Note:  The following toxicity table is a DRAFT and designed to provide
general guidance on parameters for monitoring safety in clinical
trials.  This toxicity table is not comprehensive and should not be
applied directly to all trials.  

 

When selecting a toxicity table, the following are some of the items
that must be taken into consideration:

 

-   The population being studied

    -   Does the clinical trial evaluate healthy subjects, subjects with
        a particular disease or condition? 

-   The stage of test article development

    -   Is the clinical trial a Phase I, II, III or IV?

-   The type of test article 

    -   Does the clinical trial evaluate a drug, device, vaccine
        or other biologic agent? 

-   The prior human and preclinical experience with the test article

    -   Are there any specific findings that require adjustment of the
        toxicity table? 

 

Single site clinical trials evaluating healthy subjects should conform
to the laboratory normal values at the single site. Multi-center
clinical trials should reconcile among their laboratory normal values
when evaluating a healthy volunteer population.

 

Please confer with the DMID protocol team and DMID\'s Office of Clinical
Research Affairs when selecting or developing a toxicity table for a
DMID-sponsored trial.

**[ABBREVIATIONS]{.underline}:** Abbreviations utilized in the Table:

> ULN = Upper Limit of Normal LLN = Lower Limit of Normal
>
> R~x~ = Therapy Req = Required
>
> Mod = Moderate IV = Intravenous
>
> ADL = Activities of Daily Living Dec = Decreased

**[ESTIMATING SEVERITY GRADE]{.underline}**

For abnormalities NOT found elsewhere in the Toxicity Tables use the
scale below to estimate grade of severity:

**GRADE 1 Mild** Transient or mild discomfort

(\< 48 hours); no medical intervention/therapy required

**GRADE 2 Moderate** Mild to moderate limitation in activity - some
assistance may be needed; no or minimal medical intervention/therapy
required

**GRADE 3 Severe** Marked limitation in activity, some assistance
usually required; medical intervention/therapy required,
hospitalizations possible

**GRADE 4 Life-threatening** Extreme limitation in activity, significant
assistance required; significant medical intervention/therapy required,
hospitalization or hospice care probable

**[SERIOUS OR LIFE-THREATENING AEs]{.underline}**

ANY clinical event deemed by the clinician to be serious or
life-threatening should be considered a grade 4 event. Clinical events
considered to be serious or life-threatening include, but are not
limited to: seizures, coma, tetany, diabetic ketoacidosis, disseminated
intravascular coagulation, diffuse petechiae, paralysis, acute
psychosis, severe depression.

# COMMENTS REGARDING THE USE OF THESE TABLES

**•** Standardized and commonly used toxicity tables (Division of AIDS,
NCI's Common Toxicity Criteria (CTC), and World Health Organization
(WHO)) have been adapted for use by the Division of Microbiology and
Infectious Diseases (DMID) and modified to better meet the needs of
participants in DMID trials.

**•** For parameters not included in the following Toxicity Tables,
sites should refer to the "Guide For Estimating Severity Grade" located
above.

• Criteria are generally grouped by body system.

• Some protocols may have additional protocol specific grading criteria,
which will supercede the use of these tables for specified criteria.

