Clozaril^®^ (clozapine) Tablets

Briefing Document for Psychopharmacological Drugs Advisory Committee
Meeting (June 16, 2003)

Appendix 2: Post-text Tables (United Kingdom Data)

  -------------------- --------------------------------------------------
  Document status:     Final

  Release date:        May 19, 2003

  Number of pages:     44
  -------------------- --------------------------------------------------

Available for public disclosure without redaction

Table of contents

1 Agranulocytosis incidence per 1,000 person-years and 95% CI, by
treatment duration, in the UK CPMS.
[4](#agranulocytosis-incidence-per-1000-person-years-and-95-ci-by-treatment-duration-in-the-uk-cpms.)

2 Agranulocytosis incidence per 1,000 person-years and 95% CI, by
calendar year and treatment duration, in the UK CPMS.
[5](#agranulocytosis-incidence-per-1000-person-years-and-95-ci-by-calendar-year-and-treatment-duration-in-the-uk-cpms.)

3 Agranulocytosis incidence per 1,000 person-years and 95% CI, by
treatment duration and monitoring frequency, in the UK CPMS.
[7](#agranulocytosis-incidence-per-1000-person-years-and-95-ci-by-treatment-duration-and-monitoring-frequency-in-the-uk-cpms.)

4 Agranulocytosis incidence per 1,000 person-years and 95% CI, by
calendar year (2-year intervals), treatment duration and monitoring
frequency, in the UK CPMS.
[8](#agranulocytosis-incidence-per-1000-person-years-and-95-ci-by-calendar-year-2-year-intervals-treatment-duration-and-monitoring-frequency-in-the-uk-cpms.)

5 Agranulocytosis incidence per 1,000 person-years and 95% CI, by
treatment duration and cohort in the UK CPMS.
[10](#agranulocytosis-incidence-per-1000-person-years-and-95-ci-by-treatment-duration-and-cohort-in-the-uk-cpms.)

6 Agranulocytosis incidence per 1,000 person-years and 95% CI, by
treatment duration, monitoring frequency and cohort in the UK CPMS.
[11](#agranulocytosis-incidence-per-1000-person-years-and-95-ci-by-treatment-duration-monitoring-frequency-and-cohort-in-the-uk-cpms.)

7 Severe leukopenia incidence per 1,000 person-years and 95% CI, by
treatment duration, in the UK CPMS.
[12](#severe-leukopenia-incidence-per-1000-person-years-and-95-ci-by-treatment-duration-in-the-uk-cpms.)

8 Severe leukopenia incidence per 1,000 person-years and 95% CI, by
calendar year and treatment duration, in the UK CPMS.
[13](#severe-leukopenia-incidence-per-1000-person-years-and-95-ci-by-calendar-year-and-treatment-duration-in-the-uk-cpms.)

9 Severe leukopenia incidence per 1,000 person-years and 95% CI, by
treatment duration and monitoring frequency, in the UK CPMS.
[14](#severe-leukopenia-incidence-per-1000-person-years-and-95-ci-by-treatment-duration-and-monitoring-frequency-in-the-uk-cpms.)

10 Severe leukopenia incidence per 1,000 person-years and 95% CI, by
calendar year (2-year intervals), treatment duration and monitoring
frequency, in the UK CPMS.
[15](#severe-leukopenia-incidence-per-1000-person-years-and-95-ci-by-calendar-year-2-year-intervals-treatment-duration-and-monitoring-frequency-in-the-uk-cpms.)

11 Severe leukopenia incidence per 1,000 person-years and 95% CI, by
treatment duration and cohort in the UK CPMS.
[17](#severe-leukopenia-incidence-per-1000-person-years-and-95-ci-by-treatment-duration-and-cohort-in-the-uk-cpms.)

12 Severe leukopenia incidence per 1,000 person-years and 95% CI, by
treatment duration, monitoring frequency and cohort in the UK CPMS.
[18](#severe-leukopenia-incidence-per-1000-person-years-and-95-ci-by-treatment-duration-monitoring-frequency-and-cohort-in-the-uk-cpms.)

13 Red Alert incidence per 1,000 person-years and 95% CI, by treatment
duration, in the UK CPMS.
[19](#red-alert-incidence-per-1000-person-years-and-95-ci-by-treatment-duration-in-the-uk-cpms.)

14 Red alert incidence per 1,000 person-years and 95% CI, by calendar
year and treatment duration (3 periods), in the UK CPMS.
[20](#red-alert-incidence-per-1000-person-years-and-95-ci-by-calendar-year-and-treatment-duration-3-periods-in-the-uk-cpms.)

15 Red alert incidence per 1,000 person-years and 95% CI, by calendar
year and treatment duration (12 periods), in the UK CPMS.
[22](#red-alert-incidence-per-1000-person-years-and-95-ci-by-calendar-year-and-treatment-duration-12-periods-in-the-uk-cpms.)

16 Red alert incidence per 1,000 person-years and 95% CI, by treatment
duration and monitoring frequency, in the UK CPMS.
[27](#red-alert-incidence-per-1000-person-years-and-95-ci-by-treatment-duration-and-monitoring-frequency-in-the-uk-cpms.)

17 Red alert incidence per 1,000 person-years and 95% CI, by calendar
year (2-year intervals), treatment duration and monitoring frequency, in
the UK CPMS.
[28](#red-alert-incidence-per-1000-person-years-and-95-ci-by-calendar-year-2-year-intervals-treatment-duration-and-monitoring-frequency-in-the-uk-cpms.)

18 Red alert incidence per 1,000 person-years and 95% CI, by treatment
duration and cohort in the UK CPMS.
[30](#red-alert-incidence-per-1000-person-years-and-95-ci-by-treatment-duration-and-cohort-in-the-uk-cpms.)

19 Red alert incidence per 1,000 person-years and 95% CI, by treatment
duration, monitoring frequency and cohort in the UK CPMS.
[31](#red-alert-incidence-per-1000-person-years-and-95-ci-by-treatment-duration-monitoring-frequency-and-cohort-in-the-uk-cpms.)

20 Red alert treatment withdrawal criteria, in the UK CPMS
[33](#red-alert-treatment-withdrawal-criteria-in-the-uk-cpms)

21 Demographic characteristics of the UK CPMS patients included in the
analysis, by cohort.
[34](#demographic-characteristics-of-the-uk-cpms-patients-included-in-the-analysis-by-cohort.)

22 Demographic characteristics of the UK CPMS patients with
agranulocytosis , by cohort.
[35](#demographic-characteristics-of-the-uk-cpms-patients-with-agranulocytosis-by-cohort.)

23 Demographic characteristics of the UK CPMS patients with severe
leukopenia, by cohort.
[36](#demographic-characteristics-of-the-uk-cpms-patients-with-severe-leukopenia-by-cohort.)

24 Demographic characteristics of the UK CPMS patients with red alert,
by cohort.
[37](#demographic-characteristics-of-the-uk-cpms-patients-with-red-alert-by-cohort.)

Figures [38](#figures)

1\) Agranulocytosis incidence per 1,000 person years and 95% CI, for the
first 84 weeks of treatment (in 2-week intervals).
[39](#agranulocytosis-incidence-per-1000-person-years-and-95-ci-for-the-first-84-weeks-of-treatment-in-2-week-intervals.)

2\) Agranulocytosis incidence per 1,000 person years and 95% CI, by
treatment duration (in 6-week intervals).
[40](#agranulocytosis-incidence-per-1000-person-years-and-95-ci-by-treatment-duration-in-6-week-intervals.)

