# Outcome codebook: which serious adverse-event terms count toward each outcome

Trials on ClinicalTrials.gov report serious adverse events as terms, almost all MedDRA preferred terms, each under an organ system (MedDRA's system organ class). The analysis counts, for each outcome below, the participants in each arm with a serious adverse event whose term belongs to that outcome. Your task is to say which outcomes each term belongs to. You see each term (lower-cased, spaces collapsed) and the organ systems it was reported under, and no counts.

## How to code a term

- Give each term **every** outcome whose definition it meets. Most terms meet none; some meet several (for example "pneumonia aspiration" meets A21 pneumonia, A22 aspiration, and A23 pneumonitis).
- Code by what the term means clinically, the way a pharmacovigilance physician building a term list would. A term meets an outcome when an event reported under it would, in the large majority of cases, be an instance of that outcome. Don't code a term to an outcome it only sometimes accompanies (for example "dyspnoea" is not respiratory failure; "fall" is not a fracture).
- Follow each definition's inclusions and exclusions. Where a definition names terms, those are examples, not a complete list: include other terms of the same meaning, including spelling variants, older MedDRA terms, and terms qualified by site, cause, or severity.
- A procedure term counts when the procedure is done almost only for that outcome (for example "cholecystectomy" for B01), never otherwise.
- Give `canonical`: the term as a MedDRA preferred term, in MedDRA's spelling (British, e.g. "anaemia", "diarrhoea", "oesophagitis") and capitalized as MedDRA writes it (first letter capital). Use it to merge terms that are the same preferred term spelled or cased differently. If a term is a lowest-level term or a free-text variant of a preferred term, give that preferred term. If you can't tell, give the term itself with its first letter capitalized.

## Outcomes

### A. Associations the VA atlas reported for GLP-1 receptor agonists against usual care

Xie, Choi and Al-Aly (Nature Medicine, 2025) named these associations in their results. Cardiometabolic outcomes (myocardial infarction, cardiac arrest, heart failure, stroke, chronic kidney disease) are left out because the large trials adjudicate them as efficacy endpoints, and many leave endpoint events out of their adverse-event tables.

