Adverse Events
Introduction
This guide will show you how pharmaverse packages, along with some from tidyverse, can be used to create an Adverse Events table, using the {pharmaverseadam} ADSL and ADAE data as an input. ## Multiple Approaches Shown
This example includes:
- ARD-based approach:
{cards}+{tfrmt}- Creates structured Analysis Results Datasets following CDISC standards, then formats them into tables - Classic approach:
{rtables}+{tern}- Direct table creation from datasets using mature, stable packages
In the examples below, we illustrate two general approaches for creating an Adverse events table. The first is the classic method of creating summary tables directly from a data set. The second utilizes Analysis Results Datasets—part of the emerging CDISC Analysis Results Standard.
{rtables} & {tern}
The packages used with a brief description of their purpose are as follows:
{rtables}: designed to create and display complex tables with R.{tern}: contains analysis functions to create tables and graphs used for clinical trial reporting.
Load Data and Required pharmaverse Package
After installation of packages, the first step is to load our pharmaverse packages and input data. Here, we are going to encode missing entries in a data frame adsl and adae.
Note that {tern} depends on {rtables} so the latter is automatically attached.
Start preprocessing
Now we will add some pre-processing to add labels ready for display in the table and how the output will be split.
Adverse Events table
Now we create the Adverse Events table.
lyt <- basic_table(show_colcounts = TRUE) %>%
split_cols_by(var = "ACTARM") %>%
add_overall_col(label = "All Patients") %>%
analyze_num_patients(
vars = "USUBJID",
.stats = c("unique", "nonunique"),
.labels = c(
unique = "Total number of patients with at least one adverse event",
nonunique = "Overall total number of events"
)
) %>%
split_rows_by(
"AEBODSYS",
child_labels = "visible",
nested = FALSE,
split_fun = split_fun,
label_pos = "topleft",
split_label = obj_label(adae$AEBODSYS)
) %>%
summarize_num_patients(
var = "USUBJID",
.stats = c("unique", "nonunique"),
.labels = c(
unique = "Total number of patients with at least one adverse event",
nonunique = "Total number of events"
)
) %>%
count_occurrences(
vars = "AEDECOD",
.indent_mods = -1L
) %>%
append_varlabels(adae, "AEDECOD", indent = 1L)
result <- build_table(lyt, df = adae, alt_counts_df = adsl)
resultMedDRA System Organ Class Placebo Xanomeline High Dose Xanomeline Low Dose All Patients
MedDRA Preferred Term (N=86) (N=72) (N=96) (N=306)
————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————
Total number of patients with at least one adverse event 69 (80.2%) 70 (97.2%) 86 (89.6%) 225 (73.5%)
Overall total number of events 301 436 454 1191
CARDIAC DISORDERS
Total number of patients with at least one adverse event 13 (15.1%) 15 (20.8%) 16 (16.7%) 44 (14.4%)
Total number of events 27 30 34 91
ATRIAL FIBRILLATION 1 (1.2%) 2 (2.8%) 2 (2.1%) 5 (1.6%)
ATRIAL FLUTTER 0 1 (1.4%) 1 (1.0%) 2 (0.7%)
ATRIAL HYPERTROPHY 1 (1.2%) 0 0 1 (0.3%)
ATRIOVENTRICULAR BLOCK FIRST DEGREE 1 (1.2%) 0 1 (1.0%) 2 (0.7%)
ATRIOVENTRICULAR BLOCK SECOND DEGREE 2 (2.3%) 1 (1.4%) 2 (2.1%) 5 (1.6%)
BRADYCARDIA 1 (1.2%) 0 0 1 (0.3%)
BUNDLE BRANCH BLOCK LEFT 1 (1.2%) 0 0 1 (0.3%)
BUNDLE BRANCH BLOCK RIGHT 1 (1.2%) 0 1 (1.0%) 2 (0.7%)
CARDIAC DISORDER 0 1 (1.4%) 0 1 (0.3%)
CARDIAC FAILURE CONGESTIVE 1 (1.2%) 0 0 1 (0.3%)
MYOCARDIAL INFARCTION 4 (4.7%) 4 (5.6%) 2 (2.1%) 10 (3.3%)
PALPITATIONS 0 0 2 (2.1%) 2 (0.7%)
SINUS ARRHYTHMIA 1 (1.2%) 0 0 1 (0.3%)
SINUS BRADYCARDIA 2 (2.3%) 8 (11.1%) 7 (7.3%) 17 (5.6%)
SUPRAVENTRICULAR EXTRASYSTOLES 1 (1.2%) 1 (1.4%) 1 (1.0%) 3 (1.0%)
SUPRAVENTRICULAR TACHYCARDIA 0 0 1 (1.0%) 1 (0.3%)
TACHYCARDIA 1 (1.2%) 0 0 1 (0.3%)
VENTRICULAR EXTRASYSTOLES 0 1 (1.4%) 2 (2.1%) 3 (1.0%)
VENTRICULAR HYPERTROPHY 1 (1.2%) 0 0 1 (0.3%)
WOLFF-PARKINSON-WHITE SYNDROME 0 0 1 (1.0%) 1 (0.3%)
CONGENITAL, FAMILIAL AND GENETIC DISORDERS
Total number of patients with at least one adverse event 0 2 (2.8%) 1 (1.0%) 3 (1.0%)
Total number of events 0 2 1 3
VENTRICULAR SEPTAL DEFECT 0 2 (2.8%) 1 (1.0%) 3 (1.0%)
EAR AND LABYRINTH DISORDERS
Total number of patients with at least one adverse event 1 (1.2%) 1 (1.4%) 2 (2.1%) 4 (1.3%)