3\) Severe leukopenia incidence per 1,000 person years and 95% CI, for
the first 84 weeks of treatment (in 2-week intervals).
[41](#severe-leukopenia-incidence-per-1000-person-years-and-95-ci-for-the-first-84-weeks-of-treatment-in-2-week-intervals.)

4\) Severe leukopenia incidence per 1,000 person years and 95% CI, by
treatment duration (in 6-week intervals).
[42](#severe-leukopenia-incidence-per-1000-person-years-and-95-ci-by-treatment-duration-in-6-week-intervals.)

5\) Red alert incidence per 1,000 person years and 95% CI, for the first
84 weeks of treatment (in 2-week intervals).
[43](#red-alert-incidence-per-1000-person-years-and-95-ci-for-the-first-84-weeks-of-treatment-in-2-week-intervals.)

6\) Red alert incidence per 1,000 person years and 95% CI, by treatment
duration (in 6-week intervals).
[44](#red-alert-incidence-per-1000-person-years-and-95-ci-by-treatment-duration-in-6-week-intervals.)

#   {#section .unnumbered}

# 1 Agranulocytosis incidence per 1,000 person-years and 95% CI, by treatment duration, in the UK CPMS. 

  ------------------------------------------------------------------------
  **Table 4.1.                                                    
  Agranulocytosis                                                 
  incidence per                                                   
  1,000                                                           
  person-years and                                                
  95% CI, by                                                      
  treatment                                                       
  duration, in the                                                
  UK CPMS.**                                                      
  ----------------- -------- ------------- ------------- -------- --------
                    Cases    Pat-yrs       Incidence     95%      CI

  Trt duration      162      7,579.46      21.37         18.08    24.66

  0-18 wks                                                        

  19-52 wks         16       11,147.43     1.44          0.82     2.33

  +52 wks           40       56,757.91     0.70          0.49     0.92
  ------------------------------------------------------------------------

# 2 Agranulocytosis incidence per 1,000 person-years and 95% CI, by calendar year and treatment duration, in the UK CPMS. 

  ---------------------------------------------------------------------------------
  **Table 4.2.                                                              
  Agranulocytosis                                                           
  incidence per                                                             
  1,000                                                                     
  person-years and                                                          
  95% CI, by                                                                
  calendar year and                                                         
  treatment                                                                 
  duration, in the                                                          
  UK CPMS.**                                                                
  ----------------- --------------- ------- ----------- ----------- ------- -------
                                    Cases   Pat-yrs     Incidence   95%     CI

  trt duration      Calendar year   4       131.03      30.53       8.32    78.15

  0-18 wks          1990                                                    

                    1991            7       394.33      17.75       7.14    36.57

                    1992            11      415.40      26.48       13.22   47.38

                    1993            11      421.84      26.08       13.02   46.65

                    1994            15      430.83      34.82       19.49   57.42

                    1995            13      592.05      21.96       11.69   37.55

                    1996            18      765.97      23.50       13.93   37.14

                    1997            4       574.28      6.97        1.90    17.83

                    1998            19      765.86      24.81       14.94   38.74

                    1999            29      945.67      30.67       19.50   41.83

                    2000            19      969.67      19.59       11.80   30.60

                    2001            12      1,010.03    11.88       6.14    20.75

                    2002            .       162.50      .           .       .

  19-52 wks         1990            .       56.70       .           .       .

                    1991            1       374.28      2.67        0.07    14.89

                    1992            .       630.79      .           .       .

                    1993            2       662.72      3.02        0.37    10.90

                    1994            .       585.94      .           .       .

                    1995            1       797.02      1.25        0.03    6.99

                    1996            2       1,159.13    1.73        0.21    6.23

                    1997            2       994.78      2.01        0.24    7.26

                    1998            3       1,037.32    2.89        0.60    8.45

                    1999            2       1,430.98    1.40        0.17    5.05

                    2000            2       1,499.66    1.33        0.16    4.82

                    2001            1       1,645.98    0.61        0.02    3.39

                    2002            .       272.15      .           .       .

  +52 wks           1990            .       1.69        .           .       .

                    1991            .       141.41      .           .       .

                    1992            1       747.61      1.34        0.03    7.45

                    1993            .       1,572.48    .           .       .

                    1994            1       2,302.91    0.43        0.01    2.42

                    1995            1       3,009.96    0.33        0.01    1.85

                    1996            3       4,232.59    0.71        0.15    2.07

                    1997            4       5,535.94    0.72        0.20    1.85

                    1998            4       6,718.51    0.60        0.16    1.52

                    1999            9       8,129.39    1.11        0.51    2.10

                    2000            10      10,091.22   0.99        0.48    1.82

                    2001            7       12,077.15   0.58        0.23    1.19

                    2002            .       2,197.04    .           .       .
  ---------------------------------------------------------------------------------

# 

# 3 Agranulocytosis incidence per 1,000 person-years and 95% CI, by treatment duration and monitoring frequency, in the UK CPMS.

  -----------------------------------------------------------------------------------
  **Table 4.3.                                                                
  Agranulocytosis                                                             
  incidence per                                                               
  1,000                                                                       
  person-years and                                                            
  95% CI by                                                                   
  treatment                                                                   
  duration and                                                                
  monitoring                                                                  
  frequency, in the                                                           
  UK CPMS.**                                                                  
  ----------------- ----------------- ------- ----------- ----------- ------- -------
                                      Cases   Pat-yrs     Incidence   95%     CI

  trt duration      Monitoring freq.  162     7,575.17    21.39       18.09   24.68

  0-18 wks          1W                                                        

  19-52 wks         1W                12      2,506.63    4.79        2.47    8.36

                    2W                4       8,616.53    0.46        0.13    1.19

  +52 wks           1W                17      2,518.03    6.75        3.93    10.81

                    2W                6       10,978.36   0.55        0.20    1.19

                    4W                17      43,181.76   0.39        0.23    0.63
  -----------------------------------------------------------------------------------

1W - patients who were monitored weekly

2W - patients who were monitored every two weeks

4W - patients who were monitored every four weeks (monthly)

# 4 Agranulocytosis incidence per 1,000 person-years and 95% CI, by calendar year (2-year intervals), treatment duration and monitoring frequency, in the UK CPMS.

  -----------------------------------------------------------------------------------------
  **Table 4.4.                                                                      
  Agranulocytosis                                                                   
  incidence per                                                                     
  1,000                                                                             
  person-years and                                                                  
  95% CI, by                                                                        
  calendar year                                                                     
  (2-year                                                                           
  intervals),                                                                       
  treatment                                                                         
  duration and                                                                      
  monitoring                                                                        
  frequency, in the                                                                 
  UK CPMS.**                                                                        
  ----------------- --------- ------------- ------- ----------- ----------- ------- -------
                                            Cases   Pat-yrs     Incidence   95%     CI

  trt duration      monitor   Calendar year 11      524.90      20.96       10.46   37.49

  0-18 wks          1W        1990-1991                                             

                              1992-1993     22      836.64      26.30       15.31   37.28

                              1994-1995     28      1,022.03    27.40       17.25   37.54

                              1996-1997     22      1,339.29    16.43       9.56    23.29

                              1998-1999     48      1,710.74    28.06       20.12   36.00

                              2000-2002\*   31      2,141.58    14.48       9.38    19.57

  19-52 wks         1W        1990-1991     1       115.98      8.62        0.22    48.04

                              1992-1993     2       295.12      6.78        0.82    24.48

                              1994-1995     1       315.53      3.17        0.08    17.66

                              1996-1997     3       472.24      6.35        1.31    18.56

                              1998-1999     3       577.84      5.19        1.07    15.17

                              2000-2002\*   2       729.92      2.74        0.33    9.90

                    2W        1990-1991     .       314.03      .           .       .