| ID | Outcome | Includes | Excludes |
|---|---|---|---|
| A01 | Alcohol use disorder | alcoholism, alcohol abuse, alcohol dependence, alcohol use disorder, alcohol withdrawal syndrome, delirium tremens, alcohol poisoning, alcoholic intoxication | alcoholic liver disease, alcoholic pancreatitis, alcoholic cardiomyopathy (organ damage, not the disorder) |
| A02 | Cannabis use disorder | cannabis abuse, dependence, or use disorder; cannabinoid hyperemesis syndrome; cannabis intoxication | |
| A03 | Stimulant use disorder | cocaine, amphetamine, methamphetamine, or other stimulant abuse, dependence, use disorder, or intoxication | |
| A04 | Opioid use disorder | opioid abuse, dependence, use disorder, withdrawal, or overdose; heroin or fentanyl overdose | |
| A05 | Suicidal ideation, suicide attempt, or intentional self-harm | suicidal ideation, suicidal behaviour, suicide attempt, completed suicide, intentional self-injury, intentional overdose, self-poisoning with intent | accidental overdose |
| A06 | Bulimia | bulimia nervosa, binge eating disorder, binge-purge behaviour | anorexia nervosa, decreased appetite |
| A07 | Schizophrenia and other psychotic disorders | schizophrenia, schizoaffective disorder, psychotic disorder, acute psychosis, delusional disorder, hallucinations as a psychotic episode | delirium; hallucinations reported as a side effect without psychosis |
| A08 | Seizures | seizure, convulsion, epilepsy, status epilepticus, generalised tonic-clonic seizure, partial seizures, febrile convulsion | syncope, convulsive syncope |
| A09 | Neurocognitive disorders | dementia of any type, Alzheimer's disease, cognitive disorder, mild cognitive impairment, memory impairment, amnesia | delirium, confusional state (acute and usually from another cause) |
| A10 | Dementia | dementia of any type, Alzheimer's disease, vascular dementia, dementia with Lewy bodies, frontotemporal dementia | mild cognitive impairment |
| A11 | Coagulopathy and clotting disorders | coagulopathy, disseminated intravascular coagulation, coagulation factor deficiency, hypercoagulation, thrombophilia, haemophilia, acquired clotting disorders, abnormal clotting tests reported as a disorder (INR increased, prothrombin time prolonged) | thrombocytopenia, bleeding events, thromboses (A12) |
| A12 | Venous thromboembolism | deep vein thrombosis, pulmonary embolism, venous thrombosis of any site (portal, mesenteric, cerebral venous sinus, jugular, splenic, renal vein), thrombophlebitis, venous embolism | arterial thrombosis or embolism, superficial phlebitis without thrombosis, catheter occlusion |
| A13 | Pulmonary embolism | pulmonary embolism, pulmonary thrombosis, pulmonary infarction | |
| A14 | Deep vein thrombosis | deep vein thrombosis of any limb, iliac or femoral vein thrombosis, post-thrombotic syndrome | superficial thrombophlebitis |
| A15 | Phlebitis | phlebitis, thrombophlebitis (superficial or deep), venous inflammation | infusion site phlebitis |
| A16 | Pulmonary hypertension | pulmonary hypertension, pulmonary arterial hypertension, cor pulmonale, chronic thromboembolic pulmonary hypertension | |
| A17 | Acute kidney injury | acute kidney injury, acute renal failure, renal failure (unqualified), acute prerenal failure, prerenal failure, acute tubular necrosis, renal impairment reported as an acute event, oliguria, anuria | chronic kidney disease, end-stage renal disease, renal failure chronic, nephropathy, proteinuria |
| A18 | Bacterial infections | any infection named as bacterial or naming a bacterium (staphylococcal, streptococcal, Escherichia, Clostridium difficile, ...), and infections that are bacterial in the large majority of cases: cellulitis, erysipelas, abscesses, osteomyelitis, septic arthritis, infective endocarditis, pyelonephritis, urinary tract infection, cystitis, urosepsis, sepsis, septic shock, bacteraemia, wound infection, diabetic foot infection, gangrene (infected), necrotising fasciitis, tuberculosis, bacterial pneumonia | viral, fungal, or parasitic infections; pneumonia without a named bacterial cause; gastroenteritis without a named bacterial cause; appendicitis, cholecystitis, diverticulitis (inflammatory conditions coded under their organs) |
| A19 | Bacterial pneumonia | pneumonia bacterial, pneumonia naming a bacterium (pneumococcal, staphylococcal, Klebsiella, Legionella, Haemophilus, ...), lobar pneumonia | pneumonia with no named bacterial cause |
| A20 | Sepsis | sepsis, septic shock, septicaemia, urosepsis, bacteraemia, systemic inflammatory response syndrome from infection, sepsis of any named organism or source | localized infection alone |
| A21 | Pneumonia | pneumonia of any cause (bacterial, viral including COVID-19 pneumonia, fungal, aspiration, atypical, unspecified), bronchopneumonia, lobar pneumonia, lung infection, lower respiratory tract infection | bronchitis, upper respiratory infection, COVID-19 without pneumonia |
| A22 | Aspiration | pneumonia aspiration, aspiration pneumonitis, aspiration (of gastric contents or a foreign body into the airway) | |
