
## 2057 37 38 0.452 6 Week 6 (study day 36 to 42) 0.403
## 2058 37 39 0.377 6 Week 6 (study day 36 to 42) 0.403
## 2059 37 40 0.377 6 Week 6 (study day 36 to 42) 0.403
## 2060 37 41 0.355 6 Week 6 (study day 36 to 42) 0.403
## 2061 37 42 0.355 6 Week 6 (study day 36 to 42) 0.403
## 2062 37 43 0.355 7 Week 7 (study day 43 to 49) 0.345
## 2063 37 44 0.355 7 Week 7 (study day 43 to 49) 0.345
## 2064 37 45 0.355 7 Week 7 (study day 43 to 49) 0.345
## 2065 37 46 0.355 7 Week 7 (study day 43 to 49) 0.345
## 2066 37 47 0.355 7 Week 7 (study day 43 to 49) 0.345
## 2067 37 48 0.355 7 Week 7 (study day 43 to 49) 0.345
## 2068 37 49 0.284 7 Week 7 (study day 43 to 49) 0.345
## 2069 37 50 0.284 8 Week 8 (study day 50 to 56) 0.283
## 2070 37 51 0.284 8 Week 8 (study day 50 to 56) 0.283
## 2071 37 52 0.284 8 Week 8 (study day 50 to 56) 0.283
## 2072 37 53 0.284 8 Week 8 (study day 50 to 56) 0.283
## 2073 37 54 0.284 8 Week 8 (study day 50 to 56) 0.283
## 2074 37 55 0.282 8 Week 8 (study day 50 to 56) 0.283
## 2075 37 56 0.282 8 Week 8 (study day 50 to 56) 0.283
## 2076 38 0 2.46 0 Baseline 2.46
## 2077 38 1 2.46 1 Week 1 (study day 1 to 7) 2.48
## 2078 38 2 2.46 1 Week 1 (study day 1 to 7) 2.48
## 2079 38 3 2.46 1 Week 1 (study day 1 to 7) 2.48
## 2080 38 4 2.46 1 Week 1 (study day 1 to 7) 2.48
## 2081 38 5 2.46 1 Week 1 (study day 1 to 7) 2.48
## 2082 38 6 2.53 1 Week 1 (study day 1 to 7) 2.48
## 2083 38 7 2.53 1 Week 1 (study day 1 to 7) 2.48
## 2084 38 8 2.53 2 Week 2 (study day 8 to 14) 2.52
## 2085 38 9 2.54 2 Week 2 (study day 8 to 14) 2.52
## 2086 38 10 2.54 2 Week 2 (study day 8 to 14) 2.52
## 2087 38 11 2.54 2 Week 2 (study day 8 to 14) 2.52
## 2088 38 12 2.5 2 Week 2 (study day 8 to 14) 2.52
## 2089 38 13 2.5 2 Week 2 (study day 8 to 14) 2.52
## 2090 38 14 2.5 2 Week 2 (study day 8 to 14) 2.52
## 2091 38 15 2.47 3 Week 3 (study day 15 to 21) 2.48
## 2092 38 16 2.47 3 Week 3 (study day 15 to 21) 2.48
## 2093 38 17 2.47 3 Week 3 (study day 15 to 21) 2.48
## 2094 38 18 2.48 3 Week 3 (study day 15 to 21) 2.48
## 2095 38 19 2.48 3 Week 3 (study day 15 to 21) 2.48
## 2096 38 20 2.48 3 Week 3 (study day 15 to 21) 2.48
## 2097 38 21 2.48 3 Week 3 (study day 15 to 21) 2.48
## 2098 38 22 2.31 4 Week 4 (study day 22 to 28) 2.35
## 2099 38 23 2.31 4 Week 4 (study day 22 to 28) 2.35
## 2100 38 24 2.31 4 Week 4 (study day 22 to 28) 2.35
## 2101 38 25 2.38 4 Week 4 (study day 22 to 28) 2.35
## 2102 38 26 2.38 4 Week 4 (study day 22 to 28) 2.35
## 2103 38 27 2.38 4 Week 4 (study