Lowering your handicap with Stata
Tim Collier
Medical Statistics Department,
LSHTM
&
Leaside Golf Club, Edmonton
The Inception
The Inception
Stata
Golf
Time
Stata
Golf
Spare
Time
Stata
Golf
Spare
Time
Stata
Golf
Data Monitoring for Clinical Trials
•
Double blind Randomised Controlled Trial
•
New drug/treatment versus a control
•
•
•
Previously tested in a small number of healthy
volunteers or specially selected patients
DSMB – committee of independent clinical
experts and a statistician
Regularly produce routine reports – safety and
Typical Data Monitoring Report
•
Baseline summary
•
Recruitment and Patient status
•
Adherence
•
Safety – adverse events
•
Efficacy – primary & secondary endpoints
•
Concomitant medications
•
Laboratory values, vital signs
Typical Data Monitoring Report
•
Stata programming can save vast amounts
of time particularly when repeating
analyses and production of routine reports
Demonstration
The following tables were all produced
directly from Stata using relatively simple
user written Stata programs
Adverse Event Table 1
————————————————————————————————————————————————————————————————————————————————————————————————
Table 1.1: SERIOUS ADVERSE EVENTS
Group A
Group B
—————————————————————
—————————————————————
System Organ Class
NP (%)
NE
NP (%)
NE
————————————————————————————————————————————————————————————————————————————————————————————————
Blood and lymphatic system disorders
34 (0.4)
35
32 (0.3)
32
Cardiac disorders
312 (3.3)
353
324 (3.4)
384
Congenital, familial and genetic disorders
13 (0.1)
13
13 (0.1)
13
Ear and labyrinth disorders
52 (0.5)
53
57 (0.6)
58
Endocrine disorders
9 (0.1)
9
7 (0.1)
7
Eye disorders
44 (0.5)
49
51 (0.5)
58
Gastrointestinal disorders
202 (2.1)
216
221 (2.3)
236
General disorders and administration site
conditions
134 (1.4)
134
128 (1.3)
132
Hepatobiliary disorders
48 (0.5)
52
51 (0.5)
55
Immune system disorders
9 (0.1)
9
8 (0.1)
8
Infections and infestations
373 (3.9)
443
343 (3.6)
404
Injury, poisoning and procedural complications
232 (2.4)
246
225 (2.4)
239
Investigations
29 (0.3)
31
39 (0.4)
41
Metabolism and nutrition disorders
83 (0.9)
88
98 (1.0)
104
Musculoskeletal and connective tissue disorders
128 (1.3)
145
173 (1.8)
177
**
Neoplasms benign, malignant and unspecified
(incl cysts and polyps)
171 (1.8)
175
167 (1.8)
171
Nervous system disorders
317 (3.3)
356
279 (2.9)
305
Psychiatric disorders
44 (0.5)
48
66 (0.7)
70
*
Renal and urinary disorders
76 (0.8)
78
58 (0.6)
60
Reproductive system and breast disorders
17 (0.2)
17
20 (0.2)
20
Respiratory, thoracic and mediastinal disorders
124 (1.3)
148
119 (1.3)
137
Skin and subcutaneous tissue disorders
10 (0.1)
11
11 (0.1)
11
Surgical and medical procedures
53 (0.6)
55
49 (0.5)
52
Vascular disorders
170 (1.8)
187
217 (2.3)
232
*
————————————————————————————————————————————————————————————————————————————————————————————————
NP:nos of patients with 1+ events; NE: nos of events; * = p<0.05, ** = p<0.01 and *** = p<0.001
Adverse Event Table 2
——————————————————————————————————————————————————————————————————————————————————————————————————
Table 1.2: SERIOUS ADVERSE EVENTS
Group A
Group B
——————————————————————— ———————————————————————
System Organ Class
NP (%)
NE Fatal
NP (%)
NE Fatal
——————————————————————————————————————————————————————————————————————————————————————————————————
Blood and lymphatic system disorders
34 (0.4)
35
1
32 (0.3)
32
1
Cardiac disorders
312 (3.3)
353 11
324 (3.4)
384 10
Congenital, familial and genetic disorders
13 (0.1)
13
0
13 (0.1)
13
0
Ear and labyrinth disorders
52 (0.5)
53
0
57 (0.6)
58
0
Endocrine disorders
9 (0.1)
9
0
7 (0.1)
