You are on page 1of 10

A.N.R.

S
ANRS scale to grade the severity of adverse events in adults Version n° 1.0 4 November 2008
(Translation of the French version n°6 9 September 2003) This severity scale is a working guide intended to harmonise evaluation and grading practices for symptomatology in ANRS biomedical research protocols. In practice, the items evaluated are grouped according to the system taking the form of a nonexhaustive symptomatic table (and not a classification of pathologies). Our choices focus on the most frequently observed clinical and biological signs or those whose monitoring is essential to ensure the protection of the subjects participating in the research. For abnormalities NOT found elsewhere on the Table, refer to the scale below to estimate grade of severity: Mild or transient discomfort, without limitation of normal daily activities; no medical intervention or corrective treatment required. Mild to moderate limitation of normal daily activities; minimal medical intervention or corrective treatment required. Marked limitation of normal daily activities; medical intervention and corrective treatment required, possible hospitalisation. Severe limitation of normal daily activities; medical intervention and corrective treatment required, almost always in a hospital setting. Upper Limit of Normal Red Blood Cells Forced Expiratory Volume in one second Electromyogram Corresponds to Quick time (sec) activated Partial Thromboplastin Time

GRADE 1 GRADE 2 GRADE 3 GRADE 4

Mild Moderate Severe Life-threatening

Abbreviations used in the table: : ULN : RBC : FEV1 : EMG : Prothrombin Time (%) : aPTT

This document is the exclusive property of the ANRS and must not be modified or published without the authors’ prior consent. Any use is subject to prior consent from the ANRS. Any questions should be addressed to pharmacovigilance@anrs.fr. Please note that this scale was devised for use in HIV, HCV or HBV related pathologies.

Page 1 of 10

0 x ULN > 3.ANRS scale to grade the severity of adverse events in adults (version no 1.50 – 5.33 – 3.00 – 10.60 – 13.0 x ULN with acute abdominal pain and/or imaging indicating acute pancreatitis.0 x ULN 1.0 – 1.0 x ULN ≥1.50 – 5.0 – 9.0 x ULN with abdominal pain and signs of shock.0 x ULN > 5.25 – 2.25 – 2.25 – 2.00 – 10.50 – 8.34 > 5.50 – 5.50 x ULN > 2.0 x ULN > 10.00 – 10.0 x ULN > 10.00 – 10.25 – 2.75 > 2.0 x ULN > 10. > 5.66 – 2.0 x ULN > 13.0 x ULN > 5.00 – 10.0 x ULN 1.25 – 2.50 – 5.0 x ULN 1.0 x ULN 8.50 x ULN / >ULN –7.34 – 12.50 – 5.0 x ULN > 5.50 – 5.0 4 November 2008) GRADES 1 2 3 4 5 6 Haemoglobin (g/dl) Leucocytes (/mm3) Neutrophils (/mm3) Platelets (/mm3) Prothrombin Time (%) aPTT GRADE 1 Mild 8.50 x ULN > 2.70 >10.99 2 000 – 2 999 750 – 999 50 000 – 74 999 GRADE 3 Severe 6.50 – 5.70 >12.50 x ULN > 2.5 – 6.75 – 10.0 x ULN > 5.25 – 2.0 x ULN > 10.0 x ULN GRADE 4 Life-threatening < 6.0 x ULN 13 CPK (UI/l) 14 Hypertriglyceridaemia (mmol/l) 15 Hypercholesterolaemia (mmol/l) 1.92 Page 2 of 10 .0 x ULN Lipid status 4.50 x ULN > 2.99 1 000 – 1 999 500 – 749 20 000 – 49 999 20 – < 45 > 2.59 >7.0 – 7.66 x ULN GRADE 2 Moderate HAEMATOLOGY 7.92 > 10.25 – 2.0x ULN > 3.0 x ULN 7 8 9 10 11 12 AST (SGOT) (UI/l) ALT (SGPT) (UI/l) GAMMA GT (UI/l) Alkaline phosphatase (UI/l) Hyperbilirubinaemia (µmol/l) Amylasaemia (UI/l) / Lipasaemia (UI/l)/ Pancreatitis 45 – ≤ 70 > 1.0 x ULN 1.50 x ULN > 2.50 x ULN > 2.5 < 1 000 < 500 <20 000 or generalized petechiae < 20 > 3.4 3 000 – 3 900 1 000 – 1 500 75 000 – 99 000 / 1.00 – 10. > 10.33 x ULN BIOCHEMISTRY Hepatic and pancreatic biochemistry 1.