+-------------------+------------+----------+------------+-----------+
| ### HEMATOLOGY    |            |          |            |           |
+-------------------+------------+----------+------------+-----------+
| ###               | Grade 1    | Grade 2  | Grade 3    | Grade 4   |
+-------------------+------------+----------+------------+-----------+
| Hemoglobin        | 9.5 - 10.5 | 8.0 -    | 6.5 - 7.9  | \< 6.5    |
|                   | gm/dL      | 9.4gm/dL | gm/dL      | gm/dL     |
+-------------------+------------+----------+------------+-----------+
| Absolute          | 1000-      | 750-9    | 500        | \<        |
| Neutrophil Count  | 1500/mm^3^ | 99/mm^3^ | -749/mm^3^ | 500/mm^3^ |
+-------------------+------------+----------+------------+-----------+
| Platelets         | 75,000-99  | 50,      | 20,000-49  | \<20,     |
|                   | ,999/mm^3^ | 000-74,9 | ,999/mm^3^ | 000/mm^3^ |
|                   |            | 99/mm^3^ |            |           |
+-------------------+------------+----------+------------+-----------+
| WBCs              | 11,0       | 13,000-  | 15,000-    | \>30,000  |
|                   | 00-13,000/ |          |            | or        |
|                   | mm^3^      | 15,000   | 30         | \<1,000   |
|                   |            | /mm^3^   | ,000/mm^3^ | /mm^3^    |
+-------------------+------------+----------+------------+-----------+
| \%                | \> 80%     | 90 --    | \>95%      | \         |
| Polymorphonuclear |            | 95%      |            | -\-\-\-\- |
| Leucocytes + Band |            |          |            | \-\-\-\-- |
| Cells             |            |          |            |           |
+-------------------+------------+----------+------------+-----------+
| Abnormal          | Low:       | Low:     | Low:       | F         |
|                   |            |          |            | ibrinogen |
| Fibrinogen        | 100-200    | \<100    | \< 50      | a         |
|                   | mg/dL      | mg/dL    | mg/dL      | ssociated |
|                   |            |          |            | with      |
|                   | High:      | High:    | \-\-\-\-\  | gross     |
|                   |            |          | -\-\-\-\-- | bleeding  |
|                   | 400-600    | \>600    |            | or with   |
|                   | mg/dL      | mg/dL    |            | dis       |
|                   |            |          |            | seminated |
|                   |            |          |            | co        |
|                   |            |          |            | agulation |
+-------------------+------------+----------+------------+-----------+
| Fibrin Split      | 20-40      | 41-50    | 51-60      | \> 60     |
| Product           | mcg/ml     | mcg/ml   | mcg/ml     | mcg/ml    |
+-------------------+------------+----------+------------+-----------+
| Prothrombin       | 1.01 -     | 1.26-1.5 | 1.51 -3.0  | \>3 x ULN |
|                   | 1.25 x ULN | x ULN    | x ULN      |           |
| Time (PT)         |            |          |            |           |
+-------------------+------------+----------+------------+-----------+
| Activated Partial | 1.01 -1.66 | 1.67 -   | 2.34 - 3 x | \> 3 x    |
| Thromboplastin    | x ULN      | 2.33 x   | ULN        | ULN       |
| (APPT)            |            | ULN      |            |           |
+-------------------+------------+----------+------------+-----------+
| Methemoglobin     | 5.0 - 9.9  | 10.0 -   | 15.0 -     | \> 20.0 % |
|                   | %          | 14.9 %   | 19.9%      |           |
+-------------------+------------+----------+------------+-----------+

+-------------------+------------+----------+------------+-----------+
| **CHEMISTRIES**   |            |          |            |           |
+-------------------+------------+----------+------------+-----------+
|                   | Grade 1    | Grade 2  | Grade 3    | Grade 4   |
+-------------------+------------+----------+------------+-----------+
| Hyponatremia      | 130-135    | 123-129  | 116-122    | \< 116    |
|                   | mEq/L      | mEq/L    | mEq/L      | mEq/L or  |
|                   |            |          |            | abnormal  |
|                   |            |          |            | sodium    |
|                   |            |          |            | *with*    |
|                   |            |          |            | mental    |
|                   |            |          |            | status    |
|                   |            |          |            | changes   |
|                   |            |          |            | or        |
|                   |            |          |            | seizures  |
+-------------------+------------+----------+------------+-----------+
| Hypernatremia     | 146-150    | 151-157  | 158-165    | \> 165    |
|                   | mEq/L      | mEq/L    | mEq/L      | mEq/L or  |
|                   |            |          |            | abnormal  |
|                   |            |          |            | sodium    |
|                   |            |          |            | *with*    |
|                   |            |          |            | mental    |
|                   |            |          |            | status    |
|                   |            |          |            | changes   |
|                   |            |          |            | or        |
|                   |            |          |            | seizures  |
+-------------------+------------+----------+------------+-----------+
| Hypokalemia       | 3.0 - 3.4  | 2.5 -    | 2.0 - 2.4  | \< 2.0    |
|                   | mEq/L      | 2.9      | mEq/L      | mEq/L or  |
|                   |            | mEq/L    |            | abnormal  |
|                   |            |          | or         | potassium |
|                   |            |          | intensive  | *with*    |
|                   |            |          | r          |           |
|                   |            |          | eplacement | paresis,  |
|                   |            |          | therapy or | ileus or  |
|                   |            |          | hospi      | life-th   |
|                   |            |          | talization | reatening |
|                   |            |          | required   | a         |
|                   |            |          |            | rrhythmia |
+-------------------+------------+----------+------------+-----------+
| Hyperkalemia      | 5.6 - 6.0  | 6.1 -    | 6.6 - 7.0  | \> 7.0    |
|                   | mEq/L      | 6.5      | mEq/l      | mEq/L     |
|                   |            | mEq/L    |            |           |
|                   |            |          |            | or        |
|                   |            |          |            | abnormal  |
|                   |            |          |            | potassium |
|                   |            |          |            | *with*    |
|                   |            |          |            | life-th   |
|                   |            |          |            | reatening |
|                   |            |          |            | a         |
|                   |            |          |            | rrhythmia |
+-------------------+------------+----------+------------+-----------+
| Hypoglycemia      | 55-64      | 40-54    | 30-39      | \<30      |
|                   | mg/dL      | mg/dL    | mg/dL      | mg/dL or  |
|                   |            |          |            | abnormal  |
|                   |            |          |            | glucose   |
|                   |            |          |            | *with*    |
|                   |            |          |            | mental    |
|                   |            |          |            | status    |
|                   |            |          |            | changes   |
|                   |            |          |            | or coma   |
+-------------------+------------+----------+------------+-----------+
| Hyperglycemia     | 116 - 160  | 161- 250 | 251 - 500  | \> 500    |
|                   | mg/dL      | mg/dL    | mg/dL      | mg/dL or  |
| (nonfasting and   |            |          |            | abnormal  |
| no prior          |            |          |            | glucose   |
| diabetes)         |            |          |            | *with*    |
|                   |            |          |            | ket       |
|                   |            |          |            | oacidosis |
|                   |            |          |            |           |
|                   |            |          |            | or        |
|                   |            |          |            | seizures  |
+-------------------+------------+----------+------------+-----------+
| Hypocalcemia      | 8.4 - 7.8  | 7.7 -    | 6.9 - 6.1  | \< 6.1    |
|                   | mg/dL      | 7.0      | mg/dL      | mg/dL     |
| (corrected for    |            | mg/dL    |            |           |
| albumin)          |            |          |            | or        |
|                   |            |          |            | abnormal  |
|                   |            |          |            | calcium   |
|                   |            |          |            | *with*    |
|                   |            |          |            | life      |
|                   |            |          |            | th        |
|                   |            |          |            | reatening |
|                   |            |          |            | a         |
|                   |            |          |            | rrhythmia |
|                   |            |          |            | or tetany |
+-------------------+------------+----------+------------+-----------+