Total number of events 2 1 3 6
CERUMEN IMPACTION 0 0 1 (1.0%) 1 (0.3%)
EAR PAIN 1 (1.2%) 0 0 1 (0.3%)
TINNITUS 0 0 1 (1.0%) 1 (0.3%)
VERTIGO 0 1 (1.4%) 1 (1.0%) 2 (0.7%)
EYE DISORDERS
Total number of patients with at least one adverse event 4 (4.7%) 1 (1.4%) 2 (2.1%) 7 (2.3%)
Total number of events 8 2 2 12
CONJUNCTIVAL HAEMORRHAGE 0 0 1 (1.0%) 1 (0.3%)
CONJUNCTIVITIS 2 (2.3%) 0 0 2 (0.7%)
EYE ALLERGY 1 (1.2%) 0 0 1 (0.3%)
EYE PRURITUS 1 (1.2%) 0 0 1 (0.3%)
EYE SWELLING 1 (1.2%) 0 0 1 (0.3%)
GLAUCOMA 1 (1.2%) 0 0 1 (0.3%)
VISION BLURRED 0 1 (1.4%) 1 (1.0%) 2 (0.7%)
GASTROINTESTINAL DISORDERS
Total number of patients with at least one adverse event 17 (19.8%) 20 (27.8%) 16 (16.7%) 53 (17.3%)
Total number of events 26 35 26 87
ABDOMINAL DISCOMFORT 0 1 (1.4%) 0 1 (0.3%)
ABDOMINAL PAIN 1 (1.2%) 1 (1.4%) 3 (3.1%) 5 (1.6%)
CONSTIPATION 1 (1.2%) 0 0 1 (0.3%)
DIARRHOEA 9 (10.5%) 3 (4.2%) 6 (6.2%) 18 (5.9%)
DYSPEPSIA 1 (1.2%) 1 (1.4%) 1 (1.0%) 3 (1.0%)
DYSPHAGIA 0 0 1 (1.0%) 1 (0.3%)
FLATULENCE 1 (1.2%) 0 0 1 (0.3%)
GASTROINTESTINAL HAEMORRHAGE 0 1 (1.4%) 0 1 (0.3%)
GASTROOESOPHAGEAL REFLUX DISEASE 1 (1.2%) 0 0 1 (0.3%)
GLOSSITIS 1 (1.2%) 0 0 1 (0.3%)
HIATUS HERNIA 1 (1.2%) 0 0 1 (0.3%)
NAUSEA 3 (3.5%) 6 (8.3%) 3 (3.1%) 12 (3.9%)
RECTAL HAEMORRHAGE 0 0 1 (1.0%) 1 (0.3%)
SALIVARY HYPERSECRETION 0 4 (5.6%) 0 4 (1.3%)
STOMACH DISCOMFORT 0 1 (1.4%) 0 1 (0.3%)
VOMITING 3 (3.5%) 6 (8.3%) 4 (4.2%) 13 (4.2%)
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
Total number of patients with at least one adverse event 21 (24.4%) 36 (50.0%) 51 (53.1%) 108 (35.3%)
Total number of events 48 118 126 292
APPLICATION SITE BLEEDING 0 0 1 (1.0%) 1 (0.3%)
APPLICATION SITE DERMATITIS 5 (5.8%) 7 (9.7%) 9 (9.4%) 21 (6.9%)
APPLICATION SITE DESQUAMATION 0 0 1 (1.0%) 1 (0.3%)
APPLICATION SITE DISCHARGE 0 1 (1.4%) 0 1 (0.3%)
APPLICATION SITE DISCOLOURATION 0 0 1 (1.0%) 1 (0.3%)
APPLICATION SITE ERYTHEMA 3 (3.5%) 14 (19.4%) 13 (13.5%) 30 (9.8%)
APPLICATION SITE INDURATION 1 (1.2%) 0 0 1 (0.3%)
APPLICATION SITE IRRITATION 3 (3.5%) 9 (12.5%) 9 (9.4%) 21 (6.9%)
APPLICATION SITE PAIN 0 2 (2.8%) 0 2 (0.7%)
APPLICATION SITE PERSPIRATION 0 2 (2.8%) 0 2 (0.7%)
APPLICATION SITE PRURITUS 6 (7.0%) 21 (29.2%) 23 (24.0%) 50 (16.3%)
APPLICATION SITE REACTION 1 (1.2%) 1 (1.4%) 0 2 (0.7%)
APPLICATION SITE SWELLING 0 2 (2.8%) 1 (1.0%) 3 (1.0%)
APPLICATION SITE URTICARIA 0 1 (1.4%) 2 (2.1%) 3 (1.0%)
APPLICATION SITE VESICLES 1 (1.2%) 5 (6.9%) 5 (5.2%) 11 (3.6%)
APPLICATION SITE WARMTH 0 0 1 (1.0%) 1 (0.3%)
ASTHENIA 1 (1.2%) 0 1 (1.0%) 2 (0.7%)
CHEST DISCOMFORT 0 1 (1.4%) 1 (1.0%) 2 (0.7%)
CHEST PAIN 0 2 (2.8%) 0 2 (0.7%)
CHILLS 1 (1.2%) 1 (1.4%) 1 (1.0%) 3 (1.0%)
CYST 0 0 1 (1.0%) 1 (0.3%)
FATIGUE 1 (1.2%) 5 (6.9%) 5 (5.2%) 11 (3.6%)
FEELING ABNORMAL 0 1 (1.4%) 0 1 (0.3%)
FEELING COLD 0 1 (1.4%) 0 1 (0.3%)
INFLAMMATION 0 0 1 (1.0%) 1 (0.3%)
MALAISE 0 2 (2.8%) 1 (1.0%) 3 (1.0%)
OEDEMA 0 0 2 (2.1%) 2 (0.7%)
OEDEMA PERIPHERAL 2 (2.3%) 2 (2.8%) 1 (1.0%) 5 (1.6%)
PAIN 0 1 (1.4%) 1 (1.0%) 2 (0.7%)
PYREXIA 2 (2.3%) 0 1 (1.0%) 3 (1.0%)
SECRETION DISCHARGE 0 0 1 (1.0%) 1 (0.3%)
SUDDEN DEATH 0 0 1 (1.0%) 1 (0.3%)
SWELLING 0 0 1 (1.0%) 1 (0.3%)
ULCER 0 0 1 (1.0%) 1 (0.3%)
HEPATOBILIARY DISORDERS
Total number of patients with at least one adverse event 1 (1.2%) 0 0 1 (0.3%)
Total number of events 1 0 0 1
HYPERBILIRUBINAEMIA 1 (1.2%) 0 0 1 (0.3%)
IMMUNE SYSTEM DISORDERS
Total number of patients with at least one adverse event 0 1 (1.4%) 1 (1.0%) 2 (0.7%)
Total number of events 0 1 2 3
HYPERSENSITIVITY 0 0 1 (1.0%) 1 (0.3%)
SEASONAL ALLERGY 0 1 (1.4%) 0 1 (0.3%)
INFECTIONS AND INFESTATIONS
Total number of patients with at least one adverse event 16 (18.6%) 13 (18.1%) 10 (10.4%) 39 (12.7%)
Total number of events 35 20 18 73
BRONCHITIS 1 (1.2%) 0 0 1 (0.3%)
CELLULITIS 0 0 1 (1.0%) 1 (0.3%)
CERVICITIS 1 (1.2%) 0 0 1 (0.3%)
CYSTITIS 1 (1.2%) 1 (1.4%) 0 2 (0.7%)
EAR INFECTION 2 (2.3%) 0 0 2 (0.7%)
GASTROENTERITIS VIRAL 1 (1.2%) 0 0 1 (0.3%)
HORDEOLUM 0 1 (1.4%) 0 1 (0.3%)
INFLUENZA 1 (1.2%) 1 (1.4%) 1 (1.0%) 3 (1.0%)
LOCALISED INFECTION 1 (1.2%) 0 1 (1.0%) 2 (0.7%)
LOWER RESPIRATORY TRACT INFECTION 0 1 (1.4%) 0 1 (0.3%)
NASOPHARYNGITIS 2 (2.3%) 6 (8.3%) 4 (4.2%) 12 (3.9%)
ONYCHOMYCOSIS 0 0 1 (1.0%) 1 (0.3%)
PNEUMONIA 0 0 1 (1.0%) 1 (0.3%)