38 1.0 – 3. 4.25 – 2.1 – 6.5 >7.4 > 5.5 6.5 – 1.0*** 16 17 18 19 20 21 22 23 Hyponatraemia (mEq/l) Hypernatraemia (mEq/l) Hypokalaemia (mEq/l) Hyperkalaemia (mEq/l) Bicarbonate (mEq/l or mmol/l) Creatininaemia (µmol/l) Blood Urea Nitrogen (UI/l) Hypocalcaemia (mmol/l) Electrolytes / Evaluation of renal function / Metabolism 130 – 135 123 – 129 116 – 122 146 – 150 151 – 157 158 – 165 3.5 x ULN 2.5 without ketosis.4 2.6 6.50 > 3.0 – 10.0 x ULN 1.5 – 2.1 – 7.7 See diabetes Item no.0 – 2.13 1.50 x ULN > 1.0 x ULN 3.5 3.25 – 2.0 – 4.99** 24 Hypercalcaemia (mmol/l) 25 Hypophosphataemia (mg/dl) 26 Hyperuricaemia (µmol/l) 27 Hypoglycaemia (mmol/l) 28 Hyperglycaemia (mmol/l) 29 Hyperlactataemia (mmol/l) (venous blood sample) 30 Proteinuria (dipstick) 31 Haematuria.88 – 3.38 <1.87 2. Lactataemia – GRADE 1: a confirmatory test is necessary within 8 to 10 days Lactataemia – GRADE 2.50 – 3.50 – 1. 3: a confirmatory test is necessary within 24 hours.0 6.0 x ULN 5.6 – 5.99 10.0 – 1.0 – 16.0 – 2.0 x ULN 1.0 4 November 2008) GRADE 1 GRADES Mild GRADE 2 Moderate GRADE 3 Severe GRADE 4 Life-threatening <116 >165 <2. 52 (grade 4) ≥ 5.0 6.10 1.6 – 6.1 – 10 x ULN 1.75 – 1.0 > 10.7 5.99* 2. Page 3 of 10 . Lactataemia – GRADE 4: a confirmation test is necessary immediately.9 > 2.65 – 2.0 20.0 – 24.0 – 1.74 2.6 – 7.7 – 2.0 – 6.1 > 16.0 15.0 > 7.0 2.2 – 3.4 1.0 – 14.0 x ULN 2.2 – 3.0 – 5.0 x ULN < 1. * ** *** + ≥ 80 RBC/µl (dipstick).1 – 3. ≥ +++ Macroscopic with or without clots. ++ ≥ 200 RBC/µl (dipstick). Nephrotic syndrome Obstructive or requiring a blood transfusion.0 x ULN or dialysis required > 10 x ULN < 1.0 x ULN > 3.14 – 3.1 2.0 < 10.8 – 3.ANRS scale to grade the severity of adverse events in adults (version no 1.99 1.94 1.95 – 2.99** Urinalysis 3.0 – 19.

