Lowering your handicap with Stata

Tim Collier

Medical Statistics Department, LSHTM

& Leaside Golf Club, Edmonton

The Inception

The Inception

GolfStata

GolfStata

Time

GolfStata

Spare Time

GolfStata

Spare Time

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 efficacy

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

————————————————————————————————————————————————————————————————————————————————————————————————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 1

——————————————————————————————————————————————————————————————————————————————————————————————————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<0.001Fatal - nos of events with outcome recorded as fatal

Adverse Event Table 2

————————————————————————————————————————————————————————————————————————————————————————————————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

Adverse Event Table Two levels 3 (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 89 (18.4) 91 (18.6) 50-59 yrs 156 (32.2) 145 (29.6) 60-69 yrs 156 (32.2) 166 (33.9) 70+ yrs 83 (17.1) 88 (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————————————————————————————————————————————————————————————————————————————————

Baseline Demographic Table (edited)

————————————————————————————————————————————————————————————————————————————————Patient number: XXX-XXX————————————————————————————————————————————————————————————————————————————————Age/Gender: 82 years/FemaleTreatment group: Group FDate of Randomisation: 16/Aug/2011Date of SAE Onset: 23/Aug/2011Date of SAE stop: 25/Aug/2011

SAE Narrative:Subject presented to the ER c/o intractable nausea and abdominal pain on 23Aug2011. CT scan identified left ovarian thrombus. On 24Aug2011 the patient reported that the abdominal pain had intensified. On the 26Aug2011 the patient experienceda

SAE Treatment:Doctor requested much longer string variables

SAE Outcome: RecoveredSAE Criteria: HospitalizationRelation to study drug: Definitely not related to study drugAction with Study Drug: NoneSAR Severity: Moderate————————————————————————————————————————————————————————————————————————————————

SAE event listing (edited)