Daids Ae Grading Table v2 Nov2014

Division of AIDS (DAIDS) Table for
Grading the Severity of Adult and

Pediatric Adverse Events
Version 2.0
November 2014
Division of AIDS
National Institute of Allergy and Infectious Diseases
National Institutes of Health
US Department of Health and Human Services
Table of Contents
Glossary and Acronyms .................................................................................................................. 1
Introduction ..................................................................................................................................... 3
Instructions for Use ......................................................................................................................... 4
Major Clinical Conditions............................................................................................................... 7
Cardiovascular .......................................................................................................................... 7
Dermatologic............................................................................................................................. 9
Endocrine and Metabolic ........................................................................................................ 10
Gastrointestinal ....................................................................................................................... 11
Musculoskeletal ...................................................................................................................... 13
Neurologic............................................................................................................................... 14
Pregnancy, Puerperium, and Perinatal .................................................................................... 16
Psychiatric ............................................................................................................................... 17
Respiratory .............................................................................................................................. 18
Sensory.................................................................................................................................... 19
Systemic .................................................................................................................................. 20
Urinary .................................................................................................................................... 22
Site Reactions to Injections and Infusions .................................................................................... 23
Laboratory Values ......................................................................................................................... 24
Chemistries ............................................................................................................................. 24
Hematology ............................................................................................................................. 27
Urinalysis ................................................................................................................................ 29
Appendix A. Total Bilirubin Table for Term and Preterm Neonates .......................................... 30
Glossary and Acronyms
AE Adverse event; Any unfavorable and unintended sign (including an
abnormal laboratory finding), symptom, or disease temporally
associated with the use of a medical treatment or procedure regardless
of whether it is considered related to the medical treatment or
procedure.
ALT (SGPT) Alanine aminotransferase (serum glutamic pyruvic transaminase)
ANC Absolute neutrophil count
AST (SGOT) Aspartate aminotransferase (serum glutamic-oxaloacetic transaminase)
AV Atrioventricular
Basic Self-care Functions Adult
Activities such as bathing, dressing, toileting, transfer or movement,
continence, and feeding.
Young Children
Activities that are age and culturally appropriate, such as feeding one’s
self with culturally appropriate eating implements.
BMI z-score Body mass index z- score; A body reference norm. Specifically, the
number of standard deviations a participant's BMI differs from the
average BMI for their age, sex, and ethnicity.
BMD t-score Bone mineral density t-score; The number of standard deviations above
or below the mean bone mineral density of a healthy 30 year old adult
of the same sex and ethnicity as the participant.
BMD z-score Bone mineral density z-score; The number of standard deviations a
participant's BMD differs from the average BMD for their age, sex, and
ethnicity.
BPAP Bilevel positive airway pressure; A mode used during noninvasive
positive pressure ventilation.
Chemical Pregnancy A pregnancy in which a positive pregnancy test is followed by a
negative pregnancy test without evidence of a clinical pregnancy loss.
CNS Central nervous system
CPAP Continuous positive airway pressure
DAERS DAIDS Adverse Experience Reporting System; An internet-based
system developed for clinical research sites to report Expedited
Adverse Events (EAEs) to DAIDS. It facilitates timely EAE report
submission and serves as a centralized location for accessing and
processing EAE information for reporting purposes.
Disability A substantial disruption of a person’s ability to conduct normal life
functions.
ECG Electrocardiogram
eGFR Estimated glomerular filtration rate
Hospitalization Does not include the following hospital admissions: under 24 hours,
unrelated to an adverse event (e.g., for labor and delivery, cosmetic
surgery, social or administrative for temporary placement [for lack of a
place to sleep]), protocol-specified, and for diagnosis or therapy of a
condition that existed before the receipt of a study agent and which has
not increased in severity or frequency.
INR International normalized ratio
DAIDS AE Grading Table Version 2.0- November 2014

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Glossary and Acronyms
Intervention Medical, surgical, or other procedures recommended or provided by a
healthcare professional for the treatment of an adverse event.
IV Intravenous
IVIG Intravenous immune globulin
LDL Low density lipoprotein
LLN Lower limit of normal
Life-threatening AE Any adverse event that places the participant, in the view of the
investigator, at immediate risk of death from the reaction when it
occurred (i.e., it does not include a reaction that would have caused
death if it had occurred in a more severe form).
NA Not applicable
Participant ID The identification number assigned to a study participant which is used
to track study-related documentation, including any reported AEs.
PR Interval The interval between the beginning of the P wave and the beginning of
the QRS complex of an electrocardiogram that represents the time
between the beginning of the contraction of the atria and the beginning
of the contraction of the ventricles.
PT Prothrombin time
PTT Partial thromboplastin time
QTc Interval The measure of time between the onset of ventricular depolarization
and completion of ventricular repolarization corrected for ventricular
rate.
RBC Red blood cell
SI Standard international unit
ULN Upper limit of normal
Usual Social & Functional Activities Activities which adults and children perform on a routine basis and
those which are part of regular activities of daily living, for example:
Adults
Adaptive tasks and desirable activities, such as going to work,
shopping, cooking, use of transportation, or pursuing a hobby.
Young Children
Activities that are age and culturally appropriate, such as social
interactions, play activities, or learning tasks.
WBC White blood cell
WHO World Health Organization
WNL Within normal limits

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Introduction
The Division of AIDS (DAIDS) oversees clinical trials throughout the world which it sponsors
and supports. The clinical trials evaluate the safety and efficacy of therapeutic products,
vaccines, and other preventive modalities. Adverse event (AE) data collected during these
clinical trials form the basis for subsequent safety and efficacy analyses of pharmaceutical
products and medical devices. Incorrect and inconsistent AE severity grading can lead to
inaccurate data analyses and interpretation, which in turn can impact the safety and well-being of
clinical trial participants and future patients using pharmaceutical products.
The DAIDS AE grading table is a shared tool for assessing the severity of AEs (including
clinical and laboratory abnormalities) in participants enrolled in clinical trials. Over the years as
scientific knowledge and experience have expanded, revisions to the DAIDS AE grading table
have become necessary.
The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse
Events, Version 2.0 replaces the grading table published in 2004 and updated in 2009. In version
2.0, AEs not previously included, but which now are deemed medically important events, are
included while other AEs have been removed. Some AE severity grading descriptions have been
revised to more appropriately reflect the presentation of these events in clinical settings and their
impact on clinical trials. For example, DAIDS performed an extensive literature search and
reviews of select DAIDS clinical trial data in revising certain hematology parameters (i.e.,
hemoglobin, white cell counts, and absolute neutrophil counts). DAIDS also took into
consideration the U.S. Food and Drug Administration’s guidance regarding the use of local
laboratory reference values and ethnic differences among certain healthy adolescent and adult
populations in defining parameter limits. Finally, the revised DAIDS AE grading table also
contains an updated glossary and acronyms section, an expanded instructions for use section, and
an appendix that provides more age-specific information for an AE of concern to DAIDS.
DAIDS is grateful to the DAIDS Grading Table Working Group, numerous government and
non-government affiliated medical subject matter experts and reviewers who were instrumental
in the revision of the DAIDS AE grading table.

