NorthWest Biotherapeutics Inc (NWBO)

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NWBO DCVax-L Survival Analysis Models show significant survival benefit

Finally I have finished the Survival Model for the DCVax-L Trial.
Model Parameters:

1. First developed a spreadsheet using the entry ramp published at ASCO 2017 by Bousch MD and NWBO.

2.Assigned in a 2 to 1 ratio the experimental and Placebo groups.

3. Used the IMUC Published ITT survival curves (published at ASCO 2014) to extrapolate to the NWBO dataset. The primary assumption for this model is that the IMUC Control Survival will be essentially equal to the NWBO Control Survival Curve. This is a reasonable assumption as the entry requirements for the IMUC trial and the NWBO trial are very similar.

4 The model for the NWBO control patients data to be equivalent to the IMUC Control Data, requires 87 death events to for the NWBO control group. It was disclosed at ASCO 2017 that there were still 100 Patients alive in the entire NWBO dataset. Therefore, there would be 331-100 or 231 total death events for the entire NWBO dataset. Utilizing the derived 87 death events from the model, one then can ascertain that there would be 144 death events in the DCVax-L treatment group (ie 231-87=144).

5. Armed with this derived number of events (144) in the experimental arm, one can model the experimental arm by modeling the NWBO data using the IMUC Control arm date but limiting the number of death events to only 144.

6. One then can then compare the overall survival KM survival curves for the DCVax-L experimental group (N=221) and the Placebo group (N=110).
When one does this the results show a statistically significant (p=.029) improvement in OS favoring the treatment group with a Median OS of 19 vs 15 months and a 75 Quartile survival not yet obtained by the experimental group.

To visualize the Survival Curve click on this link.

https://dl.dropboxusercontent.com/u/11047753/NWBO%20Survival%20Curve.JPG


Summary statistics (Events):

Stratum Total observed Total failed Total censored Time steps
1 DCVAX-L 221 141 80 164
2 PLACEBO 110 87 23 79



Test of equality of the survival distribution functions (DF = 1):
COMPARISION OF GROUPS
Statistic Observed value Critical value p-value alpha
Log-rank 5.474 3.841 0.019 0.050
Wilcoxon 4.784 3.841 0.029 0.050
Tarone-Ware 5.268 3.841 0.022 0.050


NWBO CONTROL Patients DATA:
Results for 2: PLACEBO

Summary statistics (2):

Total observed Total failed Total censored
110 87 23

Mean survival time (2):

Mean survival NWBO Control time (IMUC Control Mos Fup or death expanded<107.255333333333) Standard deviation Lower bound (95%) Upper bound (95%)
33.998 3.633 26.878 41.119


Quantiles estimation (2):

Quantile Estimate Lower bound (95%) Upper bound (95%)
75% 32.000 19.667
50% 15.167 13.333 17.833
25% 10.600 10.333 12.000