7
0
Eye disorders
44 (0.5)
49
0
51 (0.5)
58
0
Gastrointestinal disorders
202 (2.1)
216
5
221 (2.3)
236
4
General disorders and administration site
conditions
134 (1.4)
134 84
128 (1.3)
132 84
Hepatobiliary disorders
48 (0.5)
52
2
51 (0.5)
55
0
Immune system disorders
9 (0.1)
9
0
8 (0.1)
8
0
Infections and infestations
373 (3.9)
443 39
343 (3.6)
404 56
Injury, poisoning and procedural complications
232 (2.4)
246
6
225 (2.4)
239
4
Investigations
29 (0.3)
31
0
39 (0.4)
41
0
Metabolism and nutrition disorders
83 (0.9)
88
0
98 (1.0)
104
2
Musculoskeletal and connective tissue disorders
128 (1.3)
145
0
173 (1.8)
177
0 **
Neoplasms benign, malignant and unspecified
(incl cysts and polyps)
171 (1.8)
175 35
167 (1.8)
171 40
Nervous system disorders
317 (3.3)
356
4
279 (2.9)
305
1
Psychiatric disorders
44 (0.5)
48
4
66 (0.7)
70
8 *
Renal and urinary disorders
76 (0.8)
78
1
58 (0.6)
60
2
Reproductive system and breast disorders
17 (0.2)
17
0
20 (0.2)
20
0
Respiratory, thoracic and mediastinal disorders
124 (1.3)
148 25
119 (1.3)
137 21
Skin and subcutaneous tissue disorders
10 (0.1)
11
0
11 (0.1)
11
1
Surgical and medical procedures
53 (0.6)
55
0
49 (0.5)
52
0
Vascular disorders
170 (1.8)
187
1
217 (2.3)
232
0 *
——————————————————————————————————————————————————————————————————————————————————————————————————
NP:nos of patients with 1+ events; NE: nos of events; * = p<0.05, ** = p<0.01 and *** = p<0.001
Fatal - nos of events with outcome recorded as fatal
Adverse Event Table Two levels 3 (edited)
————————————————————————————————————————————————————————————————————————————————————————————————
Table 1.5: SERIOUS ADVERSE EVENTS
Group A
Group B
—————————————————————
—————————————————————
System Organ Class/MedDRA Preferred term
NP (%)
NE
NP (%)
NE
————————————————————————————————————————————————————————————————————————————————————————————————
BLOOD AND LYMPHATIC SYSTEM DISORDERS
34 (0.4)
35
32 (0.3)
32
––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
Anaemia
20 (0.2)
21
15 (0.2)
15
Iron deficiency anaemia
7 (0.1)
7
7 (0.1)
7
Microcytic anaemia
5 (0.1)
5
1 (<0.1)
1
Thrombocytopenia
2 (<0.1)
2
9 (0.1)
9
*
––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
CARDIAC DISORDERS
312 (3.3)
353
324 (3.4)
384
––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
Angina pectoris
26 (0.3)
26
30 (0.3)
32
EDITED
EDITED
––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
EAR AND LABYRINTH DISORDERS
52 (0.5)
53
57 (0.6)
58
––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
Acute vestibular syndrome
6 (0.1)
7
5 (0.1)
5
Vertigo
21 (0.2)
21
19 (0.2)
19
Vertigo positional
8 (0.1)
8
17 (0.2)
17
Vestibular disorder
10 (0.1)
10
13 (0.1)
13
Vestibular neuronitis
7 (0.1)
7
4 (<0.1)
4
––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
ENDOCRINE DISORDERS
9 (0.1)
9
7 (0.1)
7
––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
Goitre
7 (0.1)
7
5 (0.1)
5
Hyperthyroidism
2 (<0.1)
2
2 (<0.1)
2
––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
EYE DISORDERS
44 (0.5)
49
51 (0.5)
58
––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
Cataract
38 (0.4)
42
43 (0.5)
49
————————————————————————————————————————————————————————————————————————————————————————————————
NP:nos of patients with 1+ events; N: nos of events; * = p<0.05, ** = p<0.01 and *** = p<0.001
Adverse Event Table Two levels 3 (edited)
————————————————————————————————————————————————————————————————————————————————————————————————
Table 1.5: SERIOUS ADVERSE EVENTS
Group A
Group B
—————————————————————
—————————————————————
System Organ Class/MedDRA Preferred term
NP (%)
NE
NP (%)
NE