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Instructions for Use
General Considerations
The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse
Events, Version 2.0 consists of parameters, or AEs, with severity grading guidance that are to be
used in DAIDS clinical trials for safety data reporting to maintain accuracy and consistency in
the evaluation of AEs. The term “severe” is not the same as the term “serious” in classifying
AEs. The severity of a specific event describes its intensity, and it is the intensity which is
graded. Seriousness, which is not graded, relates to an outcome of an AE and is a regulatory
definition.
Clinical sites are encouraged to report parameters in the DAIDS AE grading table as they are
written to maintain data consistency across clinical trials. However, since some parameters can
be reported with more specificity, clinical sites are encouraged to report parameters that convey
additional clinical information. For example, diarrhea could be reported as neonatal diarrhea;
seizures, as febrile seizures; and pain, as jaw pain.
The DAIDS AE grading table provides an AE severity grading scale ranging from grades 1 to 5
with descriptions for each AE based on the following general guidelines:
• Grade 1 indicates a mild event
• Grade 2 indicates a moderate event
• Grade 3 indicates a severe event
• Grade 4 indicates a potentially life-threatening event
• Grade 5 indicates death (Note: This grade is not specifically listed on each page of the
grading table).
Other points to consider include:

• Use parameters defined by age and sex values as applicable.
• Male and female sex are defined as sex at birth.
• Unless noted, laboratory values are for term neonates. Preterm neonates should be assessed
using local laboratory normal ranges.
• Where applicable, Standard International (SI) units are included in italics.
Selecting and Reporting a Primary AE Term

When selecting a primary AE term to report, sites should select the term that best describes what
occurred to the participant. For example, a participant may present with itching, urticaria,
flushing, angioedema of the face, and dyspnea. If the underlying diagnosis is determined to be
an acute allergic reaction, sites should report “Acute Allergic Reaction” as the primary AE term.
Primary AE terms should be reported using the DAIDS Adverse Experience Reporting System
(DAERS) only if they meet expedited reporting criteria. However, all primary AE terms should
be reported using protocol-specific case report forms (CRFs). Because the reported information
is stored in different databases (i.e., safety and clinical), sites should report primary AE terms
using the same terminology for data consistency.

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When reporting using DAERS, other clinically significant events associated with a primary AE
term that more fully describe the nature, severity, or complications of the primary AE term
should be entered in the “Other Events” section. However, the severity grade for these events
must be lower than or equal to the severity grade of the primary AE term. In the example above,
dyspnea and angioedema of the face may be entered in the “Other Events” section, because they
are more descriptive and provide additional information on the severity of the acute allergic
reaction. However, their severity grades must be lower than or equal to the severity grade of the
primary AE term of “Acute Allergic Reaction”.
Differences exist in the reporting and recording of information (e.g., signs and symptoms,
clinically significant events) in DAERS and CRFs. Therefore, sites should refer to their
protocols and CRF requirements for further instructions.
Grading Adult and Pediatric AEs

When a single parameter is not appropriate for grading an AE in both adult and pediatric
populations, separate parameters with specified age ranges are provided. If no distinction
between adult and pediatric populations has been made, the listed parameter should be used for
grading an AE in both populations.
Reporting Pregnancy Outcomes

In the Pregnancy, Puerperium, and Perinatal section, all parameters are pregnancy outcomes
and should be reported using the mother's participant ID. If an infant is not enrolled in the same
study as the mother, any identified birth defects should be reported using the mother's participant
ID. However, if an infant is enrolled in the same study as the mother or in another study, any
identified birth defects should be reported using the infant's participant ID. Sites should refer to
the applicable network standards for reporting abnormal pregnancy outcomes on the CRFs.
Determining Severity Grade for Parameters between Grades

If the severity of an AE could fall in either one of two grades (i.e., the severity of an AE could be
either grade 2 or grade 3), sites should select the higher of the two grades.
Laboratory Values
General. An asymptomatic, abnormal laboratory finding without an accompanying AE should
not be reported to DAIDS in an expedited timeframe unless it meets protocol-specific reporting
requirements. Sites should refer to the applicable network standards for reporting abnormal
laboratory findings on the CRFs.
Values below Grade 1. Any laboratory value that is between the ULN and grade 1 (for high
values) or the LLN and grade 1 (for low values) should not be graded or reported as an AE.
Sites should consult the Manual for Expedited Reporting of Adverse Events to DAIDS, Version
2.0 and their protocol when making an assessment of the need to report an AE.
Overlap of Local Laboratory Normal Values with Grading Table Ranges. When local laboratory
normal values fall within grading table laboratory ranges, the severity grading is based on the
ranges in the grading table unless there is a protocol-specific grading criterion for the laboratory

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value. For example, “Magnesium, Low" has a grade 1 range of 1.2 to < 1.4 mEq/L, while a
particular laboratory’s normal range for magnesium may be 1.3 to 2.8 mEq/L. If a study
participant’s magnesium laboratory value is 1.3 mEq/L, the laboratory value should be graded as
grade 1.
Appendix Usage
Appendix A takes priority over the main grading table in all assessments of total bilirubin for
term and preterm neonates.
Using Addenda 1-3: Grading Tables Used in Microbicide Studies

In protocols involving topical application of products to the female and male genital tracts or
rectum, strong consideration should be given to using Addenda 1-3 (see below) as the primary
grading tables for these areas. Although these grading tables are used specifically in microbicide
studies, they may be used in other protocols as adjuncts to the main grading table (i.e., the
Division of AIDS (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events,
Version 2.0). It should be clearly stated in a protocol which addendum is being used as the
primary grading table (and thus takes precedence over the main grading table) and which
addendum is being used in a complementary fashion.
• Addendum 1 – Female Genital Grading Table for Use in Microbicide Studies – PDF
• Addendum 2 – Male Genital Grading Table for Use in Microbicide Studies – PDF
• Addendum 3 – Rectal Grading Table for Use in Microbicide Studies – PDF
Estimating Severity Grade for Parameters Not Identified in the Grading Table
The functional table below should be used to grade the severity of an AE that is not specifically
identified in the grading table. In addition, all deaths related to an AE are to be classified as
grade 5.
PARAMETER GRADE 1 GRADE 2 GRADE 3 GRADE 4

MILD MODERATE SEVERE POTENTIALLY
LIFE-THREATENING
Clinical adverse Mild symptoms Moderate symptoms Severe symptoms Potentially life-threatening
event NOT causing no or causing greater than causing inability to symptoms causing inability to
identified minimal interference minimal interference perform usual social & perform basic self-care
elsewhere in the with usual social & with usual social & functional activities with functions with intervention
grading table functional activities functional activities intervention or indicated to prevent
with intervention not with intervention hospitalization indicated permanent impairment,
indicated indicated persistent disability, or death

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Major Clinical Conditions
Cardiovascular
LIFE-
THREATENING
Arrhythmia No symptoms AND No symptoms AND Non-life-threatening Life-threatening

(by ECG or physical No intervention Non-urgent symptoms AND arrhythmia OR Urgent
examination) indicated intervention indicated Non-urgent intervention indicated
Specify type, if applicable intervention indicated
Blood Pressure
Abnormalities 1
Hypertension (with the 140 to < 160 mmHg ≥ 160 to < 180 ≥ 180 mmHg systolic Life-threatening
lowest reading taken systolic mmHg systolic OR consequences in a
after repeat testing OR OR ≥ 110 mmHg diastolic participant not
during a visit) 90 to < 100 mmHg ≥ 100 to < 110 previously diagnosed
≥ 18 years of age diastolic mmHg diastolic with hypertension (e.g.,
malignant hypertension)
OR Hospitalization
indicated
< 18 years of age > 120/80 mmHg ≥ 95th to < 99th ≥ 99th percentile Life-threatening
percentile + 5 mmHg + 5 mmHg adjusted consequences in a
adjusted for age, for age, height, and participant not
height, and gender gender (systolic previously diagnosed
(systolic and/or and/or diastolic) with hypertension (e.g.,
diastolic) malignant hypertension)
OR Hospitalization
indicated
Hypotension No symptoms Symptoms corrected Symptoms AND IV Shock requiring use of
with oral fluid fluids indicated vasopressors or
replacement mechanical assistance to
maintain blood pressure
Cardiac Ischemia or NA NA New symptoms with Unstable angina OR

Infarction ischemia (stable Acute myocardial
Report only one angina) OR New infarction
testing consistent with
ischemia
Heart Failure No symptoms AND Symptoms with mild Symptoms at rest or Life-threatening
Laboratory or to moderate activity with minimal activity consequences OR Urgent
cardiac imaging or exertion or exertion (e.g., intervention indicated
abnormalities hypoxemia) OR (e.g., vasoactive
Intervention indicated medications, ventricular
(e.g., oxygen) assist device, heart
transplant)
Hemorrhage NA Symptoms AND No Symptoms AND Life-threatening

(with significant acute transfusion indicated Transfusion of ≤ 2 hypotension OR
blood loss) units packed RBCs Transfusion of > 2 units
indicated packed RBCs (for
children, packed RBCs
> 10 cc/kg) indicated
1
Blood pressure norms for children < 18 years of age can be found in: Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk
Reduction in Children and Adolescents. Pediatrics 2011;128;S213; originally published online November 14, 2011; DOI: 10.1542/peds.2009-
2107C.

