Appendix 1 Details of the Cox regression to estimate the probability of survival for the imputation
of censored QALYs
Cox regression was used to estimate the survival function and probability of survival at each assessment
point, using patient status (alive, dead or withdrawn) and treatment allocation. The QALY’s for this group
were estimated as:
QALYC= ((Ui + Ui+1)/2) ((Si + Si+1)/2) (ti+1 + ti),
where U = utility value, S = probability of survival and t = number of days between assessments.
The Cox regression was conducted in SPSS. Days observed alive in the trial was used as the time
variable. Treatment allocation was entered as a categorical variable. The results are presented below in
Table A.1.
Table A.1 Cox regression model coefficients
Omnibus Tests of Model Coefficients
-2 Log
Likelihood
Overall (score)
Chisquare
df
Sig.
72.04
6.58 6.00 0.36
Change From Previous Step
Chisquare
df
Sig.
8.72
6.00
0.19
Change From Previous
Block
Chisquare
df
Sig.
8.72
6.00
0.19
Cox regression uses the assumption that the shape of the survival function is the same for all groups, so
that although the time to an event may differ, the rate at which that event occurs is the same for all groups
is the same after the first event. A violation of this assumption occurs when there is an interaction
between the time variable and other covariate, such as treatment group. Table A.2 gives the results of the
analysis to assess whether this assumption of proportionality of hazards is violated. A time dependent
variable (time covariate) was defined as the natural logarithm of the observed days alive in the trial. This
was interacted with treatment allocation. The results indicate that the coefficients on the time covariate
and treatment allocation interaction were not significant. This indicates that the assumption of
proportionality of hazards is met.
Table A.2 Analysis of time dependent covariates to test assumption of proportional hazards
B
SE
Treatment allocation
Clozapine
-19.81 508.05
Other SGAs
14.85
25.69
Time covariate*Treatment allocation
Time
covariate*clozapine
2.53
44.25
Time covariate*Other
SGAs
1.05
12.37
Wald
df
p
Exp(B)
95.0% CI for Exp(B)
Lower
Upper
1.35
0.00
0.33
1.38
3.00
1.00
1.00
3.00
0.72
0.97
0.56
0.71
2.49E-09
2803200
0
3.83E-16
.
2.05E+28
0.00
1.00
0.95
12.51
2.7E-37
5.78E+38
0.01
1.00
0.93
2.86
8.53E-11
9.59E+10
Appendix 2 Average length of stay per person admitted to psychiatric hospital, complete case
analysis, unadjusted data
Location
Centre 1, Greater Manchester
Centre 2, Nottingham
Centre 3, South East London
Centre 4, North West London
Centre 5 Cambridge & Peterborough 5
Treatment arm
Clozapine
Other SGAs
Total
Clozapine
Other SGAs
Total
Clozapine
Other SGAs
Total
Clozapine
Other SGAs
Total
Clozapine
Other SGAs
Total
N
13
10
23
20
12
32
5
6
11
13
13
26
2
1
3
Mean
63
50
58
47
60
52
81
74
77
101
94
97
28
86
47
s.d.
27
33
30
30
39
34
33
38
34
19
31
25
16
.
36