Kaplan-Meier table (2): NWBO CONTROL PATIENTS

IMUC Control Mos Fup or death expanded At risk Failed Censored Proportion failed Survival rate Survival distribution function
6.666667 110 1 0 0.009 0.991 0.991
6.8 109 1 0 0.009 0.991 0.982
7.333333 108 2 0 0.019 0.981 0.964
7.833333 106 1 0 0.009 0.991 0.955
8.333333 105 3 0 0.029 0.971 0.927
8.5 102 2 0 0.020 0.980 0.909
8.533333 100 1 0 0.010 0.990 0.900
8.666667 99 2 0 0.020 0.980 0.882
9.4 97 1 0 0.010 0.990 0.873
10.13333 96 1 0 0.010 0.990 0.864
10.26667 95 3 0 0.032 0.968 0.836
10.3 92 1 0 0.011 0.989 0.827
10.33333 91 1 0 0.011 0.989 0.818
10.4 90 4 0 0.044 0.956 0.782
10.5 86 1 0 0.012 0.988 0.773
10.56667 85 1 0 0.012 0.988 0.764
10.6 84 2 0 0.024 0.976 0.745
10.7 82 1 0 0.012 0.988 0.736
10.8 81 2 0 0.025 0.975 0.718
11 79 1 0 0.013 0.987 0.709
11.33333 78 2 0 0.026 0.974 0.691
11.5 76 1 0 0.013 0.987 0.682
11.66667 75 2 0 0.027 0.973 0.664
12 73 1 0 0.014 0.986 0.655
12.33333 72 1 0 0.014 0.986 0.645
12.85 71 1 0 0.014 0.986 0.636
13.16667 70 2 0 0.029 0.971 0.618
13.25 68 1 0 0.015 0.985 0.609
13.33333 67 2 0 0.030 0.970 0.591
13.38333 65 1 0 0.015 0.985 0.582
13.43333 64 1 0 0.016 0.984 0.573
13.46667 63 1 0 0.016 0.984 0.564
13.5 62 2 0 0.032 0.968 0.545
13.75 60 1 0 0.017 0.983 0.536
14 59 2 0 0.034 0.966 0.518
15 57 2 0 0.035 0.965 0.500
15.16667 55 1 0 0.018 0.982 0.491
15.33333 54 2 0 0.037 0.963 0.473
15.5 52 1 0 0.019 0.981 0.464
15.66667 51 1 0 0.020 0.980 0.455
16.33333 50 1 0 0.020 0.980 0.445
17 49 2 0 0.041 0.959 0.427
17.41667 47 1 0 0.021 0.979 0.418
17.83333 46 2 0 0.043 0.957 0.400
18.33333 44 1 0 0.023 0.977 0.391
18.83333 43 1 0 0.023 0.977 0.382
19.08333 42 1 0 0.024 0.976 0.373
19.33333 41 2 0 0.049 0.951 0.355
19.5 39 1 0 0.026 0.974 0.345
19.66667 38 2 0 0.053 0.947 0.327
21.3 36 0 1
23.33333 35 1 0 0.029 0.971 0.318
23.36667 34 1 0 0.029 0.971 0.309
23.4 33 2 0 0.061 0.939 0.290
23.5 31 1 0 0.032 0.968 0.281
27.66667 30 1 0 0.033 0.967 0.271
32 29 7 0 0.241 0.759 0.206
34 22 0 1
105.1463 21 0 1
105.2573 20 0 1
105.3683 19 0 1
105.4793 18 0 1
105.5903 17 0 1
105.7013 16 0 1
105.8123 15 0 1
105.9233 14 0 1
106.0343 13 0 1
106.1453 12 0 1
106.2563 11 0 1
106.3673 10 0 1
106.4783 9 0 1
106.5893 8 0 1
106.7003 7 0 1
106.8113 6 0 1
106.9223 5 0 1
107.0333 4 0 1
107.1443 3 0 1
107.2553 2 0 1
107.3943 1 0 1

NWBO EXPERIMENTAL DCVaX-L Treatment ARM DATA:

Results for 1:DCVAC-L TREATMENT Experimental Group

Summary statistics (1):

Total observed Total failed Total censored
221 141 80

Mean survival time (1):

Mean survival time (IMUC Control Mos Fup or death expanded<35.6146666666648) Standard deviation Lower bound (95%) Upper bound (95%)
22.236 0.744 20.777 23.695


Quantiles estimation (1):

QuantileEstimate Lower bound (95%) Upper bound (95%)
75%
50% 18.967 15.667 23.400
25% 11.500 10.600 13.250