| A23 | Pneumonitis | pneumonitis of any cause (aspiration, chemical, radiation, drug-induced, hypersensitivity), interstitial lung disease reported as pneumonitis, organising pneumonia | infectious pneumonia not called pneumonitis |
| A24 | Postprocedural respiratory complications | respiratory events named as postprocedural or postoperative (postoperative pneumonia, postprocedural respiratory failure, atelectasis postoperative, postoperative respiratory distress) | the same events without a procedural link |
| A25 | Pleural effusion | pleural effusion of any cause, including malignant pleural effusion, haemothorax | pneumothorax, empyema (an infection) |
| A26 | Chronic obstructive pulmonary disease | COPD, chronic obstructive pulmonary disease exacerbation, chronic bronchitis, emphysema | asthma |
| A27 | Respiratory failure | respiratory failure, acute respiratory failure, chronic respiratory failure, hypercapnic or hypoxic respiratory failure, acute respiratory distress syndrome, respiratory arrest | dyspnoea, hypoxia without failure, respiratory distress of the newborn |
| A28 | Anaemia | anaemia of any type (iron deficiency, normocytic, of chronic disease, haemolytic, aplastic, megaloblastic), haemoglobin decreased reported as an event, pancytopenia | blood loss without anaemia, thrombocytopenia alone |
| A29 | Muscle pain | myalgia, muscle pain, polymyalgia rheumatica | musculoskeletal pain not named as muscle pain, arthralgia, back pain, rhabdomyolysis, myositis |
| A30 | Hepatic failure | hepatic failure, acute hepatic failure, acute-on-chronic liver failure, hepatic encephalopathy, hepatorenal syndrome, liver failure from any cause | hepatitis or raised enzymes without failure, cirrhosis without failure |
| A31 | Inflammatory bowel disease | Crohn's disease, ulcerative colitis, inflammatory bowel disease, colitis ulcerative, proctitis ulcerative | infectious colitis, ischaemic colitis, microscopic colitis, colitis unspecified |
| A32 | Liver cancer | hepatocellular carcinoma, hepatic cancer, liver carcinoma, intrahepatic cholangiocarcinoma, hepatoblastoma | metastases to the liver, benign liver tumours, extrahepatic bile duct cancer |
| A33 | Abdominal pain | abdominal pain, abdominal pain upper or lower, abdominal discomfort, abdominal tenderness, epigastric pain | pain named for a specific organ diagnosis (e.g. biliary colic, renal colic) |
| A34 | Nausea and vomiting | nausea, vomiting, retching, cyclic vomiting syndrome, hyperemesis outside pregnancy | vomiting of pregnancy, cannabinoid hyperemesis syndrome (A02 only) |
| A35 | Gastro-oesophageal reflux disease | gastro-oesophageal reflux disease, reflux oesophagitis, oesophagitis, Barrett's oesophagus | dyspepsia |
| A36 | Gastritis | gastritis of any type (erosive, atrophic, haemorrhagic, Helicobacter), gastroduodenitis, duodenitis | peptic ulcer without gastritis |
| A37 | Noninfectious gastroenteritis or colitis | gastroenteritis noninfective, enteritis, colitis (unspecified, microscopic, ischaemic), enterocolitis, ileitis | gastroenteritis named as infectious or viral, infectious diarrhoea, inflammatory bowel disease (A31) |
| A38 | Gastroparesis | gastroparesis, delayed gastric emptying, gastric stasis, impaired gastric emptying | |
| A39 | Diverticular disease | diverticulitis, diverticulum, diverticulosis, diverticular perforation, diverticular haemorrhage, diverticulitis intestinal haemorrhagic | Meckel's diverticulum |
| A40 | Hypotension | hypotension, orthostatic hypotension, blood pressure decreased | shock of any cause |
| A41 | Syncope | syncope, presyncope, loss of consciousness, vasovagal syncope | seizure, coma |
| A42 | Sleep disturbances | insomnia, sleep disorder, sleep apnoea syndrome, obstructive sleep apnoea, hypersomnia, parasomnia, abnormal dreams, circadian rhythm sleep disorder | somnolence from drugs or illness |
| A43 | Headache | headache, migraine, tension headache, cluster headache | headache named for a structural cause (subarachnoid haemorrhage) |
| A44 | Arthritis | arthritis, osteoarthritis of any joint, arthropathy, rheumatoid arthritis, polyarthritis, psoriatic arthropathy, spondyloarthropathy, gouty arthritis, gout | septic arthritis, joint injury |
| A45 | Arthralgia | arthralgia, joint pain, joint swelling, joint effusion | |
| A46 | Tendinitis and synovitis | tendonitis, tenosynovitis, synovitis, bursitis, enthesopathy, tendon disorder, trigger finger, rotator cuff syndrome, tendon rupture | |
| A47 | Interstitial nephritis | tubulointerstitial nephritis, interstitial nephritis, nephritis interstitial | glomerulonephritis |
| A48 | Kidney stones | nephrolithiasis, urolithiasis, ureterolithiasis, calculus urinary, calculus ureteric, renal colic, kidney stone, bladder stone | |
| A49 | Acute pancreatitis | pancreatitis, pancreatitis acute, pancreatitis necrotising, pancreatitis haemorrhagic, oedematous pancreatitis, pancreatitis relapsing | chronic pancreatitis, pancreatic enzymes increased |