RHINITIS 0 1 (1.4%) 0 1 (0.3%)
UPPER RESPIRATORY TRACT INFECTION 6 (7.0%) 3 (4.2%) 1 (1.0%) 10 (3.3%)
URINARY TRACT INFECTION 2 (2.3%) 1 (1.4%) 0 3 (1.0%)
VAGINAL MYCOSIS 1 (1.2%) 0 0 1 (0.3%)
VIRAL INFECTION 0 0 1 (1.0%) 1 (0.3%)
INJURY, POISONING AND PROCEDURAL COMPLICATIONS
Total number of patients with at least one adverse event 4 (4.7%) 5 (6.9%) 5 (5.2%) 14 (4.6%)
Total number of events 9 8 12 29
CONTUSION 1 (1.2%) 2 (2.8%) 1 (1.0%) 4 (1.3%)
EXCORIATION 2 (2.3%) 1 (1.4%) 1 (1.0%) 4 (1.3%)
FACIAL BONES FRACTURE 0 1 (1.4%) 0 1 (0.3%)
FALL 1 (1.2%) 1 (1.4%) 2 (2.1%) 4 (1.3%)
HIP FRACTURE 1 (1.2%) 2 (2.8%) 0 3 (1.0%)
JOINT DISLOCATION 0 0 1 (1.0%) 1 (0.3%)
SKIN LACERATION 1 (1.2%) 0 2 (2.1%) 3 (1.0%)
WOUND 0 0 1 (1.0%) 1 (0.3%)
INVESTIGATIONS
Total number of patients with at least one adverse event 10 (11.6%) 5 (6.9%) 8 (8.3%) 23 (7.5%)
Total number of events 19 6 15 40
BIOPSY 0 1 (1.4%) 0 1 (0.3%)
BIOPSY PROSTATE 0 1 (1.4%) 0 1 (0.3%)
BLOOD ALKALINE PHOSPHATASE INCREASED 1 (1.2%) 0 0 1 (0.3%)
BLOOD CHOLESTEROL INCREASED 0 1 (1.4%) 0 1 (0.3%)
BLOOD CREATINE PHOSPHOKINASE INCREASED 1 (1.2%) 0 0 1 (0.3%)
BLOOD GLUCOSE INCREASED 0 1 (1.4%) 1 (1.0%) 2 (0.7%)
BLOOD URINE PRESENT 1 (1.2%) 0 0 1 (0.3%)
BODY TEMPERATURE INCREASED 0 0 1 (1.0%) 1 (0.3%)
CYSTOSCOPY 1 (1.2%) 0 0 1 (0.3%)
ELECTROCARDIOGRAM ST SEGMENT DEPRESSION 4 (4.7%) 0 1 (1.0%) 5 (1.6%)
ELECTROCARDIOGRAM T WAVE AMPLITUDE DECREASED 1 (1.2%) 0 1 (1.0%) 2 (0.7%)
ELECTROCARDIOGRAM T WAVE INVERSION 2 (2.3%) 1 (1.4%) 1 (1.0%) 4 (1.3%)
HEART RATE INCREASED 1 (1.2%) 0 0 1 (0.3%)
HEART RATE IRREGULAR 1 (1.2%) 0 0 1 (0.3%)
NASAL MUCOSA BIOPSY 0 0 1 (1.0%) 1 (0.3%)
NEUTROPHIL COUNT INCREASED 0 0 1 (1.0%) 1 (0.3%)
URINE ANALYSIS ABNORMAL 0 0 1 (1.0%) 1 (0.3%)
WEIGHT DECREASED 0 0 1 (1.0%) 1 (0.3%)
WHITE BLOOD CELL COUNT INCREASED 0 0 1 (1.0%) 1 (0.3%)
METABOLISM AND NUTRITION DISORDERS
Total number of patients with at least one adverse event 6 (7.0%) 3 (4.2%) 1 (1.0%) 10 (3.3%)
Total number of events 8 5 1 14
DECREASED APPETITE 1 (1.2%) 1 (1.4%) 0 2 (0.7%)
DEHYDRATION 1 (1.2%) 0 0 1 (0.3%)
DIABETES MELLITUS 1 (1.2%) 0 0 1 (0.3%)
FOOD CRAVING 1 (1.2%) 0 1 (1.0%) 2 (0.7%)
HYPERCHOLESTEROLAEMIA 0 1 (1.4%) 0 1 (0.3%)
HYPONATRAEMIA 1 (1.2%) 0 0 1 (0.3%)
INCREASED APPETITE 1 (1.2%) 1 (1.4%) 0 2 (0.7%)
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Total number of patients with at least one adverse event 5 (5.8%) 8 (11.1%) 7 (7.3%) 20 (6.5%)
Total number of events 8 11 10 29
ARTHRALGIA 1 (1.2%) 1 (1.4%) 2 (2.1%) 4 (1.3%)
ARTHRITIS 1 (1.2%) 1 (1.4%) 0 2 (0.7%)
BACK PAIN 1 (1.2%) 3 (4.2%) 1 (1.0%) 5 (1.6%)
FLANK PAIN 0 2 (2.8%) 0 2 (0.7%)
MUSCLE SPASMS 0 1 (1.4%) 1 (1.0%) 2 (0.7%)
MUSCULAR WEAKNESS 0 0 1 (1.0%) 1 (0.3%)
MYALGIA 0 1 (1.4%) 0 1 (0.3%)
PAIN IN EXTREMITY 1 (1.2%) 0 0 1 (0.3%)
SHOULDER PAIN 1 (1.2%) 0 2 (2.1%) 3 (1.0%)
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)
Total number of patients with at least one adverse event 0 1 (1.4%) 2 (2.1%) 3 (1.0%)
Total number of events 0 1 3 4
COLON CANCER 0 0 1 (1.0%) 1 (0.3%)
MALIGNANT FIBROUS HISTIOCYTOMA 0 0 1 (1.0%) 1 (0.3%)
PROSTATE CANCER 0 1 (1.4%) 0 1 (0.3%)
NERVOUS SYSTEM DISORDERS
Total number of patients with at least one adverse event 12 (14.0%) 25 (34.7%) 22 (22.9%) 59 (19.3%)
Total number of events 16 43 42 101
AMNESIA 0 1 (1.4%) 0 1 (0.3%)
BALANCE DISORDER 0 0 1 (1.0%) 1 (0.3%)
BURNING SENSATION 0 2 (2.8%) 0 2 (0.7%)
COGNITIVE DISORDER 0 1 (1.4%) 0 1 (0.3%)
COMPLEX PARTIAL SEIZURES 0 0 1 (1.0%) 1 (0.3%)
COORDINATION ABNORMAL 0 0 1 (1.0%) 1 (0.3%)
DIZZINESS 2 (2.3%) 11 (15.3%) 9 (9.4%) 22 (7.2%)
HEADACHE 7 (8.1%) 6 (8.3%) 3 (3.1%) 16 (5.2%)
HEMIANOPIA HOMONYMOUS 0 0 1 (1.0%) 1 (0.3%)
HYPERSOMNIA 0 1 (1.4%) 0 1 (0.3%)
LETHARGY 0 1 (1.4%) 1 (1.0%) 2 (0.7%)
PARAESTHESIA 0 1 (1.4%) 0 1 (0.3%)
PARAESTHESIA ORAL 0 0 1 (1.0%) 1 (0.3%)
PARKINSON'S DISEASE 1 (1.2%) 0 0 1 (0.3%)
PAROSMIA 0 1 (1.4%) 0 1 (0.3%)
PARTIAL SEIZURES WITH SECONDARY GENERALISATION 0 1 (1.4%) 0 1 (0.3%)
PSYCHOMOTOR HYPERACTIVITY 1 (1.2%) 0 0 1 (0.3%)
SOMNOLENCE 2 (2.3%) 1 (1.4%) 3 (3.1%) 6 (2.0%)
STUPOR 0 0 1 (1.0%) 1 (0.3%)
SYNCOPE 0 2 (2.8%) 5 (5.2%) 7 (2.3%)
SYNCOPE VASOVAGAL 0 1 (1.4%) 0 1 (0.3%)
TRANSIENT ISCHAEMIC ATTACK 0 1 (1.4%) 2 (2.1%) 3 (1.0%)
PSYCHIATRIC DISORDERS