+-------------------+------------+----------+------------+-----------+
| **CHEMISTRIES     |            |          |            |           |
| (continued)**     |            |          |            |           |
+-------------------+------------+----------+------------+-----------+
|                   | Grade 1    | Grade 2  | Grade 3    | Grade 4   |
+-------------------+------------+----------+------------+-----------+
| Hypercalcemia     | 10.6 -     | 11.6 -   | 12.6 -     | \> 13.5   |
|                   | 11.5 mg/dL | 12.5     | 13.5 mg/dL | mg/dL or  |
| (correct for      |            | mg/dL    |            | abnormal  |
| albumin)          |            |          |            | calcium   |
|                   |            |          |            | *with*    |
|                   |            |          |            | life      |
|                   |            |          |            |           |
|                   |            |          |            | th        |
|                   |            |          |            | reatening |
|                   |            |          |            |           |
|                   |            |          |            | a         |
|                   |            |          |            | rrhythmia |
+-------------------+------------+----------+------------+-----------+
| Hypomagnesemia    | 1.4 - 1.2  | 1.1 -    | 0.8 - 0.6  | \< 0.6    |
|                   | mEq/L      | 0.9      | mEq/L      | mEq/L or  |
|                   |            | mEq/L    |            | abnormal  |
|                   |            |          |            | magnesium |
|                   |            |          |            | *with*    |
|                   |            |          |            | life-th   |
|                   |            |          |            | reatening |
|                   |            |          |            | a         |
|                   |            |          |            | rrhythmia |
+-------------------+------------+----------+------------+-----------+
| Hypophosphatemia  | 2.0 - 2.4  | 1.5 -1.9 | 1.0 -1.4   | \< 1.0    |
|                   | mg/dL      | mg/dL or | mg/dL      | mg/dL or  |
|                   |            |          |            | abnormal  |
|                   |            | rep      | intensive  | phosphate |
|                   |            | lacement | therapy    | *with*    |
|                   |            | Rx       |            | life-th   |
|                   |            | required | or         | reatening |
|                   |            |          |            | a         |
|                   |            |          | hospi      | rrhythmia |
|                   |            |          | talization |           |
|                   |            |          | required   |           |
+-------------------+------------+----------+------------+-----------+
| H                 | 1.1 -      | 1.25 -   | 1.5 --     | \> 1.75 x |
| yperbilirubinemia | \<1.25 x   | \<1.5 x  | 1.75 x ULN | ULN       |
| (when accompanied | ULN        | ULN      |            |           |
| by any increase   |            |          |            |           |
| in other liver    |            |          |            |           |
| function test)    |            |          |            |           |
+-------------------+------------+----------+------------+-----------+
| H                 | 1.1 -      | 1.5 -    | 2.0 -- 3.0 | \> 3.0 x  |
| yperbilirubinemia | \<1.5 x    | \<2.0 x  | x ULN      | ULN       |
| (when other liver | ULN        | ULN      |            |           |
| function are in   |            |          |            |           |
| the normal range) |            |          |            |           |
+-------------------+------------+----------+------------+-----------+
| BUN               | 1.25 - 2.5 | 2.6 - 5  | 5.1 - 10 x | \> 10 x   |
|                   | x ULN      | x ULN    | ULN        | ULN       |
+-------------------+------------+----------+------------+-----------+
| Hyperuricemia     | 7.5 --     | 10.1 --  | 12.1 --    | \>15.0    |
| (uric acid)       | 10.0 mg/dL | 12.0     | 15.0 mg/dL | mg/dL     |
|                   |            | mg/dL    |            |           |
+-------------------+------------+----------+------------+-----------+
| Creatinine        | 1.1 - 1.5  | 1.6 -    | 3.1 - 6 x  | \> 6 x    |
|                   | x ULN      | 3.0 x    | ULN        | ULN or    |
|                   |            | ULN      |            |           |
|                   |            |          |            | dialysis  |
|                   |            |          |            | required  |
+-------------------+------------+----------+------------+-----------+