                              1992-1993     .       995.66      .           .       .

                              1994-1995     .       1,064.82    .           .       .

                              1996-1997     1       1,677.30    0.60        0.01    3.32

                              1998-1999     2       1,884.78    1.06        0.13    3.83

                              2000-2002\*   1       2,679.93    0.37        0.01    2.08

  +52 wks           1W        1990-1991     .       13.73       .           .       .

                              1992-1993     .       207.76      .           .       .

                              1994-1995     2       346.71      5.77        0.70    20.84

                              1996-1997     1       434.40      2.30        0.06    12.83

                              1998-1999     6       646.84      9.28        3.40    20.19

                              2000-2002\*   8       868.59      9.21        3.98    18.14

                    2W        1990-1991     .       128.91      .           .       .

                              1992-1993     1       2,107.50    0.47        0.01    2.64

                              1994-1995     .       3,828.73    .           .       .

                              1996-1997     2       1,524.43    1.31        0.16    4.74

                              1998-1999     1       1,594.00    0.63        0.02    3.50

                              2000-2002\*   2       1,794.79    1.11        0.13    4.03

                    4W        1994-1995     .       1,128.30    .           .       .

                              1996-1997     4       7,795.15    0.51        0.14    1.31

                              1998-1999     6       12,586.90   0.48        0.17    1.04

                              2000-2002\*   7       21,671.41   0.32        0.13    0.67
  -----------------------------------------------------------------------------------------

1W - patients who were monitored weekly

2W - patients who were monitored every two weeks

4W - patients who were monitored every four weeks (monthly)

#  

# 5 Agranulocytosis incidence per 1,000 person-years and 95% CI, by treatment duration and cohort in the UK CPMS.

  -------------------------------------------------------------------------------------
  **Table 4.5.                                                                  
  Agranulocytosis                                                               
  incidence per                                                                 
  1,000                                                                         
  person-years and                                                              
  95% CI, by                                                                    
  treatment                                                                     
  duration and                                                                  
  cohort in the UK                                                              
  CPMS.**                                                                       
  ----------------- ------------------- ------- ----------- ----------- ------- -------
                                        Cases   Pat-yrs     Incidence   95%     CI

  Trt duration      Cohort              43      1,731.75    24.83       17.41   32.25

  0-18 wks          Initial system                                              

                    Current system, new 119     5,839.83    20.38       16.72   24.04
                    patients                                                    

                    Current system, old .       1.20        .           .       .
                    patients                                                    

  19-52 wks         Initial system      3       2,586.62    1.16        0.24    3.39

                    Current system, new 13      8,552.11    1.52        0.81    2.60
                    patients                                                    

                    Current system, old .       3.14        .           .       .
                    patients                                                    

  +52 wks           Initial system      2       6,542.55    0.31        0.04    1.10

                    Current system, new 18      30,693.75   0.59        0.35    0.93
                    patients                                                    

                    Current system, old 20      19,499.30   1.03        0.63    1.58
                    patients                                                    
  -------------------------------------------------------------------------------------

# 6 Agranulocytosis incidence per 1,000 person-years and 95% CI, by treatment duration, monitoring frequency and cohort in the UK CPMS.

  ----------------------------------------------------------------------------------------
  **Table 4.6.                                                                     
  Agranulocytosis                                                                  
  incidence per                                                                    
  1,000                                                                            
  person-years and                                                                 
  95% CI, by                                                                       
  treatment                                                                        
  duration,                                                                        
  monitoring                                                                       
  frequency and                                                                    
  cohort style, in                                                                 
  the US CPMS.**                                                                   
  ----------------- --------- ------------ ------- ----------- ----------- ------- -------
                                           Cases   Pat-yrs     Incidence   95%     CI

  Trt duration      monitor   Cohort       43      1,730.38    24.85       17.42   32.28

  0-18 wks          1W        Initial                                              
                              system                                               

                              Current      119     5,836.92    20.39       16.72   24.05
                              system, new                                          
                              patients                                             

                              Current      .       1.20        .           .       .
                              system, old                                          
                              patients                                             

  19-52 wks         1W        Initial      3       576.70      5.20        1.07    15.20
                              system                                               

                              Current      9       1,927.84    4.67        2.13    8.86
                              system, new                                          
                              patients                                             

                              Current      .       0.79        .           .       .
                              system, old                                          
                              patients                                             

                    2W        Initial      .       2,004.42    .           .       .
                              system                                               

                              Current      4       6,605.80    0.61        0.17    1.55
                              system, new                                          
                              patients                                             

                              Current      .       2.05        .           .       .
                              system, old                                          
                              patients                                             

  +52 wks           1W        Initial      1       492.97      2.03        0.05    11.30
                              system                                               

                              Current      6       1,303.73    4.60        1.69    10.02
                              system, new                                          
                              patients                                             

                              Current      10      718.72      13.91       6.67    25.59
                              system, old                                          
                              patients                                             

                    2W        Initial      1       6,038.57    0.17        0.00    0.92
                              system                                               

                              Current      3       3,310.65    0.91        0.19    2.65
                              system, new                                          
                              patients                                             

                              Current      2       1,625.35    1.23        0.15    4.45
                              system, old                                          
                              patients                                             

                    4W        Current      9       26,034.87   0.35        0.16    0.66
                              system, new                                          
                              patients                                             

                              Current      8       17,131.16   0.47        0.20    0.92
                              system, old                                          
                              patients                                             
  ----------------------------------------------------------------------------------------

1W - patients who were monitored weekly

2W - patients who were monitored every two weeks

4W - patients who were monitored every four weeks (monthly)

# 

# 7 Severe leukopenia incidence per 1,000 person-years and 95% CI, by treatment duration, in the UK CPMS. 

  ------------------------------------------------------------------------
  **Table 4.7.                                                    
  Severe leukopenia                                               
  incidence per                                                   
  1,000                                                           
  person-years and                                                
  95% CI, by                                                      
  treatment                                                       
  duration, in the                                                
  UK CPMS.**                                                      
  ----------------- -------- ------------- ------------- -------- --------
                    Cases    Pat-yrs       Incidence     95%      CI

  trt duration      244      7,579.46      32.19         28.15    36.23

  0-18 wks                                                        

  19-52 wks         45       11,147.43     4.04          2.86     5.22

  +52 wks           111      56,757.91     1.96          1.59     2.32
  ------------------------------------------------------------------------

# 8 Severe leukopenia incidence per 1,000 person-years and 95% CI, by calendar year and treatment duration, in the UK CPMS.

  ------------------------------------------------------------------------------
  **Table 4.8.                                                          
  Severe                                                                
  leukopenia                                                            
  incidence per                                                         
  1,000                                                                 
  person-years                                                          
  and 95% CI, by                                                        
  calendar year                                                         
  and treatment                                                         
  duration, in                                                          
  the UK CPMS.**                                                        
  -------------- -------------- ------- ----------- ----------- ------- --------
                                Cases   Pat-yrs     Incidence   95%     CI

  Trt duration   Calendar year  7       131.03      53.42       21.48   110.05

  0-18 wks       1990                                                   

                 1991           12      394.33      30.43       15.73   53.15

                 1992           14      415.40      33.70       18.43   56.55

                 1993           13      421.84      30.82       16.41   52.70

                 1994           18      430.83      41.78       24.77   66.03

                 1995           18      592.05      30.40       18.02   48.05

                 1996           22      765.97      28.72       16.72   40.72

                 1997           15      574.28      26.12       14.62   43.08

                 1998           27      765.86      35.25       21.96   48.55

                 1999           44      945.67      46.53       32.78   60.28

                 2000           26      969.67      26.81       16.51   37.12

                 2001           22      1,010.03    21.78       12.68   30.88

                 2002           6       162.50      36.92       13.55   80.37

  19-52 wks      1990           .       56.70       .           .       .