Total number of patients with at least one adverse event 10 (11.6%) 8 (11.1%) 11 (11.5%) 29 (9.5%)
Total number of events 14 11 15 40
AGITATION 2 (2.3%) 0 3 (3.1%) 5 (1.6%)
ANXIETY 1 (1.2%) 0 3 (3.1%) 4 (1.3%)
COMPLETED SUICIDE 1 (1.2%) 0 0 1 (0.3%)
CONFUSIONAL STATE 2 (2.3%) 1 (1.4%) 3 (3.1%) 6 (2.0%)
DELIRIUM 0 1 (1.4%) 0 1 (0.3%)
DELUSION 1 (1.2%) 1 (1.4%) 0 2 (0.7%)
DEPRESSED MOOD 0 1 (1.4%) 1 (1.0%) 2 (0.7%)
DISORIENTATION 1 (1.2%) 0 0 1 (0.3%)
HALLUCINATION 0 1 (1.4%) 0 1 (0.3%)
HALLUCINATION, VISUAL 0 1 (1.4%) 0 1 (0.3%)
INSOMNIA 2 (2.3%) 2 (2.8%) 0 4 (1.3%)
IRRITABILITY 1 (1.2%) 0 1 (1.0%) 2 (0.7%)
LIBIDO DECREASED 0 1 (1.4%) 0 1 (0.3%)
LISTLESS 0 1 (1.4%) 0 1 (0.3%)
NIGHTMARE 0 1 (1.4%) 0 1 (0.3%)
RESTLESSNESS 0 0 1 (1.0%) 1 (0.3%)
RENAL AND URINARY DISORDERS
Total number of patients with at least one adverse event 4 (4.7%) 3 (4.2%) 4 (4.2%) 11 (3.6%)
Total number of events 5 4 4 13
CALCULUS URETHRAL 0 1 (1.4%) 0 1 (0.3%)
DYSURIA 1 (1.2%) 0 1 (1.0%) 2 (0.7%)
ENURESIS 0 0 1 (1.0%) 1 (0.3%)
INCONTINENCE 0 0 1 (1.0%) 1 (0.3%)
MICTURITION URGENCY 1 (1.2%) 1 (1.4%) 1 (1.0%) 3 (1.0%)
NEPHROLITHIASIS 1 (1.2%) 1 (1.4%) 0 2 (0.7%)
POLLAKIURIA 1 (1.2%) 0 0 1 (0.3%)
REPRODUCTIVE SYSTEM AND BREAST DISORDERS
Total number of patients with at least one adverse event 2 (2.3%) 1 (1.4%) 0 3 (1.0%)
Total number of events 4 1 0 5
BENIGN PROSTATIC HYPERPLASIA 1 (1.2%) 1 (1.4%) 0 2 (0.7%)
PELVIC PAIN 1 (1.2%) 0 0 1 (0.3%)
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
Total number of patients with at least one adverse event 10 (11.6%) 10 (13.9%) 10 (10.4%) 30 (9.8%)
Total number of events 15 22 16 53
ALLERGIC GRANULOMATOUS ANGIITIS 0 1 (1.4%) 0 1 (0.3%)
COUGH 3 (3.5%) 5 (6.9%) 6 (6.2%) 14 (4.6%)
DYSPHONIA 0 0 1 (1.0%) 1 (0.3%)
DYSPNOEA 1 (1.2%) 1 (1.4%) 1 (1.0%) 3 (1.0%)
EMPHYSEMA 1 (1.2%) 0 0 1 (0.3%)
EPISTAXIS 0 2 (2.8%) 1 (1.0%) 3 (1.0%)
HAEMOPTYSIS 1 (1.2%) 0 0 1 (0.3%)
NASAL CONGESTION 3 (3.5%) 3 (4.2%) 1 (1.0%) 7 (2.3%)
PHARYNGEAL ERYTHEMA 0 1 (1.4%) 0 1 (0.3%)
PHARYNGOLARYNGEAL PAIN 0 1 (1.4%) 1 (1.0%) 2 (0.7%)
POSTNASAL DRIP 1 (1.2%) 0 0 1 (0.3%)
PRODUCTIVE COUGH 0 1 (1.4%) 0 1 (0.3%)
RALES 1 (1.2%) 0 0 1 (0.3%)
RESPIRATORY TRACT CONGESTION 0 1 (1.4%) 0 1 (0.3%)
RHINORRHOEA 0 1 (1.4%) 1 (1.0%) 2 (0.7%)
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Total number of patients with at least one adverse event 21 (24.4%) 42 (58.3%) 42 (43.8%) 105 (34.3%)
Total number of events 47 111 118 276
ACTINIC KERATOSIS 0 1 (1.4%) 0 1 (0.3%)
ALOPECIA 1 (1.2%) 0 0 1 (0.3%)
BLISTER 0 1 (1.4%) 5 (5.2%) 6 (2.0%)
COLD SWEAT 1 (1.2%) 0 0 1 (0.3%)
DERMATITIS ATOPIC 1 (1.2%) 0 0 1 (0.3%)
DERMATITIS CONTACT 0 0 1 (1.0%) 1 (0.3%)
DRUG ERUPTION 1 (1.2%) 0 0 1 (0.3%)
ERYTHEMA 9 (10.5%) 14 (19.4%) 15 (15.6%) 38 (12.4%)
HYPERHIDROSIS 2 (2.3%) 8 (11.1%) 4 (4.2%) 14 (4.6%)
PRURITUS 8 (9.3%) 26 (36.1%) 23 (24.0%) 57 (18.6%)
PRURITUS GENERALISED 0 1 (1.4%) 1 (1.0%) 2 (0.7%)
RASH 5 (5.8%) 11 (15.3%) 13 (13.5%) 29 (9.5%)
RASH ERYTHEMATOUS 0 0 2 (2.1%) 2 (0.7%)
RASH MACULO-PAPULAR 0 1 (1.4%) 0 1 (0.3%)
RASH PAPULAR 0 1 (1.4%) 0 1 (0.3%)
RASH PRURITIC 0 2 (2.8%) 1 (1.0%) 3 (1.0%)
SKIN EXFOLIATION 0 0 1 (1.0%) 1 (0.3%)
SKIN IRRITATION 3 (3.5%) 5 (6.9%) 6 (6.2%) 14 (4.6%)
SKIN ODOUR ABNORMAL 0 1 (1.4%) 0 1 (0.3%)
SKIN ULCER 1 (1.2%) 0 0 1 (0.3%)
URTICARIA 0 1 (1.4%) 1 (1.0%) 2 (0.7%)
SOCIAL CIRCUMSTANCES
Total number of patients with at least one adverse event 0 1 (1.4%) 0 1 (0.3%)
Total number of events 0 1 0 1
ALCOHOL USE 0 1 (1.4%) 0 1 (0.3%)
SURGICAL AND MEDICAL PROCEDURES
Total number of patients with at least one adverse event 2 (2.3%) 2 (2.8%) 1 (1.0%) 5 (1.6%)
Total number of events 2 2 1 5
ACROCHORDON EXCISION 0 1 (1.4%) 0 1 (0.3%)
CATARACT OPERATION 1 (1.2%) 0 1 (1.0%) 2 (0.7%)
EYE LASER SURGERY 1 (1.2%) 0 0 1 (0.3%)
SKIN LESION EXCISION 0 1 (1.4%) 0 1 (0.3%)
VASCULAR DISORDERS
Total number of patients with at least one adverse event 3 (3.5%) 1 (1.4%) 4 (4.2%) 8 (2.6%)
Total number of events 7 1 5 13
HOT FLUSH 0 0 1 (1.0%) 1 (0.3%)
HYPERTENSION 1 (1.2%) 0 2 (2.1%) 3 (1.0%)
HYPOTENSION 2 (2.3%) 0 1 (1.0%) 3 (1.0%)
ORTHOSTATIC HYPOTENSION 1 (1.2%) 0 0 1 (0.3%)
WOUND HAEMORRHAGE 0 1 (1.4%) 0 1 (0.3%) {tfrmt} & {cards}
In the example below, we will use the {tfrmt} and {cards} packages to create a adverse events tables.