IMUC Control Mos Fup or death expanded At risk Failed Censored Proportion failed Survival rate Survival distribution function Standard error of the survival function Lower bound (95%) Upper bound (95%)
6.666667 221 1 0 0.005 0.995 0.995 0.005 0.987 1.000
6.8 220 1 0 0.005 0.995 0.991 0.006 0.978 1.000
7 219 1 0 0.005 0.995 0.986 0.008 0.971 1.000
7.333333 218 2 0 0.009 0.991 0.977 0.010 0.958 0.997
7.6 216 1 0 0.005 0.995 0.973 0.011 0.951 0.994
7.833333 215 1 0 0.005 0.995 0.968 0.012 0.945 0.991
8.333333 214 4 0 0.019 0.981 0.950 0.015 0.922 0.979
8.4 210 1 0 0.005 0.995 0.946 0.015 0.916 0.976
8.466667 209 1 0 0.005 0.995 0.941 0.016 0.910 0.972
8.5 208 3 0 0.014 0.986 0.928 0.017 0.893 0.962
8.533333 205 1 0 0.005 0.995 0.923 0.018 0.888 0.958
8.666667 204 3 0 0.015 0.985 0.910 0.019 0.872 0.947
9.4 201 1 0 0.005 0.995 0.905 0.020 0.866 0.944
9.733333 200 1 0 0.005 0.995 0.900 0.020 0.861 0.940
10.13333 199 1 0 0.005 0.995 0.896 0.021 0.856 0.936
10.26667 198 5 0 0.025 0.975 0.873 0.022 0.829 0.917
10.3 193 2 0 0.010 0.990 0.864 0.023 0.819 0.909
10.33333 191 2 0 0.010 0.990 0.855 0.024 0.809 0.902
10.4 189 5 0 0.026 0.974 0.833 0.025 0.783 0.882
10.46667 184 2 0 0.011 0.989 0.824 0.026 0.773 0.874
10.5 182 1 0 0.005 0.995 0.819 0.026 0.768 0.870
10.56667 181 1 0 0.006 0.994 0.814 0.026 0.763 0.866
10.6 180 3 0 0.017 0.983 0.801 0.027 0.748 0.854
10.66667 177 1 0 0.006 0.994 0.796 0.027 0.743 0.849
10.7 176 1 0 0.006 0.994 0.792 0.027 0.738 0.845
10.8 175 3 0 0.017 0.983 0.778 0.028 0.724 0.833
11 172 1 0 0.006 0.994 0.774 0.028 0.719 0.829
11.16667 171 2 0 0.012 0.988 0.765 0.029 0.709 0.821
11.33333 169 2 0 0.012 0.988 0.756 0.029 0.699 0.812
11.43333 167 1 0 0.006 0.994 0.751 0.029 0.694 0.808
11.5 166 1 0 0.006 0.994 0.747 0.029 0.689 0.804
11.66667 165 3 0 0.018 0.982 0.733 0.030 0.675 0.791
12 162 1 0 0.006 0.994 0.729 0.030 0.670 0.787
12.16667 161 1 0 0.006 0.994 0.724 0.030 0.665 0.783
12.3 160 1 0 0.006 0.994 0.719 0.030 0.660 0.779
12.33333 159 1 0 0.006 0.994 0.715 0.030 0.655 0.774
12.85 158 1 0 0.006 0.994 0.710 0.031 0.651 0.770
13 157 2 0 0.013 0.987 0.701 0.031 0.641 0.762
13.16667 155 2 0 0.013 0.987 0.692 0.031 0.631 0.753
13.25 153 1 0 0.007 0.993 0.688 0.031 0.627 0.749
13.33333 152 3 0 0.020 0.980 0.674 0.032 0.612 0.736
13.38333 149 1 0 0.007 0.993 0.670 0.032 0.608 0.732
13.4 148 1 0 0.007 0.993 0.665 0.032 0.603 0.727
13.43333 147 2 0 0.014 0.986 0.656 0.032 0.593 0.719
13.46667 145 2 0 0.014 0.986 0.647 0.032 0.584 0.710
13.5 143 3 0 0.021 0.979 0.633 0.032 0.570 0.697
13.63333 140 1 0 0.007 0.993 0.629 0.032 0.565 0.693
13.75 139 1 0 0.007 0.993 0.624 0.033 0.561 0.688
14 138 3 0 0.022 0.978 0.611 0.033 0.547 0.675
15 135 3 0 0.022 0.978 0.597 0.033 0.533 0.662
15.16667 132 1 0 0.008 0.992 0.593 0.033 0.528 0.658
15.23333 131 1 0 0.008 0.992 0.588 0.033 0.523 0.653
15.26667 130 1 0 0.008 0.992 0.584 0.033 0.519 0.649