Page 7
Cardiovascular
LIFE-
THREATENING
Prolonged PR Interval PR interval 0.21 to < PR interval ≥ 0.25 Type II 2nd degree AV Complete AV block
or AV Block 0.25 seconds seconds OR Type I block OR Ventricular
Report only one 2nd degree AV block pause ≥ 3.0 seconds
> 16 years of age
≤ 16 years of age 1st degree AV block Type I 2nd degree AV Type II 2nd degree AV Complete AV block
(PR interval block block OR Ventricular
> normal for age and pause ≥ 3.0 seconds
rate)
Prolonged QTc 0.45 to 0.47 seconds > 0.47 to 0.50 > 0.50 seconds OR Life-threatening
Interval 2 seconds ≥ 0.06 seconds above consequences (e.g.,
baseline Torsade de pointes, other
associated serious
ventricular dysrhythmia)
Thrombosis or NA Symptoms AND No Symptoms AND Life-threatening embolic

Embolism intervention indicated Intervention indicated event (e.g., pulmonary
Report only one embolism, thrombus)
2
As per Bazett’s formula.

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Dermatologic
LIFE-
THREATENING
Alopecia (scalp only) Detectable by study Obvious on visual NA NA

participant, inspection AND
caregiver, or Causing greater than
physician AND minimal interference
Causing no or with usual social &
minimal interference functional activities
with usual social &
functional activities
Bruising Localized to one Localized to more Generalized NA

area than one area
Cellulitis NA Non-parenteral IV treatment indicated Life-threatening

treatment indicated (e.g., IV antibiotics, consequences (e.g.,
(e.g., oral antibiotics, antifungals, antivirals) sepsis, tissue necrosis)
antifungals,
antivirals)
Hyperpigmentation Slight or localized Marked or NA NA

causing no or generalized causing
minimal interference greater than minimal
with usual social & interference with
functional activities usual social &
Hypopigmentation Slight or localized Marked or NA NA

causing no or generalized causing
minimal interference greater than minimal
with usual social & interference with
functional activities usual social &
Petechiae Localized to one Localized to more Generalized NA

area than one area
Pruritus 3 Itching causing no Itching causing Itching causing NA
(without skin lesions) or minimal greater than minimal inability to perform
interference with interference with usual social &
usual social & usual social & functional activities
functional activities functional activities
Rash Localized rash Diffuse rash OR Diffuse rash AND Extensive or generalized
Specify type, if applicable Target lesions Vesicles or limited bullous lesions OR
number of bullae or Ulceration of mucous
superficial ulcerations membrane involving two
of mucous membrane or more distinct mucosal
limited to one site sites OR Stevens-
Johnson syndrome OR
Toxic epidermal
necrolysis
3
For pruritus associated with injections or infusions, see the Site Reactions to Injections and Infusions section (page 23).

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Endocrine and Metabolic
LIFE-
THREATENING
Diabetes Mellitus Controlled without Controlled with Uncontrolled despite Life-threatening

medication medication OR treatment consequences (e.g.,
Modification of modification OR ketoacidosis,
current medication Hospitalization for hyperosmolar non-
regimen immediate glucose ketotic coma, end organ
control indicated failure)
Gynecomastia Detectable by study Obvious on visual Disfiguring changes NA
participant, inspection AND AND Symptoms
caregiver, or Causing pain with requiring intervention
physician AND greater than minimal or causing inability to
Causing no or interference with perform usual social
minimal interference usual social & & functional activities
with usual social & functional activities
Hyperthyroidism No symptoms AND Symptoms causing Symptoms causing Life-threatening

Abnormal laboratory greater than minimal inability to perform consequences (e.g.,
value interference with usual social & thyroid storm)
usual social & functional activities
functional activities OR Uncontrolled
OR Thyroid despite treatment
suppression therapy modification
indicated
Hypothyroidism No symptoms AND Symptoms causing Symptoms causing Life-threatening

Abnormal laboratory greater than minimal inability to perform consequences (e.g.,
value interference with usual social & myxedema coma)
functional activities OR Uncontrolled
OR Thyroid despite treatment
replacement therapy modification
indicated
Lipoatrophy 4 Detectable by study Obvious on visual Disfiguring changes NA

with usual social &
Lipohypertrophy 5 Detectable by study Obvious on visual Disfiguring changes NA

with usual social &
4
Definition: A disorder characterized by fat loss in the face, extremities, and buttocks.
5
Definition: A disorder characterized by abnormal fat accumulation on the back of the neck, breasts, and abdomen.

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Gastrointestinal
LIFE-
THREATENING
Anorexia Loss of appetite Loss of appetite Loss of appetite Life-threatening

without decreased associated with associated with consequences OR
oral intake decreased oral intake significant weight loss Aggressive intervention
without significant indicated (e.g., tube
weight loss feeding, total parenteral
nutrition)
Ascites No symptoms Symptoms AND Symptoms recur or Life-threatening
Intervention indicated persist despite consequences
(e.g., diuretics, intervention
therapeutic
paracentesis)
Bloating or Distension Symptoms causing Symptoms causing Symptoms causing NA

Report only one no or minimal greater than minimal inability to perform
Cholecystitis NA Symptoms AND Radiologic, Life-threatening

Medical intervention endoscopic, or consequences (e.g.,
indicated operative intervention sepsis, perforation)
indicated
Constipation NA Persistent Obstipation with Life-threatening
constipation requiring manual evacuation consequences (e.g.,
regular use of dietary indicated obstruction)
modifications,
laxatives, or enemas
Diarrhea
≥ 1 year of age Transient or Persistent episodes of Increase of ≥ 7 stools Life-threatening
intermittent episodes unformed to watery per 24-hour period consequences (e.g.,
of unformed stools stools OR Increase of OR IV fluid hypotensive shock)
OR Increase of ≤ 3 4 to 6 stools over replacement indicated
stools over baseline baseline per 24-hour
per 24-hour period period
< 1 year of age Liquid stools (more Liquid stools with Liquid stools with Life-threatening
unformed than increased number of moderate dehydration consequences (e.g.,
usual) but usual stools OR Mild liquid stools resulting in
number of stools dehydration severe dehydration,
hypotensive shock)
Dysphagia or Symptoms but able Symptoms causing Symptoms causing Life-threatening

Odynophagia to eat usual diet altered dietary intake severely altered reduction in oral intake
Report only one and with no intervention dietary intake with
specify location indicated intervention indicated
Gastrointestinal Not requiring Endoscopic Transfusion indicated Life-threatening

Bleeding intervention other intervention indicated consequences (e.g.,
than iron hypotensive shock)
supplement

Page 11
Gastrointestinal
LIFE-
THREATENING
Mucositis or Stomatitis Mucosal erythema Patchy Confluent Life-threatening

Report only one and pseudomembranes or pseudomembranes or consequences (e.g.,
specify location ulcerations ulcerations OR aspiration, choking) OR
Mucosal bleeding Tissue necrosis OR
with minor trauma Diffuse spontaneous
mucosal bleeding
Nausea Transient (< 24 Persistent nausea Persistent nausea Life-threatening

hours) or resulting in decreased resulting in minimal consequences (e.g.,
intermittent AND oral intake for 24 to oral intake for > 48 hypotensive shock)
No or minimal 48 hours hours OR
interference with Rehydration indicated
oral intake (e.g., IV fluids)
Pancreatitis NA Symptoms with Symptoms with Life-threatening

hospitalization not hospitalization consequences (e.g.,
indicated indicated circulatory failure,
hemorrhage, sepsis)
Perforation NA NA Intervention indicated Life-threatening

(colon or rectum) consequences
Proctitis Rectal discomfort Symptoms causing Symptoms causing Life-threatening

with no intervention greater than minimal inability to perform consequences (e.g.,
indicated interference with usual social & perforation)
functional activities OR Operative
OR Medical intervention indicated
intervention indicated
Rectal Discharge Visible discharge Discharge requiring NA NA

the use of pads
Vomiting Transient or Frequent episodes Persistent vomiting Life-threatening

intermittent AND with no or mild resulting in orthostatic consequences (e.g.,
No or minimal dehydration hypotension OR hypotensive shock)
interference with Aggressive
oral intake rehydration indicated
(e.g., IV fluids)