- The {cards} package creates Analysis Results Datasets (ARDs, which are a part of the CDISC Analysis Results Standard).
- The {tfrmt} utilizes ARDs to create tables.
In the example below, we first build an ARD with the needed summary statistics using {cards}. Then, we use the ARD to build the adverse events table with {tfrmt}.
Load libraries
Step 1: Import data
Subset to safety population.
Step 2: Data Preparation
Analysis
Create an Analysis Result Display (ARD) using the {cards} package.
# Create an ARD that stacks hierarchical data of adverse events
# Grouping by treatment, system organ class, and preferred term
ae_ard <- ard_stack_hierarchical(
data = adae,
by = TRT01A, # Note: by variables must be present in the denominator dataset
variables = c(AEBODSYS, AETERM),
statistic = ~ c("n", "p"), # Calculate count and percentage
denominator = adsl,
id = USUBJID,
over_variables = TRUE,
overall = TRUE
)
# Filter adae and adsl with trt01a set to "Total" and create a new ARD for the total column
adae2 <- adae |>
mutate(TRT01A = "Total")
adsl2 <- adsl |>
mutate(TRT01A = "Total")
ae2_ard <- ard_stack_hierarchical(
data = adae2,
by = TRT01A, # Note: by variables must be present in the denominator dataset
variables = c(AEBODSYS, AETERM),
denominator = adsl2,
statistic = ~ c("n", "p"),
id = USUBJID,
over_variables = TRUE,
overall = TRUE
) |>
filter(group2 == "TRT01A" | variable == "TRT01A") # filter to stats we needTidy for table
Further refine the ARD for use in tfrmt
ae3_ard <- bind_ard(ae_ard, ae2_ard) |>
# reshape the data
shuffle_card(fill_hierarchical_overall = "ANY EVENT") |>
# transform group-level freqs/pcts into a singular "bigN" row
prep_big_n(vars = "TRT01A") |>
# for nested variables, fill any missing values with "ANY EVENT"
prep_hierarchical_fill(vars = c("AEBODSYS", "AETERM"), fill = "ANY EVENT") |>
mutate(TRT01A = ifelse(TRT01A == "Overall TRT01A", "Total", TRT01A))
# create ordering columns, sort by AEBODSYS
ordering_aebodsys <- ae3_ard |>
filter(TRT01A == "Total", stat_name == "n", AETERM == "ANY EVENT") |>
arrange(desc(stat)) |>
mutate(ord1 = row_number()) |>
select(AEBODSYS, ord1)
# sort by AETERM after AEBODSYS order
ordering_aeterm <- ae3_ard |>
filter(TRT01A == "Total", stat_name == "n") |>
group_by(AEBODSYS) |>
arrange(desc(stat)) |>
mutate(ord2 = row_number()) |>
select(AEBODSYS, AETERM, ord2)
# join on our ordering columns and keep required columns
ae4_ard <- ae3_ard |>
full_join(ordering_aebodsys, by = "AEBODSYS") |>
full_join(ordering_aeterm, by = c("AEBODSYS", "AETERM")) |>
select(AEBODSYS, AETERM, ord1, ord2, stat, stat_name, TRT01A)Step 3: Creating the {tfrmt} Table
AE_T01 <- tfrmt_n_pct(
n = "n", pct = "p",
pct_frmt_when = frmt_when(
"==1" ~ frmt("(100%)"),
">=0.995" ~ frmt("(>99%)"),
"==0" ~ frmt(""),
"<=0.01" ~ frmt("(<1%)"),
"TRUE" ~ frmt("(xx.x%)", transform = ~ . * 100)
)
) |>
tfrmt(
group = AEBODSYS,
label = AETERM,
param = stat_name,
value = stat,
column = TRT01A,
sorting_cols = c(ord1, ord2),
col_plan = col_plan(
"System Organ Class
Preferred Term" = AEBODSYS, Placebo, `Xanomeline High Dose`, `Xanomeline Low Dose`,
-ord1, -ord2
),
row_grp_plan = row_grp_plan(row_grp_structure(
group_val = ".default", element_block(post_space = " ")
)),
big_n = big_n_structure(param_val = "bigN", n_frmt = frmt(" (N=xx)"))
) |>
print_to_gt(ae4_ard)
AE_T01| System Organ Class Preferred Term | Placebo (N=86) | Xanomeline High Dose (N=72) | Xanomeline Low Dose (N=96) | Total (N=254) |
|---|---|---|---|---|
| ANY EVENT | 65 (75.6%) | 68 (94.4%) | 84 (87.5%) | 217 (85.4%) |
| GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | ||||
| ANY EVENT | 21 (24.4%) | 36 (50.0%) | 51 (53.1%) | 108 (42.5%) |
| APPLICATION SITE PRURITUS | 6 ( 7.0%) | 21 (29.2%) | 23 (24.0%) | 50 (19.7%) |
| APPLICATION SITE ERYTHEMA | 3 ( 3.5%) | 14 (19.4%) | 13 (13.5%) | 30 (11.8%) |
| APPLICATION SITE DERMATITIS | 5 ( 5.8%) | 7 ( 9.7%) | 9 ( 9.4%) | 21 ( 8.3%) |
| APPLICATION SITE IRRITATION | 3 ( 3.5%) | 9 (12.5%) | 9 ( 9.4%) | 21 ( 8.3%) |
| APPLICATION SITE VESICLES | 1 ( 1.2%) | 5 ( 6.9%) | 5 ( 5.2%) | 11 ( 4.3%) |
| FATIGUE | 1 ( 1.2%) | 5 ( 6.9%) | 5 ( 5.2%) | 11 ( 4.3%) |
| OEDEMA PERIPHERAL | 2 ( 2.3%) | 2 ( 2.8%) | 1 ( 1.0%) | 5 ( 2.0%) |
| APPLICATION SITE SWELLING | 0 | 2 ( 2.8%) | 1 ( 1.0%) | 3 ( 1.2%) |
| APPLICATION SITE URTICARIA | 0 | 1 ( 1.4%) | 2 ( 2.1%) | 3 ( 1.2%) |
| CHILLS | 1 ( 1.2%) | 1 ( 1.4%) | 1 ( 1.0%) | 3 ( 1.2%) |
| MALAISE | 0 | 2 ( 2.8%) | 1 ( 1.0%) | 3 ( 1.2%) |
| PYREXIA | 2 ( 2.3%) | 0 | 1 ( 1.0%) | 3 ( 1.2%) |
| APPLICATION SITE PAIN | 0 | 2 ( 2.8%) | 0 | 2 (<1%) |
| APPLICATION SITE PERSPIRATION | 0 | 2 ( 2.8%) | 0 | 2 (<1%) |
| APPLICATION SITE REACTION | 1 ( 1.2%) | 1 ( 1.4%) | 0 | 2 (<1%) |
| ASTHENIA | 1 ( 1.2%) | 0 | 1 ( 1.0%) | 2 (<1%) |
| CHEST DISCOMFORT | 0 | 1 ( 1.4%) | 1 ( 1.0%) | 2 (<1%) |
| CHEST PAIN | 0 | 2 ( 2.8%) | 0 | 2 (<1%) |
| OEDEMA | 0 | 0 | 2 ( 2.1%) | 2 (<1%) |
| PAIN | 0 | 1 ( 1.4%) | 1 ( 1.0%) | 2 (<1%) |