day 22 to 28) 2.35
## 2104 38 28 2.38 4 Week 4 (study day 22 to 28) 2.35
## 2105 38 29 2.42 5 Week 5 (study day 29 to 35) 2.44
## 2106 38 30 2.42 5 Week 5 (study day 29 to 35) 2.44
## 2107 38 31 2.42 5 Week 5 (study day 29 to 35) 2.44
## 2108 38 32 2.45 5 Week 5 (study day 29 to 35) 2.44
## 2109 38 33 2.45 5 Week 5 (study day 29 to 35) 2.44
## 2110 38 34 2.45 5 Week 5 (study day 29 to 35) 2.44
## 2111 38 35 2.45 5 Week 5 (study day 29 to 35) 2.44
## 2112 38 36 2.36 6 Week 6 (study day 36 to 42) 2.39
## 2113 38 37 2.36 6 Week 6 (study day 36 to 42) 2.39
## 2114 38 38 2.36 6 Week 6 (study day 36 to 42) 2.39
## 2115 38 39 2.41 6 Week 6 (study day 36 to 42) 2.39
## 2116 38 40 2.41 6 Week 6 (study day 36 to 42) 2.39
## 2117 38 41 2.41 6 Week 6 (study day 36 to 42) 2.39
## 2118 38 42 2.41 6 Week 6 (study day 36 to 42) 2.39
## 2119 38 43 2.39 7 Week 7 (study day 43 to 49) 2.43
## 2120 38 44 2.39 7 Week 7 (study day 43 to 49) 2.43
## 2121 38 45 2.39 7 Week 7 (study day 43 to 49) 2.43
## 2122 38 46 2.45 7 Week 7 (study day 43 to 49) 2.43
## 2123 38 47 2.45 7 Week 7 (study day 43 to 49) 2.43
## 2124 38 48 2.45 7 Week 7 (study day 43 to 49) 2.43
## 2125 38 49 2.45 7 Week 7 (study day 43 to 49) 2.43
## 2126 38 50 2.41 8 Week 8 (study day 50 to 56) 2.43
## 2127 38 51 2.41 8 Week 8 (study day 50 to 56) 2.43
## 2128 38 52 2.41 8 Week 8 (study day 50 to 56) 2.43
## 2129 38 53 2.45 8 Week 8 (study day 50 to 56) 2.43
## 2130 38 54 2.45 8 Week 8 (study day 50 to 56) 2.43
## 2131 38 55 2.45 8 Week 8 (study day 50 to 56) 2.43
## 2132 38 56 2.45 8 Week 8 (study day 50 to 56) 2.43
## 2133 39 0 2.46 0 Baseline 2.46
## 2134 39 1 2.50 1 Week 1 (study day 1 to 7) 1.60
## 2135 39 2 2.50 1 Week 1 (study day 1 to 7) 1.60
## 2136 39 3 2.49 1 Week 1 (study day 1 to 7) 1.60
## 2137 39 4 1.87 1 Week 1 (study day 1 to 7) 1.60
## 2138 39 5 1.87 1 Week 1 (study day 1 to 7) 1.60
## 2139 39 6 0 1 Week 1 (study day 1 to 7) 1.60
## 2140 39 7 0 1 Week 1 (study day 1 to 7) 1.60
## 2141 39 8 0 2 Week 2 (study day 8 to 14) 0
## 2142 39 9 0 2 Week 2 (study day 8 to 14) 0
## 2143 39 10 0 2 Week 2 (study day 8 to 14) 0
## 2144 39 11 0 2 Week 2 (study day 8 to 14) 0
## 2145 39 12 0 2 Week 2 (study day 8 to 14) 0
## 2146 39 13 0 2 Week 2 (study day 8 to 14) 0
## 2147 39 14 0 2 Week 2 (study day 8 to 14) 0
## 2148 39 15 0 3 Week 3 (study day 15 to 21) 0
## 2149 39 16 0 3 Week 3 (study day 15 to 21) 0
## 2150 39 17 0 3 Week 3 (study day 15 to 21) 0
## 2151 39 18 0 3 Week 3 (study day 15 to 21) 0
## 2152 39 19 0 3 