                 1991           2       374.28      5.34        0.65    19.30

                 1992           3       630.79      4.76        0.98    13.90

                 1993           4       662.72      6.04        1.64    15.45

                 1994           1       585.94      1.71        0.04    9.51

                 1995           3       797.02      3.76        0.78    11.00

                 1996           4       1,159.13    3.45        0.94    8.83

                 1997           5       994.78      5.03        1.63    11.73

                 1998           6       1,037.32    5.78        2.12    12.59

                 1999           5       1,430.98    3.49        1.13    8.16

                 2000           7       1,499.66    4.67        1.88    9.62

                 2001           4       1,645.98    2.43        0.66    6.22

                 2002           1       272.15      3.67        0.09    20.47

  +52 wks        1990           .       1.69        .           .       .

                 1991           1       141.41      7.07        0.18    39.40

                 1992           3       747.61      4.01        0.83    11.73

                 1993           4       1,572.48    2.54        0.69    6.51

                 1994           5       2,302.91    2.17        0.70    5.07

                 1995           3       3,009.96    1.00        0.21    2.91

                 1996           8       4,232.59    1.89        0.82    3.72

                 1997           8       5,535.94    1.45        0.62    2.85

                 1998           14      6,718.51    2.08        1.14    3.50

                 1999           19      8,129.39    2.34        1.41    3.65

                 2000           27      10,091.22   2.68        1.67    3.68

                 2001           17      12,077.15   1.41        0.82    2.25

                 2002           2       2,197.04    0.91        0.11    3.29
  ------------------------------------------------------------------------------

# 9 Severe leukopenia incidence per 1,000 person-years and 95% CI, by treatment duration and monitoring frequency, in the UK CPMS.

  -------------------------------------------------------------------------
  **Table 4.9.                                                      
  Severe                                                            
  leukopenia                                                        
  incidence per                                                     
  1,000                                                             
  person-years                                                      
  and 95% CI, by                                                    
  treatment                                                         
  duration and                                                      
  monitoring                                                        
  frequency, in                                                     
  the UK CPMS.**                                                    
  --------------- --------- ------- ----------- ----------- ------- -------
                            Cases   Pat-yrs     Incidence   95%     CI

  Trt duration    Monitor   244     7,575.17    32.21       28.17   36.25

  0-18 wks        1W                                                

  19-52 wks       1W        39      2,506.63    15.56       10.68   20.44

                  2W        6       8,616.53    0.70        0.26    1.52

  +52 wks         1W        72      2,518.03    28.59       21.99   35.20

                  2W        13      10,978.36   1.18        0.63    2.02

                  4W        25      43,181.76   0.58        0.35    0.81
  -------------------------------------------------------------------------

# 10 Severe leukopenia incidence per 1,000 person-years and 95% CI, by calendar year (2-year intervals), treatment duration and monitoring frequency, in the UK CPMS.

  ---------------------------------------------------------------------------------------
  **Table 4.10.                                                                  
  Severe                                                                         
  leukopenia                                                                     
  incidence per                                                                  
  1,000                                                                          
  person-years                                                                   
  and 95% CI, by                                                                 
  calendar year                                                                  
  (2-year                                                                        
  intervals),                                                                    
  treatment                                                                      
  duration and                                                                   
  monitoring                                                                     
  frequency, in                                                                  
  the UK CPMS.**                                                                 
  -------------- --------- ------------- ------- ----------- ----------- ------- --------
                                         Cases   Pat-yrs     Incidence   95%     CI

  trt duration   monitor   Calendar year 19      524.90      36.20       21.79   56.53

  0-18 wks       1W        1990-1991                                             

                           1992-1993     27      836.64      32.27       20.10   44.44

                           1994-1995     36      1,022.03    35.22       23.72   46.73

                           1996-1997     37      1,339.29    27.63       18.72   36.53

                           1998-1999     71      1,710.74    41.50       31.85   51.16

                           2000-2002\*   54      2,141.58    25.22       18.49   31.94

  19-52 wks      1W        1990-1991     1       115.98      8.62        0.22    48.04

                           1992-1993     7       295.12      23.72       9.54    48.86

                           1994-1995     4       315.53      12.68       3.45    32.45

                           1996-1997     7       472.24      14.82       5.96    30.54

                           1998-1999     10      577.84      17.31       8.30    31.83

                           2000-2002\*   10      729.92      13.70       6.57    25.19

                 2W        1990-1991     1       314.03      3.18        0.08    17.74

                           1992-1993     .       995.66      .           .       .

                           1994-1995     .       1,064.82    .           .       .

                           1996-1997     2       1,677.30    1.19        0.14    4.31

                           1998-1999     1       1,884.78    0.53        0.01    2.96

                           2000-2002\*   2       2,679.93    0.75        0.09    2.70

  +52 wks        1W        1990-1991     1       13.73       72.83       1.82    405.82

                           1992-1993     4       207.76      19.25       5.25    49.29

                           1994-1995     4       346.71      11.54       3.14    29.53

                           1996-1997     11      434.40      25.32       12.64   45.30

                           1998-1999     24      646.84      37.10       22.26   51.95

                           2000-2002\*   28      868.59      32.24       20.30   44.18

                 2W        1990-1991     .       128.91      .           .       .

                           1992-1993     3       2,107.50    1.42        0.29    4.16

                           1994-1995     4       3,828.73    1.04        0.28    2.67

                           1996-1997     1       1,524.43    0.66        0.02    3.66

                           1998-1999     2       1,594.00    1.25        0.15    4.53

                           2000-2002\*   3       1,794.79    1.67        0.34    4.88

                 4W        1994-1995     .       1,128.30    .           .       .

                           1996-1997     4       7,795.15    0.51        0.14    1.31

                           1998-1999     7       12,586.90   0.56        0.22    1.15

                           2000-2002\*   14      21,671.41   0.65        0.35    1.08
  ---------------------------------------------------------------------------------------

1W - patients who were monitored weekly

2W - patients who were monitored every two weeks

4W - patients who were monitored every four weeks (monthly)

# 11 Severe leukopenia incidence per 1,000 person-years and 95% CI, by treatment duration and cohort in the UK CPMS.

  ----------------------------------------------------------------------------------
  **Table 4.11.                                                              
  Severe                                                                     
  leukopenia                                                                 
  incidence per                                                              
  1,000                                                                      
  person-years                                                               
  and 95% CI, by                                                             
  treatment                                                                  
  duration and                                                               
  cohort in the                                                              
  UK CPMS.**                                                                 
  -------------- ------------------- ------- ----------- ----------- ------- -------
                                     Cases   Pat-yrs     Incidence   95%     CI

  trt duration   Cohort              58      1,731.75    33.49       24.87   42.11

  0-18 wks       Initial system                                              

                 Current system, new 186     5,839.83    31.85       27.27   36.43
                 patients                                                    

                 Current system, old .       1.20        .           .       .
                 patients                                                    

  19-52 wks      Initial system      11      2,586.62    4.25        2.12    7.61

                 Current system, new 34      8,552.11    3.98        2.64    5.31
                 patients                                                    

                 Current system, old .       3.14        .           .       .
                 patients                                                    

  +52 wks        Initial system      17      6,542.55    2.60        1.51    4.16

                 Current system, new 58      30,693.75   1.89        1.40    2.38
                 patients                                                    

                 Current system, old 34      19,499.30   1.74        1.16    2.33
                 patients                                                    
  ----------------------------------------------------------------------------------

# 12 Severe leukopenia incidence per 1,000 person-years and 95% CI, by treatment duration, monitoring frequency and cohort in the UK CPMS.