| APPLICATION SITE BLEEDING | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| APPLICATION SITE DESQUAMATION | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| APPLICATION SITE DISCHARGE | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| APPLICATION SITE DISCOLOURATION | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| APPLICATION SITE INDURATION | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| APPLICATION SITE WARMTH | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| FEELING ABNORMAL | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| FEELING COLD | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| INFLAMMATION | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| SECRETION DISCHARGE | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| SUDDEN DEATH | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| SWELLING | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| ULCER | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS | ||||
| ANY EVENT | 20 (23.3%) | 39 (54.2%) | 39 (40.6%) | 98 (38.6%) |
| PRURITUS | 8 ( 9.3%) | 25 (34.7%) | 21 (21.9%) | 54 (21.3%) |
| ERYTHEMA | 8 ( 9.3%) | 14 (19.4%) | 14 (14.6%) | 36 (14.2%) |
| RASH | 5 ( 5.8%) | 8 (11.1%) | 13 (13.5%) | 26 (10.2%) |
| HYPERHIDROSIS | 2 ( 2.3%) | 8 (11.1%) | 4 ( 4.2%) | 14 ( 5.5%) |
| SKIN IRRITATION | 3 ( 3.5%) | 5 ( 6.9%) | 6 ( 6.2%) | 14 ( 5.5%) |
| BLISTER | 0 | 1 ( 1.4%) | 5 ( 5.2%) | 6 ( 2.4%) |
| RASH PRURITIC | 0 | 2 ( 2.8%) | 1 ( 1.0%) | 3 ( 1.2%) |
| PRURITUS GENERALISED | 0 | 1 ( 1.4%) | 1 ( 1.0%) | 2 (<1%) |
| URTICARIA | 0 | 1 ( 1.4%) | 1 ( 1.0%) | 2 (<1%) |
| ACTINIC KERATOSIS | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| ALOPECIA | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| COLD SWEAT | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| DERMATITIS CONTACT | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| DRUG ERUPTION | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| RASH ERYTHEMATOUS | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| RASH MACULO-PAPULAR | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| SKIN EXFOLIATION | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| SKIN ODOUR ABNORMAL | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| SKIN ULCER | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| NERVOUS SYSTEM DISORDERS | ||||
| ANY EVENT | 8 ( 9.3%) | 23 (31.9%) | 22 (22.9%) | 53 (20.9%) |
| DIZZINESS | 2 ( 2.3%) | 10 (13.9%) | 9 ( 9.4%) | 21 ( 8.3%) |
| HEADACHE | 3 ( 3.5%) | 5 ( 6.9%) | 3 ( 3.1%) | 11 ( 4.3%) |
| SYNCOPE | 0 | 2 ( 2.8%) | 5 ( 5.2%) | 7 ( 2.8%) |
| SOMNOLENCE | 2 ( 2.3%) | 1 ( 1.4%) | 3 ( 3.1%) | 6 ( 2.4%) |
| TRANSIENT ISCHAEMIC ATTACK | 0 | 1 ( 1.4%) | 2 ( 2.1%) | 3 ( 1.2%) |
| BURNING SENSATION | 0 | 2 ( 2.8%) | 0 | 2 (<1%) |
| LETHARGY | 0 | 1 ( 1.4%) | 1 ( 1.0%) | 2 (<1%) |
| AMNESIA | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| BALANCE DISORDER | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| COGNITIVE DISORDER | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| COMPLEX PARTIAL SEIZURES | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| COORDINATION ABNORMAL | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| HEMIANOPIA HOMONYMOUS | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| HYPERSOMNIA | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| PARAESTHESIA | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| PARAESTHESIA ORAL | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| PARKINSON'S DISEASE | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| PAROSMIA | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| PARTIAL SEIZURES WITH SECONDARY GENERALISATION | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| PSYCHOMOTOR HYPERACTIVITY | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| STUPOR | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| SYNCOPE VASOVAGAL | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| GASTROINTESTINAL DISORDERS | ||||
| ANY EVENT | 17 (19.8%) | 19 (26.4%) | 15 (15.6%) | 51 (20.1%) |
| DIARRHOEA | 9 (10.5%) | 3 ( 4.2%) | 5 ( 5.2%) | 17 ( 6.7%) |
| VOMITING | 3 ( 3.5%) | 6 ( 8.3%) | 4 ( 4.2%) | 13 ( 5.1%) |
| NAUSEA | 3 ( 3.5%) | 6 ( 8.3%) | 3 ( 3.1%) | 12 ( 4.7%) |
| ABDOMINAL PAIN | 1 ( 1.2%) | 1 ( 1.4%) | 3 ( 3.1%) | 5 ( 2.0%) |
| SALIVARY HYPERSECRETION | 0 | 4 ( 5.6%) | 0 | 4 ( 1.6%) |
| DYSPEPSIA | 1 ( 1.2%) | 0 | 1 ( 1.0%) | 2 (<1%) |
| ABDOMINAL DISCOMFORT | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| CONSTIPATION | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| DYSPHAGIA | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| FLATULENCE | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| GASTROINTESTINAL HAEMORRHAGE | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| GASTROOESOPHAGEAL REFLUX DISEASE | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| GLOSSITIS | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| HIATUS HERNIA | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| RECTAL HAEMORRHAGE | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| STOMACH DISCOMFORT | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| CARDIAC DISORDERS | ||||
| ANY EVENT | 12 (14.0%) | 14 (19.4%) | 14 (14.6%) | 40 (15.7%) |
| SINUS BRADYCARDIA | 2 ( 2.3%) | 8 (11.1%) | 7 ( 7.3%) | 17 ( 6.7%) |
| MYOCARDIAL INFARCTION | 4 ( 4.7%) | 4 ( 5.6%) | 2 ( 2.1%) | 10 ( 3.9%) |
| ATRIAL FIBRILLATION | 1 ( 1.2%) | 2 ( 2.8%) | 2 ( 2.1%) | 5 ( 2.0%) |
| SUPRAVENTRICULAR EXTRASYSTOLES | 1 ( 1.2%) | 1 ( 1.4%) | 1 ( 1.0%) | 3 ( 1.2%) |
| VENTRICULAR EXTRASYSTOLES | 0 | 1 ( 1.4%) | 2 ( 2.1%) | 3 ( 1.2%) |
| ATRIAL FLUTTER | 0 | 1 ( 1.4%) | 1 ( 1.0%) | 2 (<1%) |
| ATRIOVENTRICULAR BLOCK FIRST DEGREE | 1 ( 1.2%) | 0 | 1 ( 1.0%) | 2 (<1%) |
| BUNDLE BRANCH BLOCK RIGHT | 1 ( 1.2%) | 0 | 1 ( 1.0%) | 2 (<1%) |
| PALPITATIONS | 0 | 0 | 2 ( 2.1%) | 2 (<1%) |