Week 3 (study day 15 to 21) 0
## 2153 39 20 0 3 Week 3 (study day 15 to 21) 0
## 2154 39 21 0 3 Week 3 (study day 15 to 21) 0
## 2155 39 22 0 4 Week 4 (study day 22 to 28) 0
## 2156 39 23 0 4 Week 4 (study day 22 to 28) 0
## 2157 39 24 0 4 Week 4 (study day 22 to 28) 0
## 2158 39 25 0 4 Week 4 (study day 22 to 28) 0
## 2159 39 26 0 4 Week 4 (study day 22 to 28) 0
## 2160 39 27 0 4 Week 4 (study day 22 to 28) 0
## 2161 39 28 0 4 Week 4 (study day 22 to 28) 0
## 2162 39 29 0 5 Week 5 (study day 29 to 35) 0
## 2163 39 30 0 5 Week 5 (study day 29 to 35) 0
## 2164 39 31 0 5 Week 5 (study day 29 to 35) 0
## 2165 39 32 0 5 Week 5 (study day 29 to 35) 0
## 2166 39 33 0 5 Week 5 (study day 29 to 35) 0
## 2167 39 34 0 5 Week 5 (study day 29 to 35) 0
## 2168 39 35 0 5 Week 5 (study day 29 to 35) 0
## 2169 39 36 0 6 Week 6 (study day 36 to 42) 0
## 2170 39 37 0 6 Week 6 (study day 36 to 42) 0
## 2171 39 38 0 6 Week 6 (study day 36 to 42) 0
## 2172 39 39 0 6 Week 6 (study day 36 to 42) 0
## 2173 39 40 0 6 Week 6 (study day 36 to 42) 0
## 2174 39 41 0 6 Week 6 (study day 36 to 42) 0
## 2175 39 42 0 6 Week 6 (study day 36 to 42) 0
## 2176 39 43 0 7 Week 7 (study day 43 to 49) 0
## 2177 39 44 0 7 Week 7 (study day 43 to 49) 0
## 2178 39 45 0 7 Week 7 (study day 43 to 49) 0
## 2179 39 46 0 7 Week 7 (study day 43 to 49) 0
## 2180 39 47 0 7 Week 7 (study day 43 to 49) 0
## 2181 39 48 0 7 Week 7 (study day 43 to 49) 0
## 2182 39 49 0 7 Week 7 (study day 43 to 49) 0
## 2183 39 50 0 8 Week 8 (study day 50 to 56) 0
## 2184 39 51 0 8 Week 8 (study day 50 to 56) 0
## 2185 39 52 0 8 Week 8 (study day 50 to 56) 0
## 2186 39 53 0 8 Week 8 (study day 50 to 56) 0
## 2187 39 54 0 8 Week 8 (study day 50 to 56) 0
## 2188 39 55 0 8 Week 8 (study day 50 to 56) 0
## 2189 39 56 0 8 Week 8 (study day 50 to 56) 0
3. What do the individual patient data look like?
The purpose of this plot is getting an initial “feel” for trends and
variability in the raw data. With only 39 subjects a facet-plot showing
dose vs. time for each individual was feasible. Facet were arranged from
left to right and top to bottom in order of decreasing strength of
correlation (values of the Somer’s rank correlation coefficient are
shown in the next plot). Because the GC pulses represented extreme
outliers, I used log scale to visualise trends, namely in the lower
value range. Horizontal lines at 0.2, 0.5 and 1mg/kg/day define the
three GC thresholds mentioned in the challenge. Additionally, doses
>10mg/kg/day define GC pulses.