————————————————————————————————————————————————————————————————————————————————————————————————
EYE DISORDERS (contd)
Diabetic retinopathy
2 (<0.1)
2
3 (<0.1)
3
Retinal detachment
5 (0.1)
5
6 (0.1)
6
––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
GASTROINTESTINAL DISORDERS
202 (2.1)
216
221 (2.3)
236
––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
Abdominal hernia
2 (<0.1)
2
4 (<0.1)
4
Abdominal pain
5 (0.1)
5
4 (<0.1)
4
Anal fissure
4 (<0.1)
4
1 (<0.1)
1
EDITED
EDITED
––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
GENERAL DISORDERS AND ADMINISTRATION SITE
CONDITIONS
134 (1.4)
134
128 (1.3)
132
––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
Chest pain
24 (0.3)
24
20 (0.2)
21
Death
49 (0.5)
49
41 (0.4)
41
Drug intolerance
5 (0.1)
5
3 (<0.1)
3
Gait disturbance
5 (0.1)
5
2 (<0.1)
2
General physical health deterioration
11 (0.1)
11
7 (0.1)
7
Malaise
2 (<0.1)
2
3 (<0.1)
3
Non-cardiac chest pain
4 (<0.1)
4
4 (<0.1)
4
Oedema peripheral
1 (<0.1)
1
4 (<0.1)
4
Pyrexia
3 (<0.1)
3
5 (0.1)
7
Sudden death
30 (0.3)
30
40 (0.4)
40
––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
HEPATOBILIARY DISORDERS
48 (0.5)
52
51 (0.5)
55
––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
Bile duct stone
2 (<0.1)
2
6 (0.1)
6
————————————————————————————————————————————————————————————————————————————————————————————————
NP:nos of patients with 1+ events; N: nos of events; * = p<0.05, ** = p<0.01 and *** = p<0.001
Baseline Demographic Table (edited)
————————————————————————————————————————————————————————————————————————————————
Table 1:1 Baseline Demographics
Group A
Group B
(N=485)
(N=492)
————————————————————————————————————————————————————————————————————————————————
GENDER-Nos.(%)
————————————————————————————————————————————————————————————————————————————————
Male
264 (54.5)
271 (55.3)
Female
220 (45.5)
219 (44.7)
Missing
1
2
————————————————————————————————————————————————————————————————————————————————
AGE AT RANDOMISATION (yrs)
————————————————————————————————————————————————————————————————————————————————
Number
484
490
Mean (SD)
59.4 (10.6)
59.7 (10.9)
Median (IQR)
59.7 (52.7 to 67.3) 60.5 (51.8 to 67.6)
Range
23.5 to 83.7
29.0 to 86.6
AGE CATEGORIES-Nos.(%)
18-49 yrs
50-59 yrs
60-69 yrs
70+ yrs
89
156
156
83
(18.4)
(32.2)
(32.2)
(17.1)
91
145
166
88
(18.6)
(29.6)
(33.9)
(18.0)
Missing
1
2
————————————————————————————————————————————————————————————————————————————————
DURATION OF DIABETES (yrs)
————————————————————————————————————————————————————————————————————————————————
Number
483
488
Median (IQR)
8.8 (4.3 to 13.7)
9.2 (4.9 to 13.8)
Range
0.1 to 42.5
0.2 to 63.2
Missing
2
5
————————————————————————————————————————————————————————————————————————————————
SAE event listing (edited)
————————————————————————————————————————————————————————————————————————————————
Patient number:
XXX-XXX
————————————————————————————————————————————————————————————————————————————————
Age/Gender:
82 years/Female
Treatment group:
Group F
Date of Randomisation:
16/Aug/2011
Date of SAE Onset:
23/Aug/2011
Date of SAE stop:
25/Aug/2011
SAE Narrative:
Subject presented to the ER c/o intractable nausea and abdominal pain on 23Aug20
11. CT scan identified left ovarian thrombus. On 24Aug2011 the patient reported
that the abdominal pain had intensified. On the 26Aug2011 the patient experienced
a
SAE Treatment:
Doctor requested much longer string variables
SAE Outcome:
Recovered
SAE Criteria:
Hospitalization
Relation to study drug:
Definitely not related to study drug
Action with Study Drug:
None
SAR Severity:
Moderate
————————————————————————————————————————————————————————————————————————————————