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p<0.0001
p<0.05
p<0.0001
p<0.0001
(A)
(B)
p<0.0001
p<0.05
p<0.05
p<0.01
128
512
p<0.0001
64
256
32
128
64
16
32
8
16
4
8
2
4
1
2
0.5
1
0.25
0.5
0.125
0.25
Disease type
Disease type
FIGURE 1.6
Overexpression of type I IFN-inducible genes as captured by the five gene type I IFN signature
scores in the WB and disease tissues of subjects with SLE, DM, PM, RA and SSc. Five gene type I IFN signature
scores in (A) WB and (B) disease tissues for healthy and diseased subjects [healthy subjects (N = 24); SLE (N =
262); DM (N = 44); PM (N = 33); RA (N = 89); SSc (N = 38)]. The p values for the signature scores between healthy
subjects and SLE, DM, PM, RA and SSc subjects in the WB after adjustment for gender and age are p < 0.0001, p <
0.0001, p < 0.0001, p < 0.05 and p < 0.0001, respectively. The p values for the lesional skin from SLE (N = 16) and
SSc (N = 16) subjects compared with normal healthy subjects (N = 25) is p < 0.05 for both and p < 0.0001 and p <
0.01 in muscle specimens between DM (N = 37) or PM (N = 36) subjects and healthy subjects (N = 14), respectively.
No statistical test was calculated in the RA comparison due to sample size (N = 2 vs. N = 20), although the trend
is apparent. Horizontal bars represent the median values for each group and the gray dashed line indicates the
threshold for signature positive or negative status.
in SSc). The population modeling using a relevant PD marker and stochastic simulations
greatly facilitated the bridging across different treatment periods, dosing methods, and
patient populations of the FTIH and the PoC studies.
The clinical development of a new drug is a lengthy and costly process with low odds
of success. Contrary to common impression, the clinical development of biotherapeutics is
not quicker or cheaper than that of small molecule drugs
[64,65]
. The early clinical develop-
ment of biotherapeutics, in particular Phase I, is much lengthier than for small molecules,
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