## - Chunk 1, requires WW_GCdose and R libraries (chunk libraries_and_data)
## - Glucocorticoid dose vs. time in individual subjects
WW_GCdose_somersD <-
WW_GCdose %>%
mutate(
pulses = ifelse(
AVAL1 < 10, 0, 1
)
) %>%
split (.$SUBJID) %>%
# Compute correlation for time after the start of treatment (d0: baseline)
lapply(function(df) filter(df, !ASTDY == 0) ) %>%
lapply( function(x)
c(
pulses = sum(x$pulses),
SomersDelta(
x = x$ASTDY,
y = x$AVAL1,
direction = "column",
conf.level = 0.95
)
)
) %>%
bind_rows(.id = "SUBJID") %>%
arrange(somers) %>%
mutate(SUBJID = factor (SUBJID, levels = unique(SUBJID)))
WW_GCdose <-
WW_GCdose %>%
mutate(
SUBJID = factor(
SUBJID,
levels(WW_GCdose_somersD$SUBJID)
)
) %>%
# Sorts subjects by trend for lowering GC dose over time, in descending order
arrange(SUBJID) %>%
group_by(SUBJID) %>%
mutate(
censored = ifelse(
which.max(ASTDY) < 56,
which.max(ASTDY), NA
)
) %>%
ungroup
WW_GCdose %>%
ggplot(
aes(x= ASTDY, y = AVAL1)
) +
geom_line() +
geom_hline(
yintercept = c(1, 0.5, 0.2, 10),
colour = "darkgrey",
linetype = "dashed"
) +
geom_vline(
aes(
xintercept = censored,
linetype = "Censored\nbefore day 56"
),
color = "red",
linewidth = 0.01
) +
scale_y_log10(
breaks = c(0, 0.2, 0.5, 1, 10)
) +
labs(
title = "Glucocorticoid dose versus time in individual subjects",
subtitle = "Subject ID",
caption = "Subjects sorted by rank correlation between glucocorticoid dose and time (Somers' D)\n
Dashed lines: dose thresholds 0.2, 0.5, 1.0, and 10mg/kg/d",
linetype = NULL) +
xlab("Time (d)") +
ylab("Glucocorticoid dose, log10 (mg/kg/d)") +
facet_wrap(
facets = "SUBJID",
nrow = 3
) +
theme_minimal() +
theme(
plot.title = element_text(
hjust = 0.5,
vjust = 3
),
plot.subtitle = element_text(
hjust = 0.5,
vjust = -3,
size = 9,
color = "blue"
),
plot.caption = element_text(
size = 9,
hjust = 0.5
),
strip.text.x = element_text(
color = "blue"
),
panel.grid.minor = element_blank()
)
High inter-individual variation can be observed, regarding baseline
values (day 0), trends for GC use vs. time, and the times when various
threshold levels were crossed.
Although generally the frequency of GC pulses decreased with treatment
time, they were still given at mid- to late stage in a few subjects (19,
29, 23).
Red vertical lines mark censored data in two individuals. This is useful
information for the analyses, i.e. sample averages at different time
points should not be calculated by dividing by sample size at baseline
(N = 39), but rather by the actual sample size at each time point.
4. Did GC use change significantly in the follow-up period after initiation of the experimental treatment?
Somers’ D is a non-parametric measure of correlation related to
Goodman-Kruskal’s Gamma and Kendall’s Tau-b. In contrast to the latter,
the asymmetric Somers’ D coefficient is appropriate where of the
variables being dependent on the other, as in this case 3.
## - Chunk 2, requires WW_GCdose_somersD (chunk 1):
## - Correlation between GC dose and time of follow-up in individual subjects, with varying total length of pulse therapy
WW_GCdose_somersD %>%
rbind(
.,
select(., !c(SUBJID, pulses)) %>%
apply(., 2, median) %>% t %>%
data.frame(SUBJID = "\nAll \n(median)", pulses = NA)
) %>%
ggplot(
aes(
y = SUBJID,
x = somers,
color = pulses
)
) +
geom_point(
size = 2.5
) +
geom_errorbarh(
aes(
xmin = lwr.ci,
xmax = upr.ci
)
) +
scale_y_discrete(limits=rev) +
scale_color_gradient(
low = "#4aa2e6",
high = "#c7505c",
na.value = "black",
name = "Glucocorticoid \npulses: \ntotal days on \n>= 10mg/kg/d"
) +
ylab("Subject ID") +
xlab("Somers' D") +
labs(
title = "Correlation between glucocorticoid dose and interventional time in individual subjects,\nwith varying total length of pulse therapy",
caption = "Asymetric Somers' D with 95% CIs, dependent variable is glucocorticoid dose\n56d follow-up, except for subjects #11 (55d) and #36 (25d)") +
theme_minimal() +
theme(
plot.title = element_text(
hjust = 0.5,
vjust = 3
),
plot.caption = element_text(
hjust = 0.5,
vjust = -3
),
legend.title = element_text(size = 9)
)
The correlation coefficients for GC dose vs. time, including their
95% CIs, were negative for all subjects but one. The median Somers’ D
across all patients was -0.817 (95% CI: -0.898 - -0.722). Strength of
correlation seemed not associated with the total length of time patients
received GC pulse therapy, probably because the frequency of the
high-dose outliers/pulses decreased over the treatment period.