  -------------------------------------------------------------------------------------
  **Table 4.12.                                                                 
  Severe                                                                        
  leukopenia                                                                    
  incidence per                                                                 
  1,000                                                                         
  person-years                                                                  
  and 95% CI, by                                                                
  treatment                                                                     
  duration,                                                                     
  monitoring                                                                    
  frequency and                                                                 
  cohort in the                                                                 
  UK CPMS.**                                                                    
  -------------- --------- ------------ ------- ----------- ----------- ------- -------
                                        Cases   Pat-yrs     Incidence   95%     CI

  Trt duration   monitor   Cohort       58      1,730.38    33.52       24.89   42.15

  0-18 wks       1W        Initial                                              
                           system                                               

                           Current      186     5,836.92    31.87       27.29   36.45
                           system, new                                          
                           patients                                             

                           Current      .       1.20        .           .       .
                           system, old                                          
                           patients                                             

  19-52 wks      1W        Initial      10      576.70      17.34       8.31    31.89
                           system                                               

                           Current      29      1,927.84    15.04       9.57    20.52
                           system, new                                          
                           patients                                             

                           Current      .       0.79        .           .       .
                           system, old                                          
                           patients                                             

                 2W        Initial      1       2,004.42    0.50        0.01    2.78
                           system                                               

                           Current      5       6,605.80    0.76        0.25    1.77
                           system, new                                          
                           patients                                             

                           Current      .       2.05        .           .       .
                           system, old                                          
                           patients                                             

  +52 wks        1W        Initial      10      492.97      20.29       9.73    37.30
                           system                                               

                           Current      38      1,303.73    29.15       19.88   38.41
                           system, new                                          
                           patients                                             

                           Current      22      718.72      30.61       17.82   43.40
                           system, old                                          
                           patients                                             

                 2W        Initial      7       6,038.57    1.16        0.47    2.39
                           system                                               

                           Current      4       3,310.65    1.21        0.33    3.09
                           system, new                                          
                           patients                                             

                           Current      2       1,625.35    1.23        0.15    4.45
                           system, old                                          
                           patients                                             

                 4W        Current      16      26,034.87   0.61        0.35    1.00
                           system, new                                          
                           patients                                             

                           Current      9       17,131.16   0.53        0.24    1.00
                           system, old                                          
                           patients                                             
  -------------------------------------------------------------------------------------

1W - patients who were monitored weekly

2W - patients who were monitored every two weeks

4W - patients who were monitored every four weeks (monthly)

# 13 Red Alert incidence per 1,000 person-years and 95% CI, by treatment duration, in the UK CPMS. 

  ------------------------------------------------------------------------
  **Table 4.13. Red                                               
  alert incidence                                                 
  per 1,000                                                       
  person-years and                                                
  95% CI, by                                                      
  treatment                                                       
  duration, in the                                                
  UK CPMS.**                                                      
  ----------------- -------- ------------- ------------- -------- --------
                    Cases    Pat-yrs       Incidence     95%      CI

  trt duration      664      7,579.46      87.61         80.94    94.27

  0-18 wks                                                        

  19-52 wks         256      11,147.43     22.96         20.15    25.78

  +52 wks           421      56,757.91     7.42          6.71     8.13
  ------------------------------------------------------------------------

# 14 Red alert incidence per 1,000 person-years and 95% CI, by calendar year and treatment duration (3 periods), in the UK CPMS.

  ------------------------------------------------------------------------------
  **Table 4.14.                                                         
  Red alert                                                             
  incidence per                                                         
  1,000                                                                 
  person-years                                                          
  and 95% CI, by                                                        
  calendar year                                                         
  and treatment                                                         
  duration (3                                                           
  periods), in                                                          
  the UK CPMS.**                                                        
  -------------- -------------- ------- ----------- ----------- ------- --------
                                Cases   Pat-yrs     Incidence   95%     CI

  Trt duration   Calendar year  17      131.03      129.74      75.58   207.74

  0-18 wks       1990                                                   

                 1991           44      394.33      111.58      78.61   144.55

                 1992           42      415.40      101.11      70.53   131.68

                 1993           46      421.84      109.05      77.53   140.56

                 1994           47      430.83      109.09      77.90   140.28

                 1995           54      592.05      91.21       66.88   115.54

                 1996           61      765.97      79.64       59.65   99.62

                 1997           40      574.28      69.65       48.07   91.24

                 1998           73      765.86      95.32       73.45   117.18

                 1999           88      945.67      93.06       73.61   112.50

                 2000           75      969.67      77.35       59.84   94.85

                 2001           64      1,010.03    63.36       47.84   78.89

                 2002           12      162.50      73.85       38.16   128.98

  19-52 wks      1990           2       56.70       35.27       4.27    127.43

                 1991           14      374.28      37.41       20.45   62.76

                 1992           18      630.79      28.54       16.92   45.10

                 1993           29      662.72      43.76       27.83   59.69

                 1994           8       585.94      13.65       5.89    26.90

                 1995           19      797.02      23.84       14.35   37.23

                 1996           23      1,159.13    19.84       11.73   27.95

                 1997           18      994.78      18.09       10.73   28.60

                 1998           31      1,037.32    29.88       19.36   40.41

                 1999           31      1,430.98    21.66       14.04   29.29

                 2000           25      1,499.66    16.67       10.14   23.21

                 2001           34      1,645.98    20.66       13.71   27.60

                 2002           4       272.15      14.70       4.01    37.63

  +52 wks        1990           .       1.69        .           .       .

                 1991           2       141.41      14.14       1.71    51.09

                 1992           11      747.61      14.71       7.34    26.32

                 1993           22      1,572.48    13.99       8.14    19.84

                 1994           24      2,302.91    10.42       6.25    14.59

                 1995           25      3,009.96    8.31        5.05    11.56

                 1996           27      4,232.59    6.38        3.97    8.79

                 1997           37      5,535.94    6.68        4.53    8.84

                 1998           38      6,718.51    5.66        3.86    7.45

                 1999           63      8,129.39    7.75        5.84    9.66

                 2000           74      10,091.22   7.33        5.66    9.00

                 2001           84      12,077.15   6.96        5.47    8.44

                 2002           14      2,197.04    6.37        3.48    10.69
  ------------------------------------------------------------------------------

# 15 Red alert incidence per 1,000 person-years and 95% CI, by calendar year and treatment duration (12 periods), in the UK CPMS.