+-------------------+-----------+-----------+-----------+-----------+
| ### ENZYMES       |           |           |           |           |
+-------------------+-----------+-----------+-----------+-----------+
| ###               | Grade 1   | Grade 2   | Grade 3   | Grade 4   |
+-------------------+-----------+-----------+-----------+-----------+
| AST (SGOT)        | 1.1 -     | 2.0 --    | 3.0 --    | \> 8 x    |
|                   | \<2.0 x   | \<3.0 x   | 8.0 x ULN | ULN       |
|                   | ULN       | ULN       |           |           |
+-------------------+-----------+-----------+-----------+-----------+
| ALT (SGPT)        | 1.1 -     | 2.0 --    | 3.0 --    | \> 8 x    |
|                   | \<2.0 x   | \<3.0 x   | 8.0 x ULN | ULN       |
|                   | ULN       | ULN       |           |           |
+-------------------+-----------+-----------+-----------+-----------+
| GGT               | 1.1 -     | 2.0 --    | 3.0 --    | \> 8 x    |
|                   | \<2.0 x   | \<3.0 x   | 8.0 x ULN | ULN       |
|                   | ULN       | ULN       |           |           |
+-------------------+-----------+-----------+-----------+-----------+
| Alkaline          | 1.1 -     | 2.0 --    | 3.0 --    | \> 8 x    |
| Phosphatase       | \<2.0 x   | \<3.0 x   | 8.0 x ULN | ULN       |
|                   | ULN       | ULN       |           |           |
+-------------------+-----------+-----------+-----------+-----------+
| Amylase           | 1.1 - 1.5 | 1.6 - 2.0 | 2.1 - 5.0 | \> 5.1 x  |
|                   | x ULN     | x ULN     | x ULN     | ULN       |
+-------------------+-----------+-----------+-----------+-----------+
| Lipase            | 1.1 - 1.5 | 1.6 - 2.0 | 2.1 - 5.0 | \> 5.1 x  |
|                   | x ULN     | x ULN     | x ULN     | ULN       |
+-------------------+-----------+-----------+-----------+-----------+

+-------------------+------------+----------+------------+-----------+
| ### URINALYSIS    |            |          |            |           |
+-------------------+------------+----------+------------+-----------+
| ###               | Grade 1    | Grade 2  | Grade 3    | Grade 4   |
+-------------------+------------+----------+------------+-----------+
| Proteinuria       | 1+         | 2-3+     | 4+         | nephrotic |
|                   |            |          |            | syndrome  |
|                   | or         | or       | or         |           |
|                   |            |          |            | or        |
|                   | 200 mg - 1 | 1- 2 gm  | 2-3.5 gm   |           |
|                   | gm         | loss/day | loss/day   | \> 3.5 gm |
|                   | loss/day   |          |            | loss/day  |
+-------------------+------------+----------+------------+-----------+
| Hematuria         | m          | gross,   | gross,     | ob        |
|                   | icroscopic | no clots | with or    | structive |
|                   | only       |          | without    | or        |
|                   |            | \>10     | clots, OR  | required  |
|                   | \<10       | rbc/hpf  | red blood  | tr        |
|                   | rbc/hpf    |          | cell casts | ansfusion |
+-------------------+------------+----------+------------+-----------+