5. What shifts between clinically important threshold levels occured at the individual subject level, and how did the proportions of subjects recieving doses above different thresholds change over time?
The upper of the two panels is a “spaghetti plot”. This format offers
a more compact way to visualise dose changes over time than the faceted
line plots above, although at the expense of time-dependent resolution
(qualitative changes) and/or clarity (colour instead of height).
Subjects on the y-axis are sorted by dose level, consecutively from day
1 to day 56 of the treatment (ignoring baseline values at day 0). This
makes the spaghetti plot more similar in appearance and comparable to
the stacked area plot in the lower panel, showing changes in the
proportion of patients with dose ranges between different threshold
levels.
## - Chunk 3, requires WW_GCdose (chunk 1):
## - Fraction of patients receiving glucocorticoid doses above clinical thresholds versus time at baseline (day 0) and over the course of the investigational treatment
## Define thresholds, threshold colors, and threshold data
# Define clinically relevant glucocorticoid thresholds
GC_threshold <- c(0.2, 0.5, 1, 10)
# Define color palette distinguishing thresholds in the plot
threshold_palette <-
setNames(
c("darkblue", "#4aa2e6", "#8ccfa8", "#e8bb61", "#c7505c"),
c(0, GC_threshold)
)
# Create a nested dataframe with threshold values and thresholded GC doses vs. time
threshold_GCdata <-
tibble(
threshold_value = GC_threshold
) %>%
mutate(GCdata = map(threshold_value, function(thresh) {
WW_GCdose %>%
select(SUBJID, ASTDY, AVAL1, censored) %>%
pivot_wider(
names_from = "ASTDY",
values_from = "AVAL1"
) %>%
mutate(
across(
!c(SUBJID, censored),
~ ifelse(.x >= thresh, 1, 0)
)
)
}))
## Create plot for showing dose thresholds for individual patients vs. time
# Function for summing tibbles in a nested dataframe, element-wise
sum_tibbles <- function(df, nested_col_name, ID_col_name) {
# Extract list of tibbles
tibble_list <- df[[nested_col_name]]
# Get SUBJID column from first tibble
id_col <- tibble_list[[1]] %>% select(all_of(ID_col_name))
tibble_list %>%
# For each tibble, drop the SUBJID column (added back later)
map(~select(.x, -all_of(ID_col_name))) %>%
# Sum all tibbles together element-wise
reduce(`+`) %>%
# Bind the SUBJID column back
bind_cols(id_col, .)
}
# Create plot
dose_labels <- threshold_GCdata$threshold_value %>%
{ c(
paste ("0 -", .[1]),
paste( .[-length(.)], "-", .[-1]),
paste ("> ", .[length(.)]),
"NA"
) }
p1 <- threshold_GCdata %>%
sum_tibbles(., "GCdata", "SUBJID") %>%
# Join with WW_GCdose_somersD is only required when showing Somers' D in the plot
left_join(WW_GCdose_somersD %>% select(SUBJID, somers), .) %>%
# Sort so that patients dosed at the same threshold levels tend to group together, helping to compare this plot with the plot of patient fractions, p2)
arrange(
desc(
across(!c(SUBJID, somers, censored, `0`) )
)
) %>%
mutate(
SUBJID = factor(
SUBJID,
levels = unique (SUBJID) %>% rev
)
) %>%
pivot_longer(
cols = !c(SUBJID, somers, censored),
names_to = "Time",
values_to = "Threshold_level"
) %>%
mutate(
Time = as.numeric(Time),
Threshold_level = factor(Threshold_level),
SUBJID = factor(
SUBJID, levels = rev(levels(SUBJID) )
)
) %>%
ggplot(
aes(
# Optional: Indicate strength of correlation of GC dose dependent on time (Somers' D)
# alpha = somers,
x = Time,
y = SUBJID,
colour = Threshold_level,
group = SUBJID
)
) +
geom_line(lwd = 3) +
scale_x_continuous(
breaks = seq(0, 50, 10),
expand = c(0,0)) +
scale_color_discrete(
type = as.character(threshold_palette),
na.value = "yellow",
labels = dose_labels
) +
# Scale alpha is only required when showing Somers' D (stronger colour for stronger negative correlation)
scale_alpha(
range = c(1, -0.3)
) +
labs(
x = "Time(d)",
y = "Subject ID",
color = "Dose level \n(mg/kg/d)",
alpha = "Somers' D") +