  ------------------------------------------------------------------------------
  **Table 4.15.                                                         
  Red alert                                                             
  incidence per                                                         
  1,000                                                                 
  person-years                                                          
  and 95% CI, by                                                        
  calendar year                                                         
  and treatment                                                         
  duration (12                                                          
  periods), in                                                          
  the UK CPMS.**                                                        
  -------------- --------------- ------- ---------- ----------- ------- --------
                                 Cases   Pat-yrs    Incidence   95%     CI

  Trt duration   Calendar year   18      156.61     114.94      68.13   181.66

  0-6 months     1990                                                   

                 1991            49      515.49     95.05       68.44   121.67

                 1992            46      572.54     80.34       57.13   103.56

                 1993            56      586.39     95.50       70.49   120.51

                 1994            50      583.93     85.63       61.89   109.36

                 1995            64      803.47     79.65       60.14   99.17

                 1996            71      1,066.48   66.57       51.09   82.06

                 1997            50      797.96     62.66       45.29   80.03

                 1998            84      1,037.57   80.96       63.65   98.27

                 1999            102     1,307.23   78.03       62.88   93.17

                 2000            83      1,332.41   62.29       48.89   75.69

                 2001            76      1,408.42   53.96       41.83   66.09

                 2002            14      225.69     62.03       33.91   104.08

  6-12 months    1990            1       31.12      32.14       0.80    179.06

                 1991            9       253.12     35.56       16.26   67.52

                 1992            14      473.65     29.56       16.16   49.59

                 1993            19      498.17     38.14       22.96   59.56

                 1994            5       432.85     11.55       3.75    26.96

                 1995            9       585.60     15.37       7.03    29.18

                 1996            13      858.63     15.14       8.06    25.89

                 1997            8       771.10     10.37       4.48    20.44

                 1998            20      765.61     26.12       15.96   40.35

                 1999            17      1,069.42   15.90       9.26    25.45

                 2000            17      1,136.91   14.95       8.71    23.94

                 2001            22      1,247.58   17.63       10.27   25.00

                 2002            2       208.96     9.57        1.16    34.58

  1-2 yrs        1990            .       1.69       .           .       .

                 1991            2       139.85     14.30       1.73    51.66

                 1992            10      615.56     16.25       7.79    29.88

                 1993            11      880.96     12.49       6.23    22.34

                 1994            12      865.40     13.87       7.17    24.22

                 1995            4       844.15     4.74        1.29    12.13

                 1996            9       1,201.30   7.49        3.43    14.23

                 1997            13      1,551.52   8.38        4.46    14.33

                 1998            9       1,343.70   6.70        3.06    12.72

                 1999            12      1,536.78   7.81        4.04    13.64

                 2000            20      2,069.81   9.66        5.90    14.92

                 2001            20      2,137.51   9.36        5.72    14.45

                 2002            2       385.31     5.19        0.63    18.75

  2-3 yrs        1991            .       1.56       .           .       .

                 1992            1       130.91     7.64        0.19    42.56

                 1993            9       567.66     15.85       7.25    30.11

                 1994            9       784.19     11.48       5.25    21.79

                 1995            9       785.30     11.46       5.24    21.76

                 1996            5       830.19     6.02        1.95    14.06

                 1997            5       1,085.79   4.60        1.49    10.75

                 1998            10      1,480.25   6.76        3.24    12.42

                 1999            13      1,306.44   9.95        5.30    17.02

                 2000            5       1,498.00   3.34        1.08    7.79

                 2001            18      2,000.27   9.00        5.33    14.22

                 2002            4       328.92     12.16       3.31    31.13

  3-4 yrs        1992            .       1.14       .           .       .

                 1993            2       122.71     16.30       1.97    58.88

                 1994            3       532.89     5.63        1.16    16.45

                 1995            7       750.70     9.32        3.75    19.21

                 1996            2       791.33     2.53        0.31    9.13

                 1997            4       785.56     5.09        1.39    13.04

                 1998            5       1,050.66   4.76        1.54    11.11

                 1999            11      1,433.33   7.67        3.83    13.73

                 2000            11      1,277.78   8.61        4.30    15.40

                 2001            10      1,459.22   6.85        3.29    12.60

                 2002            2       296.60     6.74        0.82    24.36

  4-5 yrs        1992            .       .          .           .       .

                 1993            .       1.15       .           .       .

                 1994            .       119.33     .           .       .

                 1995            5       512.37     9.76        3.17    22.78

                 1996            8       760.57     10.52       4.54    20.72

                 1997            7       758.19     9.23        3.71    19.02

                 1998            8       767.03     10.43       4.50    20.55

                 1999            9       1,023.35   8.79        4.02    16.70

                 2000            16      1,412.07   11.33       6.48    18.40

                 2001            10      1,259.16   7.94        3.81    14.60

                 2002            2       208.53     9.59        1.16    34.65

  5-6 yrs        1994            .       1.09       .           .       .

                 1995            .       116.32     .           .       .

                 1996            1       526.84     1.90        0.05    10.58

                 1997            4       724.06     5.52        1.51    14.14

                 1998            5       737.86     6.78        2.20    15.82

                 1999            6       759.48     7.90        2.90    17.20

                 2000            5       1,012.04   4.94        1.60    11.53

                 2001            9       1,397.41   6.44        2.94    12.23

                 2002            2       226.66     8.82        1.07    31.88

  6-7 yrs        1995            .       1.13       .           .       .

                 1996            2       121.12     16.51       2.00    59.65

                 1997            2       509.52     3.93        0.47    14.18

                 1998            1       713.63     1.40        0.04    7.81

                 1999            6       732.03     8.20        3.01    17.84

                 2000            4       753.58     5.31        1.45    13.59

                 2001            7       1,007.17   6.95        2.79    14.32

                 2002            1       204.06     4.90        0.12    27.31

  7-8 yrs        1996            .       1.22       .           .       .

                 1997            2       120.02     16.66       2.02    60.20

                 1998            .       506.01     .           .       .

                 1999            3       706.52     4.25        0.88    12.41

                 2000            4       733.75     5.45        1.49    13.96

                 2001            2       747.44     2.68        0.32    9.67

                 2002            .       147.97     .           .       .

  8-9 yrs        1997            .       1.28       .           .       .

                 1998            .       118.35     .           .       .

                 1999            3       512.29     5.86        1.21    17.11

                 2000            6       705.50     8.50        3.12    18.51

                 2001            3       734.61     4.08        0.84    11.93

                 2002            .       111.43     .           .       .

  9-10 yrs       1998            .       1.03       .           .       .

                 1999            .       118.15     .           .       .

                 2000            2       508.27     3.93        0.48    14.21

                 2001            2       707.49     2.83        0.34    10.21

                 2002            .       115.89     .           .       .

  \>10 yrs       1999            .       1.03       .           .       .

                 2000            1       120.42     8.30        0.21    46.27

                 2001            3       626.86     4.79        0.99    13.99

                 2002            1       171.69     5.82        0.15    32.45
  ------------------------------------------------------------------------------

#  

# 16 Red alert incidence per 1,000 person-years and 95% CI, by treatment duration and monitoring frequency, in the UK CPMS.

  ---------------------------------------------------------------------------
  **Table 4.16.                                                      
  Red alert                                                          
  incidence per                                                      
  1,000                                                              
  person-years                                                       
  and 95% CI, by                                                     
  treatment                                                          
  duration and                                                       
  monitoring                                                         
  frequency, in                                                      
  the UK CPMS.**                                                     
  --------------- --------- ------- ----------- ----------- -------- --------
                            Cases   Pat-yrs     Incidence   95%      CI

  Trt duration    Monitor   658     7,575.17    86.86       80.23    93.50

  0-18 wks        1W                                                 

  19-52 wks       1W        223     2,506.63    88.96       77.29    100.64

                  2W        33      8,616.53    3.83        2.52     5.14

  +52 wks         1W        309     2,518.03    122.71      109.03   136.40

                  2W        40      10,978.36   3.64        2.51     4.77

                  4W        71      43,181.76   1.64        1.26     2.03
  ---------------------------------------------------------------------------

1W - patients who were monitored weekly

2W - patients who were monitored every two weeks

4W - patients who were monitored every four weeks (monthly)

# 17 Red alert incidence per 1,000 person-years and 95% CI, by calendar year (2-year intervals), treatment duration and monitoring frequency, in the UK CPMS.

