Lowering your handicap with Stata Tim Collier Medical Statistics Department, LSHTM & Leaside Golf Club, Edmonton

The Inception

Golf Stata

Golf Stata Time

Golf Stata Spare Time

Golf Stata 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) (0.3) 32 Cardiac disorders 312 (3.3) (3.4) 384 Congenital, familial and genetic disorders 13 (0.1) (0.1) 13 Ear and labyrinth disorders 52 (0.5) (0.6) 58 Endocrine disorders 9 (0.1) 9 7 (0.1) 7 Eye disorders 44 (0.5) (0.5) 58 Gastrointestinal disorders 202 (2.1) (2.3) 236 General disorders and administration site conditions 134 (1.4) (1.3) 132 Hepatobiliary disorders 48 (0.5) (0.5) 55 Immune system disorders 9 (0.1) 9 8 (0.1) 8 Infections and infestations 373 (3.9) (3.6) 404 Injury, poisoning and procedural complications 232 (2.4) (2.4) 239 Investigations 29 (0.3) (0.4) 41 Metabolism and nutrition disorders 83 (0.9) (1.0) 104 Musculoskeletal and connective tissue disorders 128 (1.3) (1.8) 177 ** Neoplasms benign, malignant and unspecified (incl cysts and polyps) 171 (1.8) (1.8) 171 Nervous system disorders 317 (3.3) (2.9) 305 Psychiatric disorders 44 (0.5) (0.7) 70 * Renal and urinary disorders 76 (0.8) (0.6) 60 Reproductive system and breast disorders 17 (0.2) (0.2) 20 Respiratory, thoracic and mediastinal disorders 124 (1.3) (1.3) 137 Skin and subcutaneous tissue disorders 10 (0.1) (0.1) 11 Surgical and medical procedures 53 (0.6) (0.5) 52 Vascular disorders 170 (1.8) (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) (0.3) 32 1 Cardiac disorders 312 (3.3) (3.4) Congenital, familial and genetic disorders 13 (0.1) (0.1) 13 0 Ear and labyrinth disorders 52 (0.5) (0.6) 58 0 Endocrine disorders 9 (0.1) (0.1) 7 0 Eye disorders 44 (0.5) (0.5) 58 0 Gastrointestinal disorders 202 (2.1) (2.3) General disorders and administration site conditions 134 (1.4) (1.3) Hepatobiliary disorders 48 (0.5) (0.5) 55 0 Immune system disorders 9 (0.1) (0.1) 8 0 Infections and infestations 373 (3.9) (3.6) Injury, poisoning and procedural complications 232 (2.4) (2.4) Investigations 29 (0.3) (0.4) 41 0 Metabolism and nutrition disorders 83 (0.9) (1.0) Musculoskeletal and connective tissue disorders 128 (1.3) (1.8) ** Neoplasms benign, malignant and unspecified (incl cysts and polyps) 171 (1.8) (1.8) Nervous system disorders 317 (3.3) (2.9) Psychiatric disorders 44 (0.5) (0.7) 70 8 * Renal and urinary disorders 76 (0.8) (0.6) 60 2 Reproductive system and breast disorders 17 (0.2) (0.2) 20 0 Respiratory, thoracic and mediastinal disorders 124 (1.3) (1.3) Skin and subcutaneous tissue disorders 10 (0.1) (0.1) 11 1 Surgical and medical procedures 53 (0.6) (0.5) 52 0 Vascular disorders 170 (1.8) (2.3) * —————————————————————————————————————————————————————————————————————————————————————————————————— 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 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) (0.3) 32 –––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– Anaemia 20 (0.2) (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) (3.4) 384 –––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– Angina pectoris 26 (0.3) (0.3) 32 EDITED EDITED –––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– EAR AND LABYRINTH DISORDERS 52 (0.5) (0.6) 58 –––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– Acute vestibular syndrome 6 (0.1) 7 5 (0.1) 5 Vertigo 21 (0.2) (0.2) 19 Vertigo positional 8 (0.1) 8 17 (0.2) 17 Vestibular disorder 10 (0.1) (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) (0.5) 58 –––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– Cataract 38 (0.4) (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) (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 –––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 134 (1.4) (1.3) 132 –––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– Chest pain 24 (0.3) (0.2) 21 Death 49 (0.5) (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) (0.4) 40 –––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– HEPATOBILIARY DISORDERS 48 (0.5) (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 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 to 86.6 AGE CATEGORIES-Nos.(%) yrs 89 (18.4) 91 (18.6) yrs 156 (32.2) 145 (29.6) yrs 156 (32.2) 166 (33.9) 70+ yrs 83 (17.1) 88 (18.0) Missing 1 2 ———————————————————————————————————————————————————————————————————————————————— DURATION OF DIABETES (yrs) ———————————————————————————————————————————————————————————————————————————————— Number Median (IQR) 8.8 (4.3 to 13.7) 9.2 (4.9 to 13.8) Range 0.1 to to 63.2 Missing 2 5 ———————————————————————————————————————————————————————————————————————————————— Baseline Demographic Table (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 23Aug 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 ———————————————————————————————————————————————————————————————————————————————— SAE event listing (edited)