Page 12
Musculoskeletal
LIFE-
THREATENING
Arthralgia Joint pain causing Joint pain causing Joint pain causing Disabling joint pain
no or minimal greater than minimal inability to perform causing inability to
interference with interference with usual social & perform basic self-care
usual social & usual social & functional activities functions
Arthritis Stiffness or joint Stiffness or joint Stiffness or joint Disabling joint stiffness
swelling causing no swelling causing swelling causing or swelling causing
or minimal greater than minimal inability to perform inability to perform basic
interference with interference with usual social & self-care functions
Myalgia (generalized) Muscle pain causing Muscle pain causing Muscle pain causing Disabling muscle pain
Osteonecrosis NA No symptoms but Bone pain with Disabling bone pain with
with radiographic radiographic findings radiographic findings
findings AND No OR Operative causing inability to
operative intervention intervention indicated perform basic self-care
indicated functions
Osteopenia 6
≥ 30 years of age BMD t-score NA NA NA
-2.5 to -1
< 30 years of age BMD z-score NA NA NA
-2 to -1
Osteoporosis6
≥ 30 years of age NA BMD t-score < -2.5 Pathologic fracture Pathologic fracture
(e.g., compression causing life-threatening
fracture causing loss consequences
of vertebral height)
< 30 years of age NA BMD z-score < -2 Pathologic fracture Pathologic fracture
(e.g., compression causing life-threatening
fracture causing loss consequences
of vertebral height)
6
BMD t and z scores can be found in: Kanis JA on behalf of the World Health Organization Scientific Group (2007). Assessment of osteoporosis
at the primary health-care level. Technical Report. World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of
Sheffield, UK. 2007: Printed by the University of Sheffield.

Page 13
Neurologic
LIFE-
THREATENING
Acute CNS Ischemia NA NA Transient ischemic Cerebral vascular

attack accident (e.g., stroke
with neurological
deficit)
Altered Mental Status Changes causing no Mild lethargy or Confusion, memory Delirium OR
(for Dementia, see or minimal somnolence causing impairment, lethargy, Obtundation OR
Cognitive, Behavioral, or interference with greater than minimal or somnolence Coma
Attentional Disturbance usual social & interference with causing inability to
below) functional activities usual social & perform usual social
functional activities & functional activities
Ataxia Symptoms causing Symptoms causing Symptoms causing Disabling symptoms

OR No symptoms
with ataxia detected
on examination
Cognitive, Behavioral, Disability causing Disability causing Disability causing Disability causing
or Attentional no or minimal greater than minimal inability to perform inability to perform
Disturbance (includes interference with interference with usual social & basic self-care functions
dementia and attention usual social & usual social & functional activities OR Institutionalization
deficit disorder) functional activities functional activities OR Specialized indicated
Specify type, if applicable OR Specialized OR Specialized resources on a full-
resources not resources on part- time basis indicated
indicated time basis indicated
Developmental Delay Mild developmental Moderate Severe developmental Developmental

< 18 years of age delay, either motor developmental delay, delay, either motor or regression, either motor
or cognitive, as either motor or cognitive, as or cognitive, as
determined by cognitive, as determined by determined by
Specify type, if applicable comparison with a determined by comparison with a comparison with a
developmental comparison with a developmental developmental screening
screening tool developmental screening tool tool appropriate for the
appropriate for the screening tool appropriate for the setting
setting appropriate for the setting
setting
Headache Symptoms causing Symptoms causing Symptoms causing Symptoms causing

no or minimal greater than minimal inability to perform inability to perform
interference with interference with usual social & basic self-care functions
usual social & usual social & functional activities OR Hospitalization
functional activities functional activities indicated OR Headache
with significant
impairment of alertness
or other neurologic
function

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Neurologic
LIFE-
THREATENING
Neuromuscular Minimal muscle Muscle weakness Muscle weakness Disabling muscle

Weakness (includes weakness causing no causing greater than causing inability to weakness causing
myopathy and or minimal minimal interference perform usual social inability to perform
neuropathy) interference with with usual social & & functional activities basic self-care functions
Specify type, if applicable usual social & functional activities OR Respiratory muscle
functional activities weakness impairing
OR No symptoms ventilation
with decreased
strength on
examination
Neurosensory Alteration Minimal paresthesia Sensory alteration or Sensory alteration or Disabling sensory
(includes paresthesia and causing no or paresthesia causing paresthesia causing alteration or paresthesia
painful neuropathy) minimal greater than minimal inability to perform causing inability to
Specify type, if applicable interference with interference with usual social & perform basic self-care
OR No symptoms
with sensory
alteration on
examination
Seizures
New Onset Seizure NA NA 1 to 3 seizures Prolonged and repetitive
≥ 18 years of age seizures (e.g., status
epilepticus) OR Difficult
to control (e.g.,
refractory epilepsy)
< 18 years of age Seizure lasting < 5 Seizure lasting 5 to < Seizure lasting ≥ 20 Prolonged and repetitive
(includes new or pre- minutes with < 24 20 minutes with minutes OR > 24 seizures (e.g., status
existing febrile hours postictal state < 24 hours postictal hours postictal state epilepticus) OR Difficult
seizures) state to control (e.g.,
refractory epilepsy)
Pre-existing Seizure NA Increased frequency Change in seizure Prolonged and repetitive
from previous level character either in seizures (e.g., status
of control without duration or quality epilepticus) OR Difficult
change in seizure (e.g., severity or to control (e.g.,
character focality) refractory epilepsy)
Syncope Near syncope Loss of consciousness Loss of consciousness NA

without loss of with no intervention AND Hospitalization
consciousness (e.g., indicated or intervention
pre-syncope) required

Page 15
Pregnancy, Puerperium, and Perinatal
LIFE-
THREATENING
Fetal Death or Stillbirth NA NA Fetal loss occurring at NA

(report using mother’s ≥ 20 weeks gestation
participant ID)
Report only one
Preterm Delivery 7 Delivery at 34 to Delivery at 28 to Delivery at 24 to Delivery at < 24 weeks
(report using mother’s < 37 weeks < 34 weeks < 28 weeks gestational age
participant ID) gestational age gestational age gestational age
Spontaneous Abortion Chemical pregnancy Uncomplicated Complicated NA

or Miscarriage 8 (report spontaneous abortion spontaneous abortion
using mother’s participant or miscarriage or miscarriage
ID)
Report only one
7
Definition: A delivery of a live-born neonate occurring at ≥ 20 to < 37 weeks gestational age.
8
Definition: A clinically recognized pregnancy occurring at < 20 weeks gestational age.

Page 16
Psychiatric
LIFE-
THREATENING
Insomnia Mild difficulty Moderate difficulty Severe difficulty NA

falling asleep, falling asleep, staying falling asleep, staying
staying asleep, or asleep, or waking up asleep, or waking up
waking up early early early
Psychiatric Disorders Symptoms with Symptoms with Symptoms with Threatens harm to self or
(includes anxiety, intervention not intervention indicated hospitalization others OR Acute
depression, mania, and indicated OR OR Behavior causing indicated OR psychosis OR Behavior
psychosis) Behavior causing no greater than minimal Behavior causing causing inability to
Specify disorder or minimal interference with inability to perform perform basic self-care
interference with usual social & usual social & functions
usual social & functional activities functional activities
Suicidal Ideation or Preoccupied with Preoccupied with Thoughts of killing Suicide attempted
Attempt thoughts of death thoughts of death oneself with partial or
Report only one AND No wish to kill AND Wish to kill complete plans but no
oneself oneself with no attempt to do so OR
specific plan or intent Hospitalization
indicated