  ----------------------------------------------------------------------------------------
  **Table 4.17.                                                                   
  Red alert                                                                       
  incidence per                                                                   
  1,000                                                                           
  person-years                                                                    
  and 95% CI, by                                                                  
  calendar year                                                                   
  (2-year                                                                         
  intervals),                                                                     
  treatment                                                                       
  duration and                                                                    
  monitoring                                                                      
  frequency, in                                                                   
  the UK CPMS.**                                                                  
  -------------- --------- ------------- ------- ----------- ----------- -------- --------
                                         Cases   Pat-yrs     Incidence   95%      CI

  Trt duration   monitor   Calendar year 61      524.90      116.21      87.05    145.38

  0-18 wks       1W        1990-1991                                              

                           1992-1993     88      836.64      105.18      83.21    127.16

                           1994-1995     100     1,022.03    97.84       78.67    117.02

                           1996-1997     98      1,339.29    73.17       58.69    87.66

                           1998-1999     161     1,710.74    94.11       79.57    108.65

                           2000-2002\*   150     2,141.58    70.04       58.83    81.25

  19-52 wks      1W        1990-1991     13      115.98      112.09      59.68    191.67

                           1992-1993     43      295.12      145.70      102.15   189.25

                           1994-1995     26      315.53      82.40       50.73    114.07

                           1996-1997     33      472.24      69.88       46.04    93.72

                           1998-1999     54      577.84      93.45       68.53    118.38

                           2000-2002\*   54      729.92      73.98       54.25    93.71

                 2W        1990-1991     3       314.03      9.55        1.97     27.92

                           1992-1993     4       995.66      4.02        1.09     10.28

                           1994-1995     1       1,064.82    0.94        0.02     5.23

                           1996-1997     8       1,677.30    4.77        2.06     9.40

                           1998-1999     8       1,884.78    4.24        1.83     8.36

                           2000-2002\*   9       2,679.93    3.36        1.54     6.38

  +52 wks        1W        1990-1991     1       13.73       72.83       1.82     405.82

                           1992-1993     27      207.76      129.96      80.94    178.98

                           1994-1995     34      346.71      98.06       65.10    131.03

                           1996-1997     51      434.40      117.40      85.18    149.63

                           1998-1999     73      646.84      112.86      86.97    138.75

                           2000-2002\*   123     868.59      141.61      116.58   166.63

                 2W        1990-1991     1       128.91      7.76        0.19     43.22

                           1992-1993     6       2,107.50    2.85        1.04     6.20

                           1994-1995     14      3,828.73    3.66        2.00     6.14

                           1996-1997     4       1,524.43    2.62        0.72     6.72

                           1998-1999     6       1,594.00    3.76        1.38     8.19

                           2000-2002\*   9       1,794.79    5.01        2.29     9.52

                 4W        1994-1995     1       1,128.30    0.89        0.02     4.94

                           1996-1997     9       7,795.15    1.15        0.53     2.19

                           1998-1999     22      12,586.90   1.75        1.02     2.48

                           2000-2002\*   39      21,671.41   1.80        1.23     2.36
  ----------------------------------------------------------------------------------------

1W - patients who were monitored weekly

2W - patients who were monitored every two weeks

4W - patients who were monitored every four weeks (monthly)

# 18 Red alert incidence per 1,000 person-years and 95% CI, by treatment duration and cohort in the UK CPMS.

  ----------------------------------------------------------------------------------
  **Table 4.18.                                                             
  Red incidence                                                             
  per 1,000                                                                 
  person-years                                                              
  and 95% CI, by                                                            
  treatment                                                                 
  duration and                                                              
  cohort in the                                                             
  UK CPMS.**                                                                
  -------------- ------------------ ------- ----------- ----------- ------- --------
                                    Cases   Pat-yrs     Incidence   95%     CI

  Trt duration   Cohort             182     1,731.75    105.10      89.83   120.36

  0-18 wks       Initial system                                             

                 Current system,    482     5,839.83    82.54       75.17   89.91
                 new patients                                               

                 Current system,    .       1.20        .           .       .
                 old patients                                               

  19-52 wks      Initial system     79      2,586.62    30.54       23.81   37.28

                 Current system,    177     8,552.11    20.70       17.65   23.75
                 new patients                                               

                 Current system,    .       3.14        .           .       .
                 old patients                                               

  +52 wks        Initial system     77      6,542.55    11.77       9.14    14.40

                 Current system,    228     30,693.75   7.43        6.46    8.39
                 new patients                                               

                 Current system,    113     19,499.30   5.80        4.73    6.86
                 old patients                                               
  ----------------------------------------------------------------------------------

# 19 Red alert incidence per 1,000 person-years and 95% CI, by treatment duration, monitoring frequency and cohort in the UK CPMS.

  --------------------------------------------------------------------------------------
  **Table 4.19.                                                                 
  Red incidence                                                                 
  per 1,000                                                                     
  person-years                                                                  
  and 95% CI, by                                                                
  treatment                                                                     
  duration,                                                                     
  monitoring                                                                    
  frequency and                                                                 
  cohort in the                                                                 
  UK CPMS.**                                                                    
  -------------- --------- ----------- ------- ----------- ----------- -------- --------
                                       Cases   Pat-yrs     Incidence   95%      CI

  Trt duration   monitor   Cohort      180     1,730.38    104.02      88.83    119.22

  0-18 wks       1W        Initial                                              
                           system                                               

                           Current     478     5,836.92    81.89       74.55    89.23
                           system, new                                          
                           patients                                             

                           Current     .       1.20        .           .        .
                           system, old                                          
                           patients                                             

  19-52 wks      1W        Initial     72      576.70      124.85      96.01    153.69
                           system                                               

                           Current     151     1,927.84    78.33       65.83    90.82
                           system, new                                          
                           patients                                             

                           Current     .       0.79        .           .        .
                           system, old                                          
                           patients                                             

                 2W        Initial     7       2,004.42    3.49        1.40     7.19
                           system                                               

                           Current     26      6,605.80    3.94        2.42     5.45
                           system, new                                          
                           patients                                             

                           Current     .       2.05        .           .        .
                           system, old                                          
                           patients                                             

  +52 wks        1W        Initial     57      492.97      115.62      85.61    145.64
                           system                                               

                           Current     170     1,303.73    130.39      110.79   150.00
                           system, new                                          
                           patients                                             

                           Current     80      718.72      111.31      86.92    135.70
                           system, old                                          
                           patients                                             

                 2W        Initial     20      6,038.57    3.31        2.02     5.12
                           system                                               

                           Current     14      3,310.65    4.23        2.31     7.10
                           system, new                                          
                           patients                                             

                           Current     6       1,625.35    3.69        1.35     8.04
                           system, old                                          
                           patients                                             

                 4W        Current     44      26,034.87   1.69        1.19     2.19
                           system, new                                          
                           patients                                             

                           Current     26      17,131.16   1.52        0.93     2.10
                           system, old                                          
                           patients                                             
  --------------------------------------------------------------------------------------

1W - patients who were monitored weekly

2W - patients who were monitored every two weeks

4W - patients who were monitored every four weeks (monthly)

# 20 Red alert treatment withdrawal criteria, in the UK CPMS

###### 

  -----------------------------------------------------------------------
  **Table 4.20. Red alert treatment                 
  withdrawal criteria, in the UK                    
  CPMS.**                                           
  --------------------------------- --------------- ---------------------
  Criteria                          n               \%

  Agran                             215             16.03

  Neutropenia                       762             56.82

  Other                             215             16.03

  Leucopenia                        149             11.11
  -----------------------------------------------------------------------