### B. Other questions asked of these drugs

| ID | Outcome | Includes | Excludes |
|---|---|---|---|
| B01 | Gallbladder and biliary disease | cholelithiasis, cholecystitis (acute or chronic), biliary colic, choledocholithiasis, cholangitis, gallbladder disorder, cholecystectomy, biliary obstruction from stones, gallstone pancreatitis | biliary cancer, primary biliary cholangitis |
| B02 | Intestinal obstruction or ileus | intestinal obstruction, small or large intestinal obstruction, ileus, ileus paralytic, subileus, volvulus, intussusception, bowel obstruction | constipation, faecaloma |
| B03 | Ischaemic optic neuropathy | optic ischaemic neuropathy, non-arteritic anterior ischaemic optic neuropathy, arteritic ischaemic optic neuropathy | other optic neuropathies, retinal vascular occlusion |
| B04 | Diabetic retinopathy complications | diabetic retinopathy, proliferative retinopathy, vitreous haemorrhage, diabetic macular oedema, retinal neovascularisation, retinal detachment from diabetic disease | cataract, glaucoma |
| B05 | Thyroid cancer | thyroid cancer of any type (papillary, follicular, medullary, anaplastic), thyroid neoplasm malignant | benign thyroid nodules, goitre |
| B06 | Any malignant neoplasm | every malignant neoplasm of any site, including haematological malignancies, metastases, and skin cancers | benign neoplasms, neoplasms not stated as malignant (polyps, cysts, "neoplasm" unspecified), precancerous conditions |
| B07 | Obesity-associated cancers | the thirteen cancers IARC links to excess body fat: oesophageal adenocarcinoma, gastric cancer (cardia; code gastric cancer of unstated site here too), colorectal cancer, liver cancer, gallbladder cancer, pancreatic cancer, kidney (renal cell) cancer, breast cancer, endometrial (uterine) cancer, ovarian cancer, thyroid cancer, multiple myeloma, meningioma | other cancers, oesophageal squamous cell carcinoma (meningioma counts whether or not it is called malignant) |
| B08 | Depression | depression, major depression, depressed mood, depressive symptom, adjustment disorder with depressed mood, persistent depressive disorder | bipolar disorder, suicidal ideation alone (A05) |
| B09 | Fractures | fracture of any bone, from any cause | dislocation without fracture |
| B10 | Falls | fall | |
| B11 | Pancreatic cancer | pancreatic carcinoma, adenocarcinoma of the pancreas, pancreatic neuroendocrine tumour (malignant), pancreatic neoplasm malignant | benign pancreatic cysts, intraductal papillary mucinous neoplasm unless called malignant |

## Output

A JSON array, one object per input term, in the order given:

```json
{"term": "pneumonia aspiration", "canonical": "Pneumonia aspiration", "outcomes": ["A21", "A22", "A23"]}
```

`outcomes` is an empty array when the term meets none.