Page 17
Respiratory
LIFE-
THREATENING
Acute Bronchospasm Forced expiratory Forced expiratory Forced expiratory Forced expiratory
volume in 1 second volume in 1 second or volume in 1 second volume in 1 second or
or peak flow peak flow 50 to or peak flow 25 to peak flow < 25% OR
reduced to < 70% OR Symptoms < 50% OR Symptoms Life-threatening
≥ 70 to < 80% OR with intervention causing inability to respiratory or
Mild symptoms with indicated OR perform usual social hemodynamic
intervention not Symptoms causing & functional compromise OR
indicated greater than minimal activities Intubation
interference with
usual social &
Dyspnea or Respiratory Dyspnea on exertion Dyspnea on exertion Dyspnea at rest Respiratory failure with
Distress with no or minimal causing greater than causing inability to ventilator support
Report only one interference with minimal interference perform usual social indicated (e.g., CPAP,
usual social & with usual social & & functional BPAP, intubation)
functional activities functional activities activities OR Pulse
OR Wheezing OR OR Nasal flaring OR oximetry < 90%
Minimal increase in Intercostal retractions
respiratory rate for OR Pulse oximetry 90
age to < 95%

Page 18
Sensory
LIFE-
THREATENING
Hearing Loss
≥ 12 years of age NA Hearing aid or Hearing aid or Profound bilateral
intervention not intervention indicated hearing loss (> 80 dB at
indicated 2 kHz and above) OR
Non-serviceable hearing
(i.e., >50 dB audiogram
and <50% speech
discrimination)
< 12 years of age > 20 dB hearing loss > 20 dB hearing loss > 20 dB hearing loss Audiologic indication for
(based on a 1, 2, 3, 4, 6 at ≤ 4 kHz at > 4 kHz at ≥ 3 kHz in one ear cochlear implant and
and 8 kHz audiogram) with additional speech additional speech-
language related language related services
services indicated indicated (where
(where available) OR available)
Hearing loss
sufficient to indicate
therapeutic
intervention,
including hearing aids
Tinnitus Symptoms causing Symptoms causing Symptoms causing NA

no or minimal greater than minimal inability to perform
with intervention not with intervention
indicated indicated
Uveitis No symptoms AND Anterior uveitis with Posterior or pan- Disabling visual loss in
Detectable on symptoms OR uveitis OR Operative affected eye(s)
examination Medicamylasal intervention indicated
intervention indicated
Vertigo Vertigo causing no Vertigo causing Vertigo causing Disabling vertigo
or minimal greater than minimal inability to perform causing inability to
Visual Changes Visual changes Visual changes Visual changes Disabling visual loss in
(assessed from baseline) causing no or causing greater than causing inability to affected eye(s)
minimal interference minimal interference perform usual social
with usual social & with usual social & & functional activities

Page 19
Systemic
LIFE-
THREATENING
Acute Allergic Localized urticaria Localized urticaria Generalized urticaria Acute anaphylaxis OR
Reaction (wheals) with no with intervention OR Angioedema with Life-threatening
medical intervention indicated OR Mild intervention indicated bronchospasm OR
indicated angioedema with no OR Symptoms of mild Laryngeal edema
intervention bronchospasm
indicated
Chills Symptoms causing no Symptoms causing Symptoms causing NA
or minimal greater than inability to perform
interference with usual minimal usual social &
social & functional interference with functional activities
activities usual social &
Cytokine Release Mild signs and Therapy (i.e., Prolonged severe signs Life-threatening
Syndrome 9 symptoms AND antibody infusion) and symptoms OR consequences (e.g.,
Therapy (i.e., antibody interruption Recurrence of requiring pressor or
infusion) interruption indicated AND symptoms following ventilator support)
not indicated Responds promptly initial improvement
to symptomatic
treatment OR
Prophylactic
medications
indicated for ≤ 24
hours
Fatigue or Malaise Symptoms causing no Symptoms causing Symptoms causing Incapacitating symptoms
Report only one or minimal greater than inability to perform of fatigue or malaise
interference with usual minimal usual social & causing inability to
social & functional interference with functional activities perform basic self-care
activities usual social & functions
Fever (non-axillary 38.0 to < 38.6°C or ≥ 38.6 to < 39.3°C ≥ 39.3 to < 40.0°C or ≥ 40.0°C or ≥ 104.0°F
temperatures only) 100.4 to < 101.5°F or ≥ 101.5 to ≥ 102.7 to < 104.0°F
< 102.7°F
Pain 10 (not associated Pain causing no or Pain causing greater Pain causing inability Disabling pain causing
with study agent minimal interference than minimal to perform usual social inability to perform basic
injections and not with usual social & interference with & functional activities self-care functions OR
specified elsewhere) functional activities usual social & Hospitalization indicated
Specify location functional activities
Serum Sickness 11 Mild signs and Moderate signs and Severe signs and Life-threatening
symptoms symptoms AND symptoms AND consequences (e.g.,
Intervention Higher level requiring pressor or
indicated (e.g., intervention indicated ventilator support)
antihistamines) (e.g., steroids or IV
fluids)
9
Definition: A disorder characterized by nausea, headache, tachycardia, hypotension, rash, and/or shortness of breath.
10
For pain associated with injections or infusions, see the Site Reactions to Injections and Infusions section (page 23).
11
Definition: A disorder characterized by fever, arthralgia, myalgia, skin eruptions, lymphadenopathy, marked discomfort, and/or dyspnea.

Page 20
Systemic
LIFE-
THREATENING
Underweight 12
> 5 to 19 years of NA WHO BMI z-score WHO BMI z-score WHO BMI z-score
age < -2 to ≤ -3 < -3 < -3 with life-threatening
consequences
2 to 5 years of age NA WHO Weight-for- WHO Weight-for- WHO Weight-for-height
height z-score height z-score < -3 z-score < -3 with life-
< -2 to ≤ -3 threatening consequences
< 2 years of age NA WHO Weight-for- WHO Weight-for- WHO Weight-for-length

length z-score length z-score < -3 z-score < -3 with life-
< -2 to ≤ -3 threatening consequences
Weight Loss (excludes NA 5 to < 9% loss in ≥ 9 to < 20% loss in ≥ 20% loss in body weight
postpartum weight body weight from body weight from from baseline OR
loss) baseline baseline Aggressive intervention
indicated (e.g., tube
feeding, total parenteral
nutrition)
12
WHO reference tables may be accesed by clicking the desired age range or by accessing the following URLs:
http://www.who.int/growthref/who2007_bmi_for_age/en/ for participants > 5 to 19 years of age and
http://www.who.int/childgrowth/standards/chart_catalogue/en/ for those ≤ 5 years of age.

Page 21
Urinary
LIFE-
THREATENING
Urinary Tract NA Signs or symptoms of Signs or symptoms of Obstruction causing life-

Obstruction urinary tract urinary tract threatening
obstruction without obstruction with consequences
hydronephrosis or hydronephrosis or
renal dysfunction renal dysfunction

Page 22
Site Reactions to Injections and Infusions
LIFE-
THREATENING
Injection Site Pain or Pain or tenderness Pain or tenderness Pain or tenderness Pain or tenderness
Tenderness causing no or causing greater than causing inability to causing inability to
Report only one minimal limitation minimal limitation of perform usual social perform basic self-care
of use of limb use of limb & functional activities function OR
Hospitalization indicated
Injection Site Erythema