# 21 Demographic characteristics of the UK CPMS patients included in the analysis, by cohort.

  ---------------------------------------------------------------------------------------
  **Table 4.21.                                                                   
  Demographic                                                                     
  characteristics                                                                 
  of the UK CPMS                                                                  
  patients included                                                               
  in the analysis,                                                                
  by cohort.**                                                                    
  ----------------- ------- ------- -------- ------- --------- ------- ---------- -------
                    All             Cohort                                        

                                    .                Initial           Current    
                                                     system            system,    
                                                                       new        
                                                                       patients   

                    n       \%      n        \%      n         \%      n          \%

  Sex               9077    32.54   13       28.26   2174      34.10   6890       32.09

  F                                                                               

  M                 18817   67.46   33       71.74   4201      65.90   14583      67.91

  Age groups        14483   51.92   27       58.70   3220      50.51   11236      52.33

  \<=35                                                                           

  36-50             9273    33.24   12       26.09   2208      34.64   7053       32.85

  51-65             3400    12.19   6        13.04   767       12.03   2627       12.23

  \>65              738     2.65    1        2.17    180       2.82    557        2.59

  Race              1669    5.98    2        4.35    278       4.36    1389       6.47

  AFRO-CARIB                                                                      

  ASIAN             1206    4.32    3        6.52    206       3.23    997        4.64

  CAUCASIAN         24444   87.63   37       80.43   5755      90.27   18652      86.86

  MIXED             460     1.65    3        6.52    112       1.76    345        1.61

  ORIENTAL          115     0.41    1        2.17    24        0.38    90         0.42
  ---------------------------------------------------------------------------------------

# 22 Demographic characteristics of the UK CPMS patients with agranulocytosis , by cohort.

  ----------------------------------------------------------------------------------------
  **Table 4.22.                                                                   
  Demographic                                                                     
  characteristics                                                                 
  of the UK CPMS                                                                  
  patients with                                                                   
  agranulocytosis ,                                                               
  by cohort.**                                                                    
  ----------------- ----- ------- --------- ------- ---------- ------- ---------- --------
                    All           Cohort                                          

                                  Initial           Current            Current    
                                  system            system,            system,    
                                                    new                old        
                                                    patients           patients   

                    n     \%      n         \%      n          \%      n          \%

  Sex               85    38.99   20        41.67   58         38.67   7          35.00

  F                                                                               

  M                 133   61.01   28        58.33   92         61.33   13         65.00

  Age groups        52    23.85   12        25.00   35         23.33   5          25.00

  \<=35                                                                           

  36-50             91    41.74   25        52.08   54         36.00   12         60.00

  51-65             66    30.28   11        22.92   52         34.67   3          15.00

  \>65              9     4.13    .         .       9          6.00    .          .

  Race              3     1.38    1         2.08    1          0.67    1          5.00

  AFRO-CARIB                                                                      

  ASIAN             11    5.05    2         4.17    9          6.00    .          .

  CAUCASIAN         202   92.66   45        93.75   138        92.00   19         95.00

  MIXED             2     0.92    .         .       2          1.33    .          .
  ----------------------------------------------------------------------------------------

# 23 Demographic characteristics of the UK CPMS patients with severe leukopenia, by cohort.

  ---------------------------------------------------------------------------------------------------------
  **Table 4.23.                                                                                     
  Demographic                                                                                       
  characteristics                                                                                   
  of the UK CPMS                                                                                    
  patients with                                                                                     
  severe                                                                                            
  leukopenia, by                                                                                    
  cohort.**                                                                                         
  ----------------- ----- ------- -------- -------- --------- ------- ---------- ------- ---------- -------
                    All           Cohort                                                            

                                  .                 Initial           Current            Current    
                                                    system            system,            system,    
                                                                      new                old        
                                                                      patients           patients   

                    n     \%      n        \%       n         \%      n          \%      n          \%

  Sex               153   38.25   2        100.00   34        39.53   105        37.77   12         35.29

  F                                                                                                 

  M                 247   61.75   .        .        52        60.47   173        62.23   22         64.71

  Age groups        126   31.50   1        50.00    27        31.40   86         30.94   12         35.29

  \<=35                                                                                             

  36-50             158   39.50   .        .        40        46.51   101        36.33   17         50.00

  51-65             101   25.25   .        .        19        22.09   77         27.70   5          14.71

  \>65              15    3.75    1        50.00    .         .       14         5.04    .          .

  Race              22    5.50    .        .        4         4.65    17         6.12    1          2.94

  AFRO-CARIB                                                                                        

  ASIAN             21    5.25    .        .        4         4.65    16         5.76    1          2.94

  CAUCASIAN         353   88.25   .        .        78        90.70   243        87.41   32         94.12

  MIXED             4     1.00    2        100.00   .         .       2          0.72    .          .
  ---------------------------------------------------------------------------------------------------------

# 24 Demographic characteristics of the UK CPMS patients with red alert, by cohort.

  ----------------------------------------------------------------------------------------------------------
  **Table 4.24.                                                                                      
  Demographic                                                                                        
  characteristics                                                                                    
  of the UK CPMS                                                                                     
  patients with red                                                                                  
  alert, by                                                                                          
  cohort.**                                                                                          
  ----------------- ------ ------- -------- -------- --------- ------- ---------- ------- ---------- -------
                    All            Cohort                                                            

                                   .                 Initial           Current            Current    
                                                     system            system,            system,    
                                                                       new                old        
                                                                       patients           patients   

                    n      \%      n        \%       n         \%      n          \%      n          \%

  Sex               528    39.34   3        100.00   136       40.24   348        39.23   41         35.96

  F                                                                                                  

  M                 814    60.66   .        .        202       59.76   539        60.77   73         64.04

  Age groups        645    48.06   1        33.33    173       51.18   419        47.24   52         45.61

  \<=35                                                                                              

  36-50             433    32.27   1        33.33    109       32.25   274        30.89   49         42.98

  51-65             226    16.84   .        .        53        15.68   161        18.15   12         10.53

  \>65              38     2.83    1        33.33    3         0.89    33         3.72    1          0.88

  Race              160    11.92   .        .        28        8.28    126        14.21   6          5.26

  AFRO-CARIB                                                                                         

  ASIAN             53     3.95    .        .        8         2.37    38         4.28    7          6.14

  CAUCASIAN         1108   82.56   1        33.33    297       87.87   711        80.16   99         86.84

  MIXED             19     1.42    2        66.67    5         1.48    11         1.24    1          0.88

  ORIENTAL          2      0.15    .        .        .         .       1          0.11    1          0.88
  ----------------------------------------------------------------------------------------------------------

#  Figures 

#  Agranulocytosis incidence per 1,000 person years and 95% CI, for the first 84 weeks of treatment (in 2-week intervals).

![](media/image1.wmf){width="6.3in" height="4.327083333333333in"}

#  Agranulocytosis incidence per 1,000 person years and 95% CI, by treatment duration (in 6-week intervals).

![](media/image2.wmf){width="6.3in" height="4.301388888888889in"}

#  Severe leukopenia incidence per 1,000 person years and 95% CI, for the first 84 weeks of treatment (in 2-week intervals).

![](media/image3.wmf){width="6.3in" height="4.295138888888889in"}

#  Severe leukopenia incidence per 1,000 person years and 95% CI, by treatment duration (in 6-week intervals).

![](media/image4.wmf){width="6.3in" height="4.256944444444445in"}

#  Red alert incidence per 1,000 person years and 95% CI, for the first 84 weeks of treatment (in 2-week intervals). 

![](media/image5.wmf){width="6.3in" height="4.256944444444445in"}

#  Red alert incidence per 1,000 person years and 95% CI, by treatment duration (in 6-week intervals). 

![](media/image6.wmf){width="6.3in" height="4.339583333333334in"}