+-------------------+------------+----------+------------+-----------+
| *                 |            |          |            |           |
| *CARDIOVASCULAR** |            |          |            |           |
+-------------------+------------+----------+------------+-----------+
| ###               | Grade 1    | Grade 2  | Grade 3    | Grade 4   |
+-------------------+------------+----------+------------+-----------+
| Cardiac Rhythm    |            | asymp    | r          | unstable  |
|                   |            | tomatic, | ecurrent/p | dy        |
|                   |            | t        | ersistent; | srythmia; |
|                   |            | ransient |            | hospit    |
|                   |            | signs,   | s          | alization |
|                   |            | no       | ymptomatic | and       |
|                   |            |          | Rx         | treatment |
|                   |            | Rx       | required   | required  |
|                   |            | required |            |           |
+-------------------+------------+----------+------------+-----------+
| Hypertension      | transient  | re       | acute      | end organ |
|                   | increase   | current, | treatment  | damage or |
|                   |            | chronic  | required;  | hospit    |
|                   | \> 20      | increase | outpatient | alization |
|                   | mm/Hg; no  |          | treatment  | required  |
|                   | treatment  | \>       | or         |           |
|                   |            | 20mm/Hg. | hospi      |           |
|                   |            |          | talization |           |
|                   |            | /t       | possible   |           |
|                   |            | reatment |            |           |
|                   |            | required |            |           |
+-------------------+------------+----------+------------+-----------+
| Hypotension       | transient  | symptoms | requires   | mean      |
|                   | o          | due to   | IV fluids; | arterial  |
|                   | rthostatic | ort      | no         | pressure  |
|                   | h          | hostatic | hospi      |           |
|                   | ypotension | hyp      | talization | \<60mm/   |
|                   | with heart | otension | required   | Hg or end |
|                   | rate       | or BP    |            | organ     |
|                   | increased  | d        |            | damage or |
|                   | by \<20    | ecreased |            | shock;    |
|                   | beat/min   | by \<20  |            | requires  |
|                   | or         | mm Hg    |            | hospit    |
|                   | decreased  | s        |            | alization |
|                   | by \<10 mm | ystolic; |            | and       |
|                   | Hg         | cor      |            | va        |
|                   | systolic   | rectable |            | sopressor |
|                   | BP, No     | with     |            | treatment |
|                   | treatment  | oral     |            |           |
|                   | required   | fluid    |            |           |
|                   |            | t        |            |           |
|                   |            | reatment |            |           |
+-------------------+------------+----------+------------+-----------+
| Pericarditis      | minimal    | mild/    | s          | t         |
|                   | effusion   | moderate | ymptomatic | amponade; |
|                   |            | asym     | effusion;  | pericardi |
|                   |            | ptomatic | pain; EKG  | ocentesis |
|                   |            | e        | changes    | or        |
|                   |            | ffusion, |            | surgery   |
|                   |            | no       |            | required  |
|                   |            | t        |            |           |
|                   |            | reatment |            |           |
+-------------------+------------+----------+------------+-----------+
| Hemorrhage, Blood | microsco   | mild, no | gross      | massive   |
| Loss              | pic/occult | tra      | blood      | blood     |
|                   |            | nsfusion | loss;      | loss; \>  |
|                   |            |          |            | 3 units   |
|                   |            |          | 1-2 units  | t         |
|                   |            |          | transfused | ransfused |
+-------------------+------------+----------+------------+-----------+

+-------------------+------------+----------+------------+-----------+
| ### RESPIRATORY   |            |          |            |           |
+-------------------+------------+----------+------------+-----------+
| ###               | Grade 1    | Grade 2  | Grade 3    | Grade 4   |
+-------------------+------------+----------+------------+-----------+
| Cough             | transient- | pe       | Paroxysmal | \-\       |
|                   | no         | rsistent | cough;     | -\-\-\-\- |
|                   | treatment  | cough;   | un         | \-\-\-\-\ |
|                   |            |          | controlled | -\-\-\-\- |
|                   |            | t        | with       | \-\-\-\-- |
|                   |            | reatment | treatment  |           |
|                   |            | re       |            |           |
|                   |            | sponsive |            |           |
+-------------------+------------+----------+------------+-----------+
| Bronchospasm,     | transient; | requires | no         | cyanosis: |
| Acute             | no         | tr       | nor        | FEV~1~    |
|                   | treatment; | eatment; | malization |           |
|                   |            | no       | with       | \< 25%    |
|                   | 70% - 80%  | rmalizes | bronc      |           |
|                   | FEV~1~     | with     | hodilator; | of peak   |
|                   |            | broncho  |            | flow or   |
|                   | of peak    | dilator; | FEV~1~     | i         |
|                   | flow       |          | 25% - 50%  | ntubation |
|                   |            | FEV~1~   |            | necessary |
|                   |            | 50% -    | of peak    |           |
|                   |            | 70%      | flow; or   |           |
|                   |            |          | r          |           |
|                   |            | (of peak | etractions |           |
|                   |            | flow)    | present    |           |
+-------------------+------------+----------+------------+-----------+
| Dyspnea           | dyspnea on | dyspnea  | dyspnea at | dyspnea   |
|                   | exertion   | with     | rest       | requiring |
|                   |            | normal   |            | Oxygen    |
|                   |            | activity |            | therapy   |
+-------------------+------------+----------+------------+-----------+