or Redness 13
Report only one
2.5 to < 5 cm in ≥ 5 to < 10 cm in ≥ 10 cm in diameter Potentially life-
> 15 years of age diameter OR 6.25 to diameter OR ≥ 25 to OR ≥ 100 cm2 surface threatening
< 25 cm2 surface < 100 cm2 surface area OR Ulceration consequences (e.g.,
area AND area OR Symptoms OR Secondary abscess, exfoliative
Symptoms causing causing greater than infection OR Phlebitis dermatitis, necrosis
no or minimal minimal interference OR Sterile abscess involving dermis or
interference with with usual social & OR Drainage OR deeper tissue)
usual social & functional activities Symptoms causing
functional activities inability to perform
usual social &
≤ 15 years of age ≤ 2.5 cm in diameter > 2.5 cm in diameter ≥ 50% surface area of Potentially life-
with < 50% surface the extremity segment threatening
area of the extremity involved (e.g., upper consequences (e.g.,
segment involved arm or thigh) OR abscess, exfoliative
(e.g., upper arm or Ulceration OR dermatitis, necrosis
thigh) Secondary infection involving dermis or
OR Phlebitis OR deeper tissue)
Sterile abscess OR
Drainage
Injection Site Same as for Same as for Injection Same as for Injection Same as for Injection
Induration or Swelling Injection Site Site Erythema or Site Erythema or Site Erythema or
Report only one Erythema or Redness, > 15 years Redness, > 15 years Redness, > 15 years of
Redness, > 15 years of age of age age
> 15 years of age of age
≤ 15 years of age Same as for Same as for Injection Same as for Injection Same as for Injection
Injection Site Site Erythema or Site Erythema or Site Erythema or
Erythema or Redness, ≤ 15 years Redness, ≤ 15 years Redness, ≤ 15 years of
Redness, ≤ 15 years of age of age age
of age
Injection Site Pruritus Itching localized to Itching beyond the Generalized itching NA
the injection site that injection site that is causing inability to
is relieved not generalized OR perform usual social
spontaneously or in Itching localized to & functional activities
< 48 hours of the injection site
treatment requiring ≥ 48 hours
treatment
13
Injection Site Erythema or Redness should be evaluated and graded using the greatest single diameter or measured surface area.

Page 23
Laboratory Values
Chemistries
LIFE-
THREATENING
Acidosis NA pH ≥ 7.3 to < LLN pH < 7.3 without life- pH < 7.3 with life-
threatening threatening
consequences consequences
Albumin, Low 3.0 to < LLN ≥ 2.0 to < 3.0 < 2.0 NA
(g/dL; g/L) 30 to < LLN ≥ 20 to < 30 < 20
Alkaline Phosphatase, 1.25 to < 2.5 2.5 to < 5.0 x ULN 5.0 to < 10.0 x ULN ≥ 10.0 x ULN
High x ULN
Alkalosis NA pH > ULN to ≤ 7.5 pH > 7.5 without life- pH > 7.5 with life-
threatening threatening
ALT or SGPT, High 1.25 to < 2.5 2.5 to < 5.0 x ULN 5.0 to < 10.0 x ULN ≥ 10.0 x ULN
Report only one x ULN
Amylase (Pancreatic) or 1.1 to < 1.5 x ULN 1.5 to < 3.0 x ULN 3.0 to < 5.0 x ULN ≥ 5.0 x ULN
Amylase (Total), High
Report only one
AST or SGOT, High 1.25 to < 2.5 2.5 to < 5.0 x ULN 5.0 to < 10.0 x ULN ≥ 10.0 x ULN
Report only one x ULN
Bicarbonate, Low 16.0 to < LLN 11.0 to < 16.0 8.0 to < 11.0 < 8.0
(mEq/L; mmol/L) 16.0 to < LLN 11.0 to < 16.0 8.0 to < 11.0 < 8.0
Bilirubin
Direct Bilirubin 14,
High NA NA > ULN > ULN with life-
> 28 days of age threatening
consequences (e.g., signs
and symptoms of liver
failure)
≤ 28 days of age ULN to ≤ 1 mg/dL > 1 to ≤ 1.5 mg/dL > 1.5 to ≤ 2 mg/dL > 2 mg/dL
Total Bilirubin, High
> 28 days of age 1.1 to < 1.6 x ULN 1.6 to < 2.6 x ULN 2.6 to < 5.0 x ULN ≥ 5.0 x ULN
≤ 28 days of age See Appendix A. See Appendix A. See Appendix A. See Appendix A. Total
Total Bilirubin for Total Bilirubin for Total Bilirubin for Bilirubin for Term and
Term and Preterm Term and Preterm Term and Preterm Preterm Neonates
Neonates Neonates Neonates
Calcium, High
(mg/dL; mmol/L)
10.6 to < 11.5 11.5 to < 12.5 12.5 to < 13.5 ≥ 13.5
≥ 7 days of age
2.65 to < 2.88 2.88 to < 3.13 3.13 to < 3.38 ≥ 3.38
< 7 days of age 11.5 to < 12.4 12.4 to < 12.9 12.9 to < 13.5 ≥ 13.5
2.88 to < 3.10 3.10 to < 3.23 3.23 to < 3.38 ≥ 3.38
14
Direct bilirubin > 1.5 mg/dL in a participant < 28 days of age should be graded as grade 2, if < 10% of the total bilirubin.

Page 24
Chemistries
LIFE-
THREATENING
Calcium (Ionized), High > ULN to < 6.0 6.0 to < 6.4 6.4 to < 7.2 ≥ 7.2
(mg/dL; mmol/L) > ULN to < 1.5 1.5 to < 1.6 1.6 to < 1.8 ≥ 1.8
Calcium, Low
(mg/dL; mmol/L)
7.8 to < 8.4 7.0 to < 7.8 6.1 to < 7.0 < 6.1
≥ 7 days of age
1.95 to < 2.10 1.75 to < 1.95 1.53 to < 1.75 < 1.53
< 7 days of age 6.5 to < 7.5 6.0 to < 6.5 5.50 to < 6.0 < 5.50
1.63 to < 1.88 1.50 to < 1.63 1.38 to < 1.50 < 1.38
Calcium (Ionized), Low < LLN to 4.0 3.6 to < 4.0 3.2 to < 3.6 < 3.2
(mg/dL; mmol/L) < LLN to 1.0 0.9 to < 1.0 0.8 to < 0.9 < 0.8
Cardiac Troponin I, NA NA NA Levels consistent with

High myocardial infarction or
unstable angina as
defined by the local
laboratory
Creatine Kinase, High 3 to < 6 x ULN 6 to < 10 x ULN 10 to < 20 x ULN ≥ 20 x ULN
Creatinine, High 1.1 to 1.3 x ULN > 1.3 to 1.8 x ULN > 1.8 to < 3.5 ≥ 3.5 x ULN OR
OR Increase of x ULN OR Increase Increase of ≥ 2.0 x
> 0.3 mg/dL above of 1.5 to < 2.0 x above baseline
baseline above baseline
Creatinine Clearance 15 NA < 90 to 60 ml/min or < 60 to 30 ml/min or < 30 ml/min or

or eGFR, Low ml/min/1.73 m2 ml/min/1.73 m2 ml/min/1.73 m2
Report only one OR OR OR
10 to < 30% decrease ≥ 30 to < 50% ≥ 50% decrease from
from baseline decrease from baseline or dialysis
baseline needed
Glucose
(mg/dL; mmol/L)
110 to 125 > 125 to 250 > 250 to 500 > 500
Fasting, High 6.11 to < 6.95 6.95 to < 13.89 13.89 to < 27.75 ≥ 27.75
Nonfasting, High 116 to 160 > 160 to 250 > 250 to 500 > 500
6.44 to < 8.89 8.89 to < 13.89 13.89 to < 27.75 ≥ 27.75
Glucose, Low
(mg/dL; mmol/L)
55 to 64 40 to < 55 30 to < 40 < 30
≥ 1 month of age
3.05 to 3.55 2.22 to < 3.05 1.67 to < 2.22 < 1.67
< 1 month of age 50 to 54 40 to < 50 30 to < 40 < 30
2.78 to 3.00 2.22 to < 2.78 1.67 to < 2.22 < 1.67
Lactate, High ULN to < 2.0 ≥ 2.0 x ULN without Increased lactate with Increased lactate with
x ULN without acidosis pH < 7.3 without life- pH < 7.3 with life-
acidosis threatening threatening
15
Use the applicable formula (i.e., Cockroft-Gault in mL/min or Schwatrz in mL/min/1.73m2).