15.33333 129 2 0 0.016 0.984 0.575 0.033 0.509 0.640
15.43333 127 1 0 0.008 0.992 0.570 0.033 0.505 0.635
15.5 126 1 0 0.008 0.992 0.566 0.033 0.500 0.631
15.66667 125 1 0 0.008 0.992 0.561 0.033 0.496 0.627
16 124 1 0 0.008 0.992 0.557 0.033 0.491 0.622
16.33333 123 1 0 0.008 0.992 0.552 0.033 0.486 0.618
17 122 3 0 0.025 0.975 0.538 0.034 0.473 0.604
17.41667 119 1 0 0.008 0.992 0.534 0.034 0.468 0.600
17.6 118 1 0 0.008 0.992 0.529 0.034 0.464 0.595
17.76667 117 1 0 0.009 0.991 0.525 0.034 0.459 0.591
17.83333 116 2 0 0.017 0.983 0.516 0.034 0.450 0.582
18.06667 114 1 0 0.009 0.991 0.511 0.034 0.445 0.577
18.33333 113 1 0 0.009 0.991 0.507 0.034 0.441 0.573
18.83333 112 1 0 0.009 0.991 0.502 0.034 0.436 0.568
18.96667 111 1 0 0.009 0.991 0.498 0.034 0.432 0.564
19.08333 110 1 0 0.009 0.991 0.493 0.034 0.427 0.559
19.33333 109 3 0 0.028 0.972 0.480 0.034 0.414 0.546
19.5 106 1 0 0.009 0.991 0.475 0.034 0.409 0.541
19.56667 105 1 0 0.010 0.990 0.471 0.034 0.405 0.536
19.6 104 1 0 0.010 0.990 0.466 0.034 0.400 0.532
19.66667 103 2 0 0.019 0.981 0.457 0.034 0.391 0.523
20.83333 101 0 1
21.6 100 1 0 0.010 0.990 0.452 0.033 0.387 0.518
23.33333 99 1 0 0.010 0.990 0.448 0.033 0.382 0.513
23.36667 98 1 0 0.010 0.990 0.443 0.033 0.378 0.509
23.4 97 3 0 0.031 0.969 0.430 0.033 0.364 0.495
23.46667 94 1 0 0.011 0.989 0.425 0.033 0.360 0.490
23.5 93 1 0 0.011 0.989 0.420 0.033 0.355 0.486
27.06767 92 0 1
27.17867 91 0 1
27.28967 90 0 1
27.40067 89 0 1
27.51167 88 0 1
27.62267 87 0 1
27.66667 86 1 0 0.012 0.988 0.416 0.033 0.350 0.481
27.73367 85 0 1
27.84467 84 0 1
27.95567 83 0 1
28.06667 82 0 1
28.17767 81 0 1
28.28867 80 0 1
28.39967 79 0 1
28.51067 78 0 1
28.62167 77 0 1
28.73267 76 0 1
28.84367 75 0 1
28.95467 74 0 1
29.06567 73 0 1
29.17667 72 0 1
29.28767 71 0 1
29.33333 70 1 0 0.014 0.986 0.410 0.033 0.344 0.475
29.39867 69 0 1
29.50967 68 0 1
29.62067 67 0 1
29.73167 66 0 1
29.84267 65 0 1
29.95367 64 0 1
30.06467 63 0 1
30.17567 62 0 1
30.28667 61 0 1
30.39767 60 0 1
30.50867 59 0 1
30.61967 58 0 1
30.66667 57 1 0 0.018 0.982 0.402 0.033 0.337 0.468
30.73067 56 0 1
30.84167 55 0 1
30.95267 54 0 1
31.06367 53 0 1
31.17467 52 0 1
31.28567 51 0 1
31.39667 50 0 1
31.50767 49 0 1
31.61867 48 0 1
31.72967 47 0 1
31.84067 46 0 1
31.95167 45 0 1
32 44 10 0 0.227 0.773 0.311 0.036 0.240 0.382
32.06267 34 0 1
32.17367 33 0 1
32.28467 32 0 1
32.39567 31 0 1
32.50667 30 0 1
32.61767 29 0 1
32.72867 28 0 1
32.83967 27 0 1
32.95067 26 0 1
33.06167 25 0 1
33.17267 24 0 1
33.28367 23 0 1
33.39467 22 0 1
33.50567 21 0 1
33.61667 20 0 1
33.72767 19 0 1
33.83867 18 0 1
33.94967 17 0 1
34.06067 16 0 1
34.17167 15 0 1
34.28267 14 0 1
34.39367 13 0 1
34.50467 12 0 1
34.61567 11 0 1
34.72667 10 0 1
34.83767 9 0 1
34.94867 8 0 1
35.05967 7 0 1
35.17067 6 0 1
35.28167 5 0 1
35.39267 4 0 1
35.50367 3 0 1
35.61467 2 0 1
35.72567 1 0 1

Discloser
I am long NWBO stock; I am a clinical Researcher