+-------------------+------------+----------+------------+-----------+
| **G               |            |          |            |           |
| ASTROINTESTINAL** |            |          |            |           |
+-------------------+------------+----------+------------+-----------+
| ###               | Grade 1    | Grade 2  | Grade 3    | Grade 4   |
+-------------------+------------+----------+------------+-----------+
| Nausea            | mild or    | moderate | no         | hospit    |
|                   | transient; | dis      | s          | alization |
|                   | maintains  | comfort; | ignificant | required; |
|                   | reasonable | intake   | intake;    |           |
|                   | intake     | d        | requires   |           |
|                   |            | ecreased | IV fluids  |           |
|                   |            | signif   |            |           |
|                   |            | icantly; |            |           |
|                   |            | some     |            |           |
|                   |            | activity |            |           |
|                   |            | limited  |            |           |
+-------------------+------------+----------+------------+-----------+
| Vomiting          | 1 episode  | 2-5      | \>6        | ph        |
|                   | in 24      | episodes | episodes   | ysiologic |
|                   | hours      | in 24    | in 24      | con       |
|                   |            | hours    | hours or   | sequences |
|                   |            |          | needing IV | requiring |
|                   |            |          | fluids     | hospit    |
|                   |            |          |            | alization |
|                   |            |          |            | or        |
|                   |            |          |            | requiring |
|                   |            |          |            | p         |
|                   |            |          |            | arenteral |
|                   |            |          |            | nutrition |
+-------------------+------------+----------+------------+-----------+
| Constipation      | requiring  | r        | o          | ob        |
|                   | stool      | equiring | bstipation | struction |
|                   | softener   | l        | requiring  | or toxic  |
|                   | or dietary | axatives | manual     | megacolon |
|                   | mo         |          | evacuation |           |
|                   | dification |          | or enema   |           |
+-------------------+------------+----------+------------+-----------+
| Diarrhea          | mild or    | moderate | \>7 loose  | hy        |
|                   | transient; | or       | stools/day | potensive |
|                   | 3-4 loose  | per      | or bloody  | shock or  |
|                   | stools/day | sistent; | diarrhea;  | ph        |
|                   | or mild    | 5-7      | or         | ysiologic |
|                   | diarrhea   | loose    | o          | con       |
|                   | last \< 1  | st       | rthostatic | sequences |
|                   | week       | ools/day | h          | requiring |
|                   |            | or       | ypotension | hospit    |
|                   |            | diarrhea | or         | alization |
|                   |            | lasting  | e          |           |
|                   |            | \>1 week | lectrolyte |           |
|                   |            |          | imbalance  |           |
|                   |            |          | or \>2L IV |           |
|                   |            |          | fluids     |           |
|                   |            |          | required   |           |
+-------------------+------------+----------+------------+-----------+
| Oral              | mild       | some     | eati       | unable to |
| Dis               | d          | limits   | ng/talking | drink     |
| comfort/Dysphagia | iscomfort; | on       | very       | fluids;   |
|                   | no         | eating/  | limited;   | requires  |
|                   | difficulty | drinking | unable to  | IV fluids |
|                   | swallowing |          | swallow    |           |
|                   |            |          | solid      |           |
|                   |            |          | foods      |           |
+-------------------+------------+----------+------------+-----------+