theme_light() +
theme(
axis.text = element_text(size = 11),
legend.title = element_text(size = 11),
legend.text = element_text(size = 11),
panel.grid = element_blank()
)
# Notes
# Use of all_of() in function sum_tibbles: without it R treats -ID_col_name as looking for a column literally named "ID_col_name" rather than using the value of the variable. If the column name contains special characters or starts with a number, using all_of() ensures it's properly handled
# Group = SUBJID in ggplot is necessary because Threshold_level is an ordinal/categorical variable and this would introduce gaps between the colors of each bar
## Create plot for fractions of patients with doses above threshold levels vs. time
# Calculate fraction of patients above various thresholds at each time point
patients_above_threshold <-
threshold_GCdata %>%
mutate(
summary_data = map(GCdata, function(df) {
df %>%
select(-c(SUBJID, censored)) %>%
summarize(across(everything(),
~ sum(.x, na.rm = TRUE) / sum(!is.na(.x)))) %>%
pivot_longer(
cols = everything(),
names_to = "Time",
values_to = "Fraction"
) %>%
mutate(Time = as.numeric(Time) )
} )
) %>%
select(threshold_value, summary_data) %>%
unnest(summary_data) %>%
mutate(Threshold = factor(threshold_value))
# Create plot
p2 <- patients_above_threshold %>%
ggplot(
aes(
x = Time,
y = Fraction,
fill = Threshold
)
) +
# Add an area for the remaining values, less than the lowest threshold in the input dataframe
geom_area(aes(y = 1, fill = "0"), alpha = 0.7) +
# Plot the other areas on top
geom_area(
position = 'identity'
) +
scale_y_continuous(
labels = scales::percent
) +
scale_fill_manual(
values =
threshold_palette
) +
xlab("Time (d)") +
ylab("Fraction of patients (%)") +
theme_minimal() +
theme(
plot.title = element_text(hjust = 0.5, vjust = 2),
plot.subtitle = element_text(hjust = 0.5),
plot.caption = element_text(size = 10, hjust = 0.5),
axis.text = element_text(size = 11),
legend.position = "none",
panel.grid = element_line(
linetype = 3,
linewidth = 1),
panel.ontop = T
) +
coord_cartesian(ylim = c(-0.01, 1.01), expand = FALSE)
p1 + p2 +
plot_layout(
design = "A
A
B"
) +
plot_annotation(
title = "Patients receiving glucocorticoid doses above clinical thresholds versus time \nat baseline (day 0) and over the course of the investigational treatment",
theme = theme(
plot.title = element_text(
size = 14,
hjust = 0.5
)
)
) 
As an optional feature, the correlation of dose vs. time in
individual subjects can be shown by increasing the transparency of the
coloured bars with decreasing negative correlation strength. This could
be useful for focussing on subjects where changes from higher to lower
thresholds are part of a strong general trend for decreasing dose with
treatment time. However, finding a range for the transparency scale that
provided satisfactory visual discrimination was not easy with this set
of values.
6. How much, on average, did the investigational treatment reduce GC use below clinically relevant thresholds?
Instead of looking at changes in patient numbers, this figure tries
to quantify the days that an average patient might (no longer) need GC
doses above certain thresholds. This transformation smoothes the effect
of extreme changes, i.e. the GC pulses, while preserving their effect on
the variability of the sample. The x-axis represents the accumulated
time since start of the investigational treatment, the y-axis the
average fraction of days that patients were dosed above individual
threshold levels. Confidence intervals illustrate the variability of the
patient data, and that the apparent decline in over-the-threshold dosing
might not be significant except for the 10mg/kg/day level (GC
pulses).
The visualisation could be useful for assessing whether the benefits of
treatment are increasing with time, and when the change will become
significant for the average patient.