| ATRIAL HYPERTROPHY | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| ATRIOVENTRICULAR BLOCK SECOND DEGREE | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| BRADYCARDIA | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| BUNDLE BRANCH BLOCK LEFT | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| CARDIAC DISORDER | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| CARDIAC FAILURE CONGESTIVE | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| SINUS ARRHYTHMIA | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| SUPRAVENTRICULAR TACHYCARDIA | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| TACHYCARDIA | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| VENTRICULAR HYPERTROPHY | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| WOLFF-PARKINSON-WHITE SYNDROME | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| INFECTIONS AND INFESTATIONS | ||||
| ANY EVENT | 16 (18.6%) | 13 (18.1%) | 9 ( 9.4%) | 38 (15.0%) |
| NASOPHARYNGITIS | 2 ( 2.3%) | 6 ( 8.3%) | 4 ( 4.2%) | 12 ( 4.7%) |
| UPPER RESPIRATORY TRACT INFECTION | 6 ( 7.0%) | 3 ( 4.2%) | 1 ( 1.0%) | 10 ( 3.9%) |
| INFLUENZA | 1 ( 1.2%) | 1 ( 1.4%) | 1 ( 1.0%) | 3 ( 1.2%) |
| URINARY TRACT INFECTION | 2 ( 2.3%) | 1 ( 1.4%) | 0 | 3 ( 1.2%) |
| CYSTITIS | 1 ( 1.2%) | 1 ( 1.4%) | 0 | 2 (<1%) |
| EAR INFECTION | 2 ( 2.3%) | 0 | 0 | 2 (<1%) |
| BRONCHITIS | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| CELLULITIS | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| CERVICITIS | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| GASTROENTERITIS VIRAL | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| HORDEOLUM | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| LOCALISED INFECTION | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| LOWER RESPIRATORY TRACT INFECTION | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| PNEUMONIA | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| RHINITIS | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| VAGINAL MYCOSIS | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| VIRAL INFECTION | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| PSYCHIATRIC DISORDERS | ||||
| ANY EVENT | 10 (11.6%) | 7 ( 9.7%) | 11 (11.5%) | 28 (11.0%) |
| CONFUSIONAL STATE | 2 ( 2.3%) | 1 ( 1.4%) | 3 ( 3.1%) | 6 ( 2.4%) |
| AGITATION | 2 ( 2.3%) | 0 | 3 ( 3.1%) | 5 ( 2.0%) |
| INSOMNIA | 2 ( 2.3%) | 2 ( 2.8%) | 0 | 4 ( 1.6%) |
| ANXIETY | 0 | 0 | 3 ( 3.1%) | 3 ( 1.2%) |
| DELUSION | 1 ( 1.2%) | 1 ( 1.4%) | 0 | 2 (<1%) |
| IRRITABILITY | 1 ( 1.2%) | 0 | 1 ( 1.0%) | 2 (<1%) |
| COMPLETED SUICIDE | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| DELIRIUM | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| DEPRESSED MOOD | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| DISORIENTATION | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| HALLUCINATION | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| HALLUCINATION, VISUAL | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| LIBIDO DECREASED | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| LISTLESS | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| NIGHTMARE | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| RESTLESSNESS | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS | ||||
| ANY EVENT | 8 ( 9.3%) | 10 (13.9%) | 9 ( 9.4%) | 27 (10.6%) |
| COUGH | 1 ( 1.2%) | 5 ( 6.9%) | 5 ( 5.2%) | 11 ( 4.3%) |
| NASAL CONGESTION | 3 ( 3.5%) | 3 ( 4.2%) | 1 ( 1.0%) | 7 ( 2.8%) |
| DYSPNOEA | 1 ( 1.2%) | 1 ( 1.4%) | 1 ( 1.0%) | 3 ( 1.2%) |
| EPISTAXIS | 0 | 2 ( 2.8%) | 1 ( 1.0%) | 3 ( 1.2%) |
| PHARYNGOLARYNGEAL PAIN | 0 | 1 ( 1.4%) | 1 ( 1.0%) | 2 (<1%) |
| RHINORRHOEA | 0 | 1 ( 1.4%) | 1 ( 1.0%) | 2 (<1%) |
| ALLERGIC GRANULOMATOUS ANGIITIS | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| DYSPHONIA | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| EMPHYSEMA | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| HAEMOPTYSIS | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| PHARYNGEAL ERYTHEMA | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| POSTNASAL DRIP | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| PRODUCTIVE COUGH | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| RALES | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| RESPIRATORY TRACT CONGESTION | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| INVESTIGATIONS | ||||
| ANY EVENT | 10 (11.6%) | 5 ( 6.9%) | 7 ( 7.3%) | 22 ( 8.7%) |
| ELECTROCARDIOGRAM ST SEGMENT DEPRESSION | 4 ( 4.7%) | 0 | 1 ( 1.0%) | 5 ( 2.0%) |
| ELECTROCARDIOGRAM T WAVE INVERSION | 2 ( 2.3%) | 1 ( 1.4%) | 1 ( 1.0%) | 4 ( 1.6%) |
| BLOOD GLUCOSE INCREASED | 0 | 1 ( 1.4%) | 1 ( 1.0%) | 2 (<1%) |
| ELECTROCARDIOGRAM T WAVE AMPLITUDE DECREASED | 1 ( 1.2%) | 0 | 1 ( 1.0%) | 2 (<1%) |
| BIOPSY | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| BIOPSY PROSTATE | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| BLOOD ALKALINE PHOSPHATASE INCREASED | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| BLOOD CHOLESTEROL INCREASED | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| BLOOD CREATINE PHOSPHOKINASE INCREASED | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| BLOOD URINE PRESENT | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| BODY TEMPERATURE INCREASED | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| CYSTOSCOPY | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| HEART RATE INCREASED | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| HEART RATE IRREGULAR | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| NASAL MUCOSA BIOPSY | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| WEIGHT DECREASED | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS | ||||