+-------------------+------------+----------+------------+-----------+
| **NEUROLOGICAL**  |            |          |            |           |
+-------------------+------------+----------+------------+-----------+
| ###               | Grade 1    | Grade 2  | Grade 3    | Grade 4   |
+-------------------+------------+----------+------------+-----------+
| Neuro-Cerebellar  | slight     | i        | locomotor  | inca      |
|                   | inco       | ntention | ataxia     | pacitated |
|                   | ordination | tremor,  |            |           |
|                   | dysdiado   | dy       |            |           |
|                   | chokinesis | smetria, |            |           |
|                   |            | slurred  |            |           |
|                   |            | speech;  |            |           |
|                   |            | n        |            |           |
|                   |            | ystagmus |            |           |
+-------------------+------------+----------+------------+-----------+
| Psychiatric       | mild       | moderate | severe     | acute     |
|                   | anxiety or | anxiety  | mood       | psychosis |
|                   | depression | or       | changes    | requiring |
|                   |            | dep      | requiring  | hospita   |
|                   |            | ression; | therapy;   | lization; |
|                   |            | therapy  | or         | or        |
|                   |            | r        | suicidal   | suicidal  |
|                   |            | equired; | ideation;  | gestur    |
|                   |            | change   | or         | e/attempt |
|                   |            | in       | aggressive | or        |
|                   |            | normal   | ideation   | hallu     |
|                   |            | routine  |            | cinations |
+-------------------+------------+----------+------------+-----------+
| Muscle Strength   | subjective | mild     | objective  | paralysis |
|                   | weakness   | o        | weakness   |           |
|                   |            | bjective | function   |           |
|                   | no         |          | limited    |           |
|                   | objective  | signs/   |            |           |
|                   | symptoms/  | symptoms |            |           |
|                   | signs      |          |            |           |
|                   |            | no       |            |           |
|                   |            | decrease |            |           |
|                   |            | in       |            |           |
|                   |            | function |            |           |
+-------------------+------------+----------+------------+-----------+
| Paresthesia       | mild       | moderate | severe     | incapa    |
| (burning,         | d          | dis      | d          | citating; |
| tingling, etc.)   | iscomfort; | comfort; | iscomfort; | or not    |
|                   | no         | non-     | or         | r         |
|                   | treatment  | narcotic | narcotic   | esponsive |
|                   | required   | a        | analgesia  | to        |
|                   |            | nalgesia | required   | narcotic  |
|                   |            | required | with       | analgesia |
|                   |            |          | s          |           |
|                   |            |          | ymptomatic |           |
|                   |            |          | i          |           |
|                   |            |          | mprovement |           |
+-------------------+------------+----------+------------+-----------+
| Neuro-sensory     | mild       | moderate | severe     | sensory   |
|                   | impairment | im       | impairment | loss      |
|                   | in         | pairment | (decreased | involves  |
|                   | sensation  | (mod     | or loss of | limbs and |
|                   | (decreased | d        | sensation  | trunk;    |
|                   | sensation, | ecreased | to knees   | p         |
|                   | e.g.,      | se       | or wrists) | aralysis; |
|                   | vibratory, | nsation, | or loss of | or        |
|                   | pinprick,  | e.g.,    | sensation  | seizures  |
|                   | hot/cold   | vi       | of at      |           |
|                   | in great   | bratory, | least mod  |           |
|                   | toes) in   | p        | degree in  |           |
|                   | focal area | inprick, | multiple   |           |
|                   | or         | hot/cold | different  |           |
|                   | s          | to       | body areas |           |
|                   | ymmetrical | ankles)  | (i.e.,     |           |
|                   | dis        | and/or   | upper and  |           |
|                   | tribution; | joint    | lower      |           |
|                   | or change  | position | ex         |           |
|                   | in taste,  | or mild  | tremities) |           |
|                   | smell,     | im       |            |           |
|                   | vision     | pairment |            |           |
|                   | and/or     | that is  |            |           |
|                   | hearing    | not      |            |           |
|                   |            | sym      |            |           |
|                   |            | metrical |            |           |
+-------------------+------------+----------+------------+-----------+