diarrhoea > 1 week. Vomiting. 3 – 4 stools / day. days. Moderate abdominal pain. Dysphagia. normal diet.ANRS scale to grade the severity of adverse events in adults (version no 1. food intake possible. 5-7 stools / day. Gastro-intestinal/hepatic/pancreatic abnormalities Transient. diarrhoea ≤ 1 week. Pyrosis occurring at least once Pyrosis occurring less than Pyrosis occurring at least once Food intolerance and vomiting a week but not relieved by once a week a week but relieved by PPIs* PPIs* *PPIs: proton pump inhibitors Page 4 of 10 . duration ≤ 1 week. Transient.0 4 November 2008) GRADE 1 GRADES Mild GRADE 2 Moderate GRADE 3 Severe GRADE 4 Life-threatening 32 33 34 35 36 37 Nausea. Meteorism. hypovolemic shock. Persistent. Meteorism with vomiting or / 78 h without stools. perfusion. Constipation. Hospitalization for 2 – 3 episodes / day or 4 – 5 episodes / day or Orthostatic hypotension. Inability to swallow solids. hospital treatment. Hypovolemic shock. days. Bloody stools. Diarrhoea. Perfusion required. Treatment required. Mild discomfort when Difficulty in swallowing but Inability to swallow liquids. Requiring disimpaction or occlusion. swallowing. perfusion required. Hospitalization required. perfusion. > 7 stools/day or requiring Hospitalization. duration > 1 week. Transient: Repeated: Solid/liquid vomiting for 24 h. Restricted diet for less than 3 Restricted diet for more than 3 Liquid only diet. Oesophagitis.

Not requiring (difficulty in climbing stairs or analgesic treatment. rising from a sitting position). Muscular abnormalities GRADE 3 Severe Persistent under bronchodilation. Dyspnoea requiring respiratory assistance. Improvement under bronchodilation FEV1 50 % . no treatment. : Morphine. dextropropoxyphene). Dyspnoea 40 Myalgia (excluding injection site). FEV1 25 % .ANRS scale to grade the severity of adverse events in adults (version no 1. electromyographical (EMG) or histological (muscular biopsy) abnormalities. * Level I analgesics * Level II analgesics * Level III analgesics : Peripheral analgesics (paracetamol and/or salicylics or non-steroid anti-inflammatory drugs) . Paraclinical confirmation required (biology.< 50 %. 38 39 Bronchospasm. FEV1 < 25 % intubation. 2 – Predominance of Mild myalgia for less than 4 difficulties upon exertion weeks. Paraclinical confirmation recommended (CPK. Page 5 of 10 . 2 – Muscular weakness making walking impossible without assistance. Presence of one of the following symptoms: 1 – Severe myalgia not related to exertion requiring treatment with level II/III* analgesics. Optional confirmation through the identification of biological (CPK). morphinic agonists-antagonists (buprenorphine. : Weak opiates (codeine. Presence of one of the following symptoms: 1 – Mild to moderate myalgia for more than 4 weeks and/or which may require treatment with level 1* analgesics.< 80 %. EMG and/or muscular biopsy). 2 – Assistance required for walking and normal daily activities. 4 – Acute rhabdomyolysis with electrolytic disturbances and renal insufficiency. Dyspnoea at rest. nalbuphine) . 3 – Acute rhabdomyolysis with muscular necrosis and oedema.0 4 November 2008) GRADES GRADE 1 Mild Transient. GRADE 2 Moderate Respiratory abnormalities Permanent. Dyspnoea during normal daily activities.< 70 %. GRADE 4 Life-threatening Cyanosis. Can walk without assistance. Presence of one of the following symptoms: 1 – Moderate to severe myalgia for more than 4 weeks requiring treatment with level I/II* analgesics. EMG and/or muscular biopsy). FEV1 70 % . Dyspnoea upon exertion.