Page 25
Chemistries
LIFE-
THREATENING
Lipase, High 1.1 to < 1.5 x ULN 1.5 to < 3.0 x ULN 3.0 to < 5.0 x ULN ≥ 5.0 x ULN
Lipid Disorders
(mg/dL; mmol/L)
Cholesterol, Fasting,
High
200 to < 240 240 to < 300 ≥ 300 NA
≥ 18 years of age 5.18 to < 6.19 6.19 to < 7.77 ≥ 7.77
< 18 years of age 170 to < 200 200 to < 300 ≥ 300 NA
4.40 to < 5.15 5.15 to < 7.77 ≥ 7.77
LDL, Fasting, High
≥ 18 years of age 130 to < 160 160 to < 190 ≥ 190 NA
3.37 to < 4.12 4.12 to < 4.90 ≥ 4.90
> 2 to < 18 years of 110 to < 130 130 to < 190 ≥ 190 NA
age 2.85 to < 3.34 3.34 to < 4.90 ≥ 4.90
Triglycerides, Fasting, 150 to 300 >300 to 500 >500 to < 1,000 > 1,000
High 1.71 to 3.42 >3.42 to 5.7 >5.7 to 11.4 > 11.4
Magnesium 16, Low 1.2 to < 1.4 0.9 to < 1.2 0.6 to < 0.9 < 0.6
(mEq/L; mmol/L) 0.60 to < 0.70 0.45 to < 0.60 0.30 to < 0.45 < 0.30
Phosphate, Low
(mg/dL; mmol/L)
2.0 to < LLN 1.4 to < 2.0 1.0 to < 1.4 < 1.0
> 14 years of age
0.81 to < LLN 0.65 to < 0.81 0.32 to < 0.65 < 0.32
1 to 14 years of age 3.0 to < 3.5 2.5 to < 3.0 1.5 to < 2.5 < 1.5
0.97 to < 1.13 0.81 to < 0.97 0.48 to < 0.81 < 0.48
< 1 year of age 3.5 to < 4.5 2.5 to < 3.5 1.5 to < 2.5 < 1.5
1.13 to < 1.45 0.81 to < 1.13 0.48 to < 0.81 < 0.48
Potassium, High 5.6 to < 6.0 6.0 to < 6.5 6.5 to < 7.0 ≥ 7.0
(mEq/L; mmol/L) 5.6 to < 6.0 6.0 to < 6.5 6.5 to < 7.0 ≥ 7.0
Potassium, Low 3.0 to < 3.4 2.5 to < 3.0 2.0 to < 2.5 < 2.0
(mEq/L; mmol/L) 3.0 to < 3.4 2.5 to < 3.0 2.0 to < 2.5 < 2.0
Sodium, High 146 to < 150 150 to < 154 154 to < 160 ≥ 160
(mEq/L; mmol/L) 146 to < 150 150 to < 154 154 to < 160 ≥ 160
Sodium, Low 130 to < 135 125 to < 130 121 to < 125 ≤ 120
(mEq/L; mmol/L) 130 to < 135 125 to < 135 121 to < 125 ≤ 120
Uric Acid, High 7.5 to < 10.0 10.0 to < 12.0 12.0 to < 15.0 ≥ 15.0
(mg/dL; mmol/L) 0.45 to < 0.59 0.59 to < 0.71 0.71 to < 0.89 ≥ 0.89
16
To convert a magnesium value from mg/dL to mmol/L, laboratories should multiply by 0.4114.

Page 26
Hematology
LIFE-
THREATENING
Absolute CD4+ Count,

Low
(cell/mm3; cells/L)
> 5 years of age 300 to < 400 200 to < 300 100 to < 200 < 100
(not HIV infected) 300 to < 400 200 to < 300 100 to < 200 < 100
Absolute Lymphocyte
Count, Low
(cell/mm3; cells/L)
600 to < 650 500 to < 600 350 to < 500 < 350
> 5 years of age 0.600 x 109 to 0.500 x 109 to 0.350 x 109 to < 0.350 x 109
(not HIV infected) < 0.650 x 109 < 0.600 x 109 < 0.500 x 109
Absolute Neutrophil
Count (ANC), Low
(cells/mm3; cells/L)
800 to 1,000 600 to 799 400 to 599 < 400
> 7 days of age
0.800 x 109 to 1.000 0.600 x 109 to 0.799 x 0.400 x 109 to 0.599 x < 0.400 x 109
x 109 109 109
2 to 7 days of age 1,250 to 1,500 1,000 to 1,249 750 to 999 < 750
1.250 x 109 to 1.500 1.000 x 109 to 1.249 x 0.750 x 109 to 0.999 x < 0.750 x 109
x 109 109 109
≤ 1 day of age 4,000 to 5,000 3,000 to 3,999 1,500 to 2,999 < 1,500
9
4.000 x 10 to 3.000 x 109 to 3.999 x 1.500 x 109 to 2.999 x < 1.500 x 109
5.000 x 109 109 109
Fibrinogen, Decreased 100 to < 200 75 to < 100 50 to < 75 < 50

(mg/dL; g/L) 1.00 to < 2.00 0.75 to < 1.00 0.50 to < 0.75 < 0.50
OR OR OR OR
0.75 to < 1.00 ≥ 0.50 to < 0.75 0.25 to < 0.50 < 0.25 x LLN
x LLN x LLN x LLN OR Associated with
gross bleeding
Hemoglobin 17, Low

(g/dL; mmol/L) 18
≥ 13 years of age 10.0 to 10.9 9.0 to < 10.0 7.0 to < 9.0 < 7.0
(male only) 6.19 to 6.76 5.57 to < 6.19 4.34 to < 5.57 < 4.34
≥ 13 years of age 9.5 to 10.4 8.5 to < 9.5 6.5 to < 8.5 < 6.5
(female only) 5.88 to 6.48 5.25 to < 5.88 4.03 to < 5.25 < 4.03
17
Male and female sex are defined as sex at birth.
18
The conversion factor used to convert g/dL to mmol/L is 0.6206 and is the most commonly used conversion factor. For grading hemoglobin
results obtained by an analytic method with a conversion factor other than 0.6206, the result must be converted to g/dL using the appropriate
conversion factor for the particular laboratory.

Page 27
Hematology
LIFE-
THREATENING
57 days of age to < 13 9.5 to 10.4 8.5 to < 9.5 6.5 to < 8.5 < 6.5
years of age 5.88 to 6.48 5.25 to < 5.88 4.03 to < 5.25 < 4.03
(male and female)
36 to 56 days of age 8.5 to 9.6 7.0 to < 8.5 6.0 to < 7.0 < 6.0
(male and female) 5.26 to 5.99 4.32 to < 5.26 < 3.72
3.72 to < 4.32
22 to 35 days of age 9.5 to 11.0 8.0 to < 9.5 6.7 to < 8.0 < 6.7
(male and female) 5.88 to 6.86 4.94 to < 5.88 4.15 to < 4.94 < 4.15
8 to ≤ 21 days of age 11.0 to 13.0 9.0 to < 11.0 8.0 to < 9.0 < 8.0
≤ 7 days of age 13.0 to 14.0 10.0 to < 13.0 9.0 to < 10.0 < 9.0
INR, High 1.1 to < 1.5 x ULN 1.5 to < 2.0 x ULN 2.0 to < 3.0 x ULN ≥ 3.0 x ULN
(not on anticoagulation
therapy)
Methemoglobin 5.0 to < 10.0% 10.0 to < 15.0% 15.0 to < 20.0% ≥ 20.0%
(% hemoglobin)
PTT, High 1.1 to < 1.66 1.66 to < 2.33 2.33 to < 3.00 ≥ 3.00 x ULN
(not on anticoagulation x ULN x ULN x ULN
therapy)
Platelets, Decreased 100,000 to 50,000 to 25,000 to < 25,000
(cells/mm3; cells/L) < 124,999 < 100,000 < 50,000 < 25.000 x 109
100.000 x 109 to 50.000 x 109 to 25.000 x 109 to
< 124.999 x 109 < 100.000 x 109 < 50.000 x 109
PT, High 1.1 to < 1.25 1.25 to < 1.50 1.50 to < 3.00 ≥ 3.00 x ULN
(not on anticoagulation x ULN x ULN x ULN
therapy
WBC, Decreased
(cells/mm3; cells/L)
> 7 days of age 2,000 to 2,499 1,500 to 1,999 1,000 to 1,499 < 1,000
2.000 x 109 to 2.499 1.500 x 109 to 1.999 x 1.000 x 109 to 1.499 x < 1.000 x 109
x 109 109 109
≤ 7 days of age 5,500 to 6,999 4,000 to 5,499 2,500 to 3,999 < 2,500
5.500 x 109 to 6.999 4.000 x 109 to 5.499 x 2.500 x 109 to 3.999 x < 2.500 x 109
x 109 109 109