| ANY EVENT | 4 ( 4.7%) | 7 ( 9.7%) | 7 ( 7.3%) | 18 ( 7.1%) |
| BACK PAIN | 1 ( 1.2%) | 3 ( 4.2%) | 1 ( 1.0%) | 5 ( 2.0%) |
| ARTHRALGIA | 1 ( 1.2%) | 1 ( 1.4%) | 2 ( 2.1%) | 4 ( 1.6%) |
| SHOULDER PAIN | 1 ( 1.2%) | 0 | 2 ( 2.1%) | 3 ( 1.2%) |
| MUSCLE SPASMS | 0 | 1 ( 1.4%) | 1 ( 1.0%) | 2 (<1%) |
| ARTHRITIS | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| FLANK PAIN | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| MUSCULAR WEAKNESS | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| MYALGIA | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| PAIN IN EXTREMITY | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| INJURY, POISONING AND PROCEDURAL COMPLICATIONS | ||||
| ANY EVENT | 4 ( 4.7%) | 5 ( 6.9%) | 5 ( 5.2%) | 14 ( 5.5%) |
| CONTUSION | 1 ( 1.2%) | 2 ( 2.8%) | 1 ( 1.0%) | 4 ( 1.6%) |
| EXCORIATION | 2 ( 2.3%) | 1 ( 1.4%) | 1 ( 1.0%) | 4 ( 1.6%) |
| FALL | 1 ( 1.2%) | 1 ( 1.4%) | 2 ( 2.1%) | 4 ( 1.6%) |
| HIP FRACTURE | 1 ( 1.2%) | 2 ( 2.8%) | 0 | 3 ( 1.2%) |
| SKIN LACERATION | 1 ( 1.2%) | 0 | 2 ( 2.1%) | 3 ( 1.2%) |
| FACIAL BONES FRACTURE | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| JOINT DISLOCATION | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| WOUND | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| RENAL AND URINARY DISORDERS | ||||
| ANY EVENT | 4 ( 4.7%) | 3 ( 4.2%) | 3 ( 3.1%) | 10 ( 3.9%) |
| MICTURITION URGENCY | 1 ( 1.2%) | 1 ( 1.4%) | 1 ( 1.0%) | 3 ( 1.2%) |
| DYSURIA | 1 ( 1.2%) | 0 | 1 ( 1.0%) | 2 (<1%) |
| NEPHROLITHIASIS | 1 ( 1.2%) | 1 ( 1.4%) | 0 | 2 (<1%) |
| CALCULUS URETHRAL | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| INCONTINENCE | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| POLLAKIURIA | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| METABOLISM AND NUTRITION DISORDERS | ||||
| ANY EVENT | 6 ( 7.0%) | 2 ( 2.8%) | 1 ( 1.0%) | 9 ( 3.5%) |
| DECREASED APPETITE | 1 ( 1.2%) | 1 ( 1.4%) | 0 | 2 (<1%) |
| FOOD CRAVING | 1 ( 1.2%) | 0 | 1 ( 1.0%) | 2 (<1%) |
| INCREASED APPETITE | 1 ( 1.2%) | 1 ( 1.4%) | 0 | 2 (<1%) |
| DEHYDRATION | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| DIABETES MELLITUS | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| HYPONATRAEMIA | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| VASCULAR DISORDERS | ||||
| ANY EVENT | 3 ( 3.5%) | 1 ( 1.4%) | 3 ( 3.1%) | 7 ( 2.8%) |
| HYPOTENSION | 2 ( 2.3%) | 0 | 1 ( 1.0%) | 3 ( 1.2%) |
| HYPERTENSION | 1 ( 1.2%) | 0 | 1 ( 1.0%) | 2 (<1%) |
| HOT FLUSH | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| ORTHOSTATIC HYPOTENSION | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| WOUND HAEMORRHAGE | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| EYE DISORDERS | ||||
| ANY EVENT | 2 ( 2.3%) | 1 ( 1.4%) | 2 ( 2.1%) | 5 ( 2.0%) |
| VISION BLURRED | 0 | 1 ( 1.4%) | 1 ( 1.0%) | 2 (<1%) |
| CONJUNCTIVAL HAEMORRHAGE | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| CONJUNCTIVITIS | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| EYE ALLERGY | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| EYE PRURITUS | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| EYE SWELLING | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| SURGICAL AND MEDICAL PROCEDURES | ||||
| ANY EVENT | 2 ( 2.3%) | 2 ( 2.8%) | 1 ( 1.0%) | 5 ( 2.0%) |
| CATARACT OPERATION | 1 ( 1.2%) | 0 | 1 ( 1.0%) | 2 (<1%) |
| ACROCHORDON EXCISION | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| EYE LASER SURGERY | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| SKIN LESION EXCISION | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| EAR AND LABYRINTH DISORDERS | ||||
| ANY EVENT | 1 ( 1.2%) | 1 ( 1.4%) | 2 ( 2.1%) | 4 ( 1.6%) |
| VERTIGO | 0 | 1 ( 1.4%) | 1 ( 1.0%) | 2 (<1%) |
| CERUMEN IMPACTION | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| EAR PAIN | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| CONGENITAL, FAMILIAL AND GENETIC DISORDERS | ||||
| ANY EVENT | 0 | 2 ( 2.8%) | 1 ( 1.0%) | 3 ( 1.2%) |
| VENTRICULAR SEPTAL DEFECT | 0 | 2 ( 2.8%) | 1 ( 1.0%) | 3 ( 1.2%) |
| NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) | ||||
| ANY EVENT | 0 | 1 ( 1.4%) | 2 ( 2.1%) | 3 ( 1.2%) |
| COLON CANCER | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| MALIGNANT FIBROUS HISTIOCYTOMA | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| PROSTATE CANCER | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| REPRODUCTIVE SYSTEM AND BREAST DISORDERS | ||||
| ANY EVENT | 2 ( 2.3%) | 1 ( 1.4%) | 0 | 3 ( 1.2%) |
| BENIGN PROSTATIC HYPERPLASIA | 1 ( 1.2%) | 1 ( 1.4%) | 0 | 2 (<1%) |
| PELVIC PAIN | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| HEPATOBILIARY DISORDERS | ||||
| ANY EVENT | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| HYPERBILIRUBINAEMIA | 1 ( 1.2%) | 0 | 0 | 1 (<1%) |
| IMMUNE SYSTEM DISORDERS | ||||
| ANY EVENT | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| HYPERSENSITIVITY | 0 | 0 | 1 ( 1.0%) | 1 (<1%) |
| SOCIAL CIRCUMSTANCES | ||||
| ANY EVENT | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |
| ALCOHOL USE | 0 | 1 ( 1.4%) | 0 | 1 (<1%) |