Transient or permanent. preinfarction syndrome. durable but corrected No treatment. Deep vein thrombosis and/or pulmonary embolism. Dysrhythmia requiring hospitalization. Anticoagulant treatment. with liquid intake per os. no treatment. 42 Perfusion required. symptomatic or asymptomatic. Hospitalization. Decreased systolic blood pressure Decreased systolic blood pressure ≤ 20 mmHg in orthostatic position. 43 Recurrent.0 4 November 2008) GRADES GRADE 1 Mild GRADE 2 Moderate Cardiovascular abnormalities GRADE 3 Severe GRADE 4 Life-threatening 41 Arterial hypertension. Treatment required. Hypovolemic shock requiring hospitalization. / 48 Peripheral arterial embolism. unstable angina. Pulmonary embolism. / Transient Ischemic Attack (regressive focal neurological syndrome within 24 h). Permanent. Treatment required and Hospitalization and intervention intervention deemed necessary for required. Appearance of angina upon exertion. / Deep vein thrombosis. persistent or symptomatic cardiac rhythm disorders. the time being. torsade de pointes) Myocardial infarction. hospitalization to be considered. Adapted treatment. Adequate hospitalization and treatment. Ventricular cardiac rhythm disorders. syncope. / Atypical pain under exploration. Chance discovery of a small effusion during ultrasound scan Moderate effusion with few Moderate or significant symptomatic effusion Tamponade. No treatment or but without tamponade. Peripheral arterial embolism. Cerebrovascular accident nonregressive within 24 h. / >500ms 45 Cardiac ischaemia. / Isolated ventricular extrasystoles. / / 49 / / . symptoms. Increased blood pressure > 20 Increased blood pressure ≤ 20 mmHg and systolic BP 140-159 or mmHg and systolic BP 160-179 or diastolic BP 100-109. > 20 mmHg. >500 ms with clinical symptoms (ventricular rhythm disorders. Man: >450 and < 500 ms Woman: >470 and <500 ms Permanent. diastolic BP 90-99. Systolic BP ≥ 180 or diastolic BP > 110 Malignant or accelerated arterial hypertension. Prolongation of the 44 QT interval. Page 6 of 10 47 Stroke.ANRS scale to grade the severity of adverse events in adults (version no 1. controlled with treatment. Hospitalization to be considered. Orthostatic hypotension. 46 Pericarditis.

GRADE 3 Severe GRADE 4 Life-threatening 50 Hyperthyroidism. Moderate. Stevens-Johnson). with or without cutaneous symptoms. 54 Symptoms of immediate hypersensitivity. Severe hypothyroidism with multiple clinical symptoms.ANRS scale to grade the severity of adverse events in adults (version no 1. Anaphylactic shock. Infraclinical hypothyroidism. Thyrotoxic crisis and/or cardiac insufficiency. 51 Hypothyroidism. Insulin therapy required. Palpable purpura Febrile erythrodermia. Normal free T3 and T4. with or without pruritis. Quincke’s oedema.8 mmol/l without acidosis). free T4. Moderate pruritis. Ketoacidosis or hyperosmolarity (>27. whether or not associated Polymorphous erythaema. Hospitalization to be considered.1 and 7 mmol/l. Page 7 of 10 . Urgent treatment. non-complicated thyrotoxicosis. Treatment TSH but <12 mU/l. Extended maculopapular eruption. Low TSH. Normal required. Myopathy. Cutaneous abnormalities Myxoedematous coma.0 4 November 2008) GRADES GRADE 1 Mild GRADE 2 Moderate Endocrine abnormalities Infraclinical hyperthyroidism. Special diet required. Moderate fasting hyperglycaemia between 6. Cardiac arrhythmia. No immediate treatment required. ulcerations. Malignant exophtalmia.5 mmol/l on an empty stomach. with or without clinical symptoms. Fasting glycaemia: > 7 mmol/l. Increased Simple hypothyroidism without complications. with other signs indicative of Small-size cutaneous or mucous hypersensitivity. Fasting glycaemia:>16. / Acute localised urticaria. Giant urticaria. Cutaneous necrosis requiring surgical excision. 52 Diabetes/hyperglycaemia. possibly supplemented with oral antidiabetics. Erythaema. (suggestive of vasculitis). Treatment required. Any blistering cutaneous and/or mucosal lesions Extended papulovesicular or (Lyell or oozing eruption. 53 Cutaneous and/or mucosal eruptions.