Page 28
Urinalysis
LIFE-
THREATENING
Glycosuria (random Trace to 1+ or 2+ or ˃ 250 to > 2+ or > 500 mg NA

collection tested by ≤ 250 mg ≤ 500 mg
dipstick)
Hematuria (not to be 6 to < 10 RBCs per ≥ 10 RBCs per high Gross, with or Life-threatening
reported based on dipstick high power field power field without clots OR consequences
findings or on blood With RBC casts OR
believed to be of Intervention indicated
menstrual origin)
Proteinuria (random 1+ 2+ 3+ or higher NA
collection tested by
dipstick)

Page 29
Appendix A.
Total Bilirubin Table for Term and Preterm Neonates
LIFE-
THREATENING
Total Bilirubin 19, High

(mg/dL; µmol/L) 20
Term Neonate 21 4 to < 7 7 to < 10 10 to < 17 ≥ 17

< 24 hours of age 68.4 to < 119.7 119.7 to < 171 171 to < 290.7 ≥ 290.7
24 to < 48 hours of 5 to < 8 8 to < 12 12 to < 19 ≥ 19

age 85.5 to < 136.8 136.8 to < 205.2 205.2 to < 324.9 ≥ 324.9
48 to < 72 hours of 8.5 to < 13 13 to < 15 15 to < 22 ≥ 22
age 145.35 to < 222.3 222.3 to < 256.5 256.5 to < 376.2 ≥ 376.2
72 hours to < 7 days 11 to < 16 16 to < 18 18 to < 24 ≥ 24
of age 188.1 to < 273.6 273.6 to < 307.8 307.8 to < 410.4 ≥ 410.4
7 to 28 days of age 5 to < 10 10 to < 20 20 to < 25 ≥ 25
(breast feeding) 85.5 to < 171 171 to < 342 342 to < 427.5 ≥ 427.5
7 to 28 days of age 1.1 to < 1.6 x ULN 1.6 to < 2.6 x ULN 2.6 to < 5.0 x ULN ≥ 5.0 x ULN
(not breast feeding)
Preterm Neonate20 Same as for Total Same as for Total Same as for Total Same as for Total
35 to < 37 weeks Bilirubin, High, Term Bilirubin, High, Term Bilirubin, High, Bilirubin, High, Term
gestational age Neonate (based on Neonate (based on Term Neonate (based Neonate (based on
days of age). days of age). on days of age). days of age).
32 to < 35 weeks NA NA 10 to < 14 ≥ 14
gestational age and 171 to < 239.4 ≥ 239.4
< 7 days of age
28 to < 32 weeks NA NA 6 to < 10 ≥ 10
gestational age and 102.6 to < 171 ≥ 171
< 7 days of age
< 28 weeks NA NA 5 to < 8 ≥8
gestational age and 85.5 to < 136.8 ≥ 136.8
< 7 days of age
7 to 28 days of age 5 to < 10 10 to < 20 20 to < 25 ≥ 25
(breast feeding) 85.5 to < 171 171 to < 342 342 to < 427.5 ≥ 427.5
7 to 28 days of age 1.1 to < 1.6 x ULN 1.6 to < 2.6 x ULN 2.6 to < 5.0 x ULN ≥ 5.0 x ULN
(not breast feeding)
19
Severity grading for total bilirubin in neonates is complex because of rapidly changing total bilirubin normal ranges in the first week of life
followed by the benign phenomenon of breast milk jaundice after the first week of life. Severity grading in this appendix corresponds
approximately to cut-offs for indications for phototherapy at grade 3 and for exchange transfusion at grade 4.
20
A laboratory value of 1 mg/dL is equivalent to 17.1 µmol/L.
21
Definitions: Term is defined as ≥ 37 weeks gestational age; near-term, as ≥ 35 weeks gestational age; preterm, as < 35 weeks gestational age;
and neonate, as 0 to 28 days of age.

Page 30

Daids Ae Grading Table v2 Nov2014

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Division of AIDS (DAIDS) Table for

Grading the Severity of Adult and

DAIDS AE Grading Table Version 2.0- November 2014

DAIDS AE Grading Table Version 2.0- November 2014

DAIDS AE Grading Table Version 2.0- November 2014

Other points to consider include:

Selecting and Reporting a Primary AE Term

DAIDS AE Grading Table Version 2.0- November 2014

Grading Adult and Pediatric AEs

Reporting Pregnancy Outcomes

Determining Severity Grade for Parameters between Grades

DAIDS AE Grading Table Version 2.0- November 2014

Using Addenda 1-3: Grading Tables Used in Microbicide Studies

PARAMETER GRADE 1 GRADE 2 GRADE 3 GRADE 4

DAIDS AE Grading Table Version 2.0- November 2014

Arrhythmia No symptoms AND No symptoms AND Non-life-threatening Life-threatening

Cardiac Ischemia or NA NA New symptoms with Unstable angina OR

Hemorrhage NA Symptoms AND No Symptoms AND Life-threatening

DAIDS AE Grading Table Version 2.0- November 2014

Thrombosis or NA Symptoms AND No Symptoms AND Life-threatening embolic

DAIDS AE Grading Table Version 2.0- November 2014

Alopecia (scalp only) Detectable by study Obvious on visual NA NA

Bruising Localized to one Localized to more Generalized NA

Cellulitis NA Non-parenteral IV treatment indicated Life-threatening

Hyperpigmentation Slight or localized Marked or NA NA

Hypopigmentation Slight or localized Marked or NA NA

Petechiae Localized to one Localized to more Generalized NA

DAIDS AE Grading Table Version 2.0- November 2014

Diabetes Mellitus Controlled without Controlled with Uncontrolled despite Life-threatening

Hyperthyroidism No symptoms AND Symptoms causing Symptoms causing Life-threatening

Hypothyroidism No symptoms AND Symptoms causing Symptoms causing Life-threatening

Lipoatrophy 4 Detectable by study Obvious on visual Disfiguring changes NA

Lipohypertrophy 5 Detectable by study Obvious on visual Disfiguring changes NA

DAIDS AE Grading Table Version 2.0- November 2014

Anorexia Loss of appetite Loss of appetite Loss of appetite Life-threatening

Bloating or Distension Symptoms causing Symptoms causing Symptoms causing NA

Cholecystitis NA Symptoms AND Radiologic, Life-threatening

Dysphagia or Symptoms but able Symptoms causing Symptoms causing Life-threatening

Gastrointestinal Not requiring Endoscopic Transfusion indicated Life-threatening

DAIDS AE Grading Table Version 2.0- November 2014

Mucositis or Stomatitis Mucosal erythema Patchy Confluent Life-threatening

Nausea Transient (< 24 Persistent nausea Persistent nausea Life-threatening

Pancreatitis NA Symptoms with Symptoms with Life-threatening

Perforation NA NA Intervention indicated Life-threatening

Proctitis Rectal discomfort Symptoms causing Symptoms causing Life-threatening

Rectal Discharge Visible discharge Discharge requiring NA NA

Vomiting Transient or Frequent episodes Persistent vomiting Life-threatening

DAIDS AE Grading Table Version 2.0- November 2014

DAIDS AE Grading Table Version 2.0- November 2014

Acute CNS Ischemia NA NA Transient ischemic Cerebral vascular

Ataxia Symptoms causing Symptoms causing Symptoms causing Disabling symptoms

Developmental Delay Mild developmental Moderate Severe developmental Developmental

Headache Symptoms causing Symptoms causing Symptoms causing Symptoms causing

DAIDS AE Grading Table Version 2.0- November 2014

Neuromuscular Minimal muscle Muscle weakness Muscle weakness Disabling muscle

Syncope Near syncope Loss of consciousness Loss of consciousness NA

DAIDS AE Grading Table Version 2.0- November 2014

Fetal Death or Stillbirth NA NA Fetal loss occurring at NA

Spontaneous Abortion Chemical pregnancy Uncomplicated Complicated NA