## - Chunk 4, requires threshold_GCdata, threshold_palette (chunk 3):
## - Fraction of interventional time during which patients received glucocorticoid doses above clinical thresholds
# Calculate cumulative statistics by iterating in parallel over CG threshold values and thresholded dataframes
days_above_threshold <- threshold_GCdata %>%
mutate(
cumulative_data_stats = map2(GCdata, threshold_value, function(df, thresh_value) {
# Extract only the numeric columns for processing
followUp_GCdata <- df %>% select(!c(SUBJID, censored, "0"))
# Get numeric time points for proper ordering later
time_points <- as.numeric(names(followUp_GCdata))
# Calculate cumulative ratios, keep NA for censored time points
time_avg <- df %>%
select(!c(SUBJID, censored, "0")) %>%
apply(1, function(x) cumsum(x) / time_points) %>%
t()
# Calculate statistics for each time point
map_df(seq_along(time_points), function(i) {
tibble(
Threshold = thresh_value,
Time = time_points[i],
n_valid = sum(!is.na(time_avg[, i])),
Mean = mean(time_avg[, i], na.rm = TRUE),
SD = sd(time_avg[, i], na.rm = TRUE)
)
})
})
) %>%
select(cumulative_data_stats) %>%
unnest(cumulative_data_stats) %>%
mutate(
Threshold = factor(Threshold),
SE = SD / sqrt(n_valid),
CI.lwr = Mean - qt(0.975, n_valid - 1) * SE,
CI.upr = Mean + qt(0.975, n_valid - 1) * SE
)
# Create plot
days_above_threshold %>%
ggplot(
aes(
x = Time,
y = Mean,
color = Threshold
)
) +
geom_ribbon(
aes(
ymin = CI.lwr,
ymax = CI.upr,
fill = Threshold
),
show.legend = FALSE,
alpha = 0.2,
linetype = 3,
linewidth = 0.01
) +
geom_line(
linewidth = 1.2
) +
scale_y_continuous(
labels = percent
) +
scale_color_discrete (
type = threshold_palette[-1],
labels = paste (">", threshold_GCdata$threshold_value)
) +
scale_fill_discrete (type = threshold_palette[-1]) +
labs(
title = "Fraction of interventional time\nduring which patients received glucocorticoid doses above clinical thresholds",
caption = "Mean across patients (thick coloured lines), with 95%CIs (shaded areas)",
color = "Dose level \n(mg/kg/d)"
) +
xlab("Investigational treatment interval (d)") +
ylab("Fraction of days with doses > threshold") +
theme_minimal() +
theme(
plot.title = element_text(hjust = 0.5, vjust = 5),
plot.subtitle = element_text(hjust = 0.5),
plot.caption = element_text(size = 10, hjust = 0.5, vjust = -5),
legend.title = element_text(size = 9),
plot.margin = unit(c(0.5, 0, 0.5, 0), "cm")
) +
# Display values inside the 0 - 100% range only (greater or smaller makes no sense),
# zooming in with coord_cartesian because setting limits in scale_y_continuous will cause an error if geom_ribbon values exist outside the scale range
coord_cartesian(ylim = c(-0.01, 1.01), expand = F) 
7. References
- Current treatment in macrophage activation syndrome worldwide: a systematic literature review to inform the METAPHOR project. Baldo F, Erkens RGA, Mizuta M, Rogani G, Lucioni F, Bracaglia C, Foell D, Gattorno M, Jelusic M, Anton J, Brogan P, Canna S, Chandrakasan S, Cron RQ, De Benedetti F, Grom A, Heshin-Bekenstein M, Horne A, Khubchandani R, Ozen S, Quartier P, Ravelli A, Shimizu M, Schulert G, Scott C, Sinha R, Ruperto N, Swart JF, Vastert S, Minoia F; PReS MAS/sJIA Working Party and Paediatric Rheumatology International Trial Organization. Rheumatology (Oxford). 2025 Jan 1;64(1):32-44. https://doi.org/10.1093/rheumatology/keae391
- Evidence-based diagnosis and treatment of macrophage activation syndrome in systemic juvenile idiopathic arthritis. Boom V, Anton J, Lahdenne P, Quartier P, Ravelli A, Wulffraat NM, Vastert SJ. Pediatr Rheumatol Online J. 2015 Dec 3;13:55. https://ped-rheum.biomedcentral.com/articles/10.1186/s12969-015-0055-3
- https://www.statisticshowto.com/somers-d/