ANRS scale to grade the severity of adverse events in adults (version no 1. reflex changes. Requiring at least level II* Not responsive to level III* Requiring level I* analgesics. level II* analgesics. mild pain. morphinic agonists-antagonists (buprenorphine. Intermittent. or dysarthria. Sensory loss. 56 57 58 Psychiatric disorders. Subjective feeling of weakness without objective impairment. restricted activity moderate intensity. dextropropoxyphene). : Morphine. activities. Paraesthesia. Difficulty controlling movement. including Anxiety requiring treatment or depressive episode requiring suicidal ideation. involving the trunk and four limbs. obnubilation. limitation limitation of normal daily dependence. moderate depression. Extensive sensory loss Moderate sensory loss. Unbearable pain resulting in Paresthesia.0 4 November 2008) GRADES GRADE 1 Mild GRADE 2 Moderate Neurological abnormalities Sleep-wake cycle Sleep-wake cycle modification or insomnia requiring treatment or disorganisation not responding to treatment. regardless of mode and distribution (focal or symmetric). Paraesthesia. Minor anxiety. treatment. III* analgesics. GRADE 3 Severe GRADE 4 Life-threatening 55 Wakefulness / sleep disorders. Distal motor deficiency. Diurnal somnolence and/or difficulty falling asleep and/or night time awakening. : Weak opiates (codeine. Minor attention and concentration impairment. 59 Motor deficiency. hallucinatory delusion. permanent pain of Paraesthesia. analgesics. 60 61 * Level I analgesics * Level II analgesics * Level III analgesics : Peripheral analgesics (paracetamol and/or salicylics or non-steroid anti-inflammatory drugs) . no treatment. analgesics. Page 8 of 10 . Marked motor deficiency Confined to bed or a wheelchair moderate functional impairment or interfering with normal daily because of motor deficiency. Occasional clumsiness. Mild sensory loss. nalbuphine) . mental activity decreased. coma and/or with temporal disorientation. Severe sensory loss. no reflex changes. requiring at least despite administration of level I* analgesics. manic state. requiring level severe intensity. of normal daily activities. no treatment. Total dysmetria. Tremor or dyskinaesia or Upper or lower limbs ataxia or Inability to stand up. permanent pain of disability. convulsion. Acute psychosis requiring Major anxiety or confirmed hospitalization. change in dream content. activities. mild coordination difficulties. Cephalalgia. Dreamlike confusional Obvious confusional syndrome syndrome. moderate abnormal movements.

Arthralgia. Pain not requiring treatment. Normal daily activities reduced by more than 50%. Glaucoma. Conjunctival hyperaemia. / GRADE 3 Severe GRADE 4 Life-threatening 64 Fatigue.0 4 November 2008) GRADES GRADE 1 Mild GRADE 2 Moderate Miscellaneous 62 63 Fever (oral temperature. > 40. 39 – 39. 66 Ocular disorders. 37. °C) for more than 12 h. Marked arthritis with or without effusion or with severe functional impairment. Severe pain.5 Obstructive syndrome.5 Colic requiring medical treatment.6 – 40. Moderate pain.9 Spontaneous regression of symptoms. with or without articular effusion or with moderate functional impairment. Conjunctivitis. cannot work for more than 48 h. Uveitis. Arthralgia. does not disappear spontaneously. Assistance required for normal daily activities. / Page 9 of 10 . 39.7 – 38.5 / Unable to care for self. Normal daily activities reduced by 25 – 50 % for more than 48 h. Decreased visual acuity. Normal daily activities reduced by less than 25% for less than 48 h. 65 Arthritis / Arthralgia.ANRS scale to grade the severity of adverse events in adults (version no 1. Renal colic.

GRADE 2 Moderate ≥ 15 x 15 cm. nodule (induration). Pain inducing partial mobility impairment.ANRS vaccine trials. no limitation of movements. Pain. Mild.0 GRADES 1 Erythaema. GRADE 4 Life-threatening Skin necrosis 2 / Page 10 of 10 . 4 November 2008) GRADE 1 Mild < 15 x 15 cm. oedema. Pain inducing functional impotence. GRADE 3 Severe Ulceration or superinfection or superficial phlebitis. ANRS scale to grade the severity of adverse events in adults (version no 1. functional impairment.