+-------------------+------------+----------+------------+-----------+
| **                |            |          |            |           |
| MUSCULOSKELATEL** |            |          |            |           |
+-------------------+------------+----------+------------+-----------+
| ###               | Grade 1    | Grade 2  | Grade 3    | Grade 4   |
+-------------------+------------+----------+------------+-----------+
| ### Arthralgia    | mild pain  | moderate | severe     | disabling |
|                   | not        | pain,    | pain; pain | pain      |
| (joint pain)      | i          | an       | and/or     |           |
|                   | nterfering | algesics | analgesics |           |
|                   | with       | and/or   | i          |           |
|                   | function   | pain     | nterfering |           |
|                   |            | int      | with       |           |
|                   |            | erfering | activities |           |
|                   |            | with     | of daily   |           |
|                   |            | function | living     |           |
|                   |            | but not  |            |           |
|                   |            | with     |            |           |
|                   |            | ac       |            |           |
|                   |            | tivities |            |           |
|                   |            | of daily |            |           |
|                   |            | living   |            |           |
+-------------------+------------+----------+------------+-----------+
| Arthritis         | mild pain  | moderate | severe     | permanent |
|                   | with       | pain     | pain with  | and/or    |
|                   | inf        | with     | inf        | disabling |
|                   | lammation, | infla    | lammation, | joint     |
|                   | erythema   | mmation, | erythema   | di        |
|                   | or joint   | erythema | or joint   | struction |
|                   | swelling   | or joint | swelling   |           |
|                   | -- but not | swelling | --and      |           |
|                   | i          | --       | i          |           |
|                   | nterfering | int      | nterfering |           |
|                   | with       | erfering | with       |           |
|                   | function   | with     | activities |           |
|                   |            | f        | of daily   |           |
|                   |            | unction, | living     |           |
|                   |            | but not  |            |           |
|                   |            | with     |            |           |
|                   |            | ac       |            |           |
|                   |            | tivities |            |           |
|                   |            | of daily |            |           |
|                   |            | living   |            |           |
+-------------------+------------+----------+------------+-----------+
| Myalgia           | myalgia    | muscle   | severe     | frank     |
|                   | with no    | te       | muscle     | my        |
|                   | limitation | nderness | tenderness | onecrosis |
|                   | of         | (at      | with       |           |
|                   |            | other    | marked     |           |
|                   | activity   | than     | impairment |           |
|                   |            | i        | of         |           |
|                   |            | njection | activity   |           |
|                   |            | site) or |            |           |
|                   |            | with     |            |           |
|                   |            | moderate |            |           |
|                   |            | im       |            |           |
|                   |            | pairment |            |           |
|                   |            | of       |            |           |
|                   |            | activity |            |           |
+-------------------+------------+----------+------------+-----------+

+-------------------+------------+----------+------------+-----------+
| **SKIN**          |            |          |            |           |
+-------------------+------------+----------+------------+-----------+
| ###               | Grade 1    | Grade 2  | Grade 3    | Grade 4   |
+-------------------+------------+----------+------------+-----------+
| Mucocutaneous     | erythema;  | diffuse, | ve         | ex        |
|                   | pruritus   | maculo   | siculation | foliative |
|                   |            | papular  | or moist   | de        |
|                   |            | rash,    | de         | rmatitis, |
|                   |            | dry      | squamation | mucous    |
|                   |            | desq     | or         | membrane  |
|                   |            | uamation | ulceration | in        |
|                   |            |          |            | volvement |
|                   |            |          |            | or        |
|                   |            |          |            | erythema, |
|                   |            |          |            | m         |
|                   |            |          |            | ultiforme |
|                   |            |          |            | or        |
|                   |            |          |            | suspected |
|                   |            |          |            | Steven    |
|                   |            |          |            | s-Johnson |
|                   |            |          |            | or        |
|                   |            |          |            | necrosis  |
|                   |            |          |            | requiring |
|                   |            |          |            | surgery   |
+-------------------+------------+----------+------------+-----------+
| Induration        | **\<**     | 15-30 mm | \>30mm     |           |
|                   | 15mm       |          |            |           |
+-------------------+------------+----------+------------+-----------+
| Erythema          | **\<**     | 15-30 mm | \>30mm     |           |
|                   | 15mm       |          |            |           |
+-------------------+------------+----------+------------+-----------+
| Edema             | **\<**     | 15-30 mm | \>30mm     |           |
|                   | 15mm       |          |            |           |
+-------------------+------------+----------+------------+-----------+
| Rash at Injection | **\<**     | 15-30 mm | \>30mm     |           |
| Site              | 15mm       |          |            |           |
+-------------------+------------+----------+------------+-----------+
| Pruritus          | slight     | moderate | itching    |           |
|                   | itching at | itching  | over       |           |
|                   | injection  | at       | entire     |           |
|                   | site       | i        | body       |           |
|                   |            | njection |            |           |
|                   |            | e        |            |           |
|                   |            | xtremity |            |           |
+-------------------+------------+----------+------------+-----------+

+-------------------+------------+----------+------------+-----------+
| **SYSTEMIC**      |            |          |            |           |
+-------------------+------------+----------+------------+-----------+
| ###               | Grade 1    | Grade 2  | Grade 3    | Grade 4   |
+-------------------+------------+----------+------------+-----------+
| Allergic Reaction | pruritus   | l        | g          | an        |
|                   | without    | ocalized | eneralized | aphylaxis |
|                   | rash       | u        | urticaria; |           |
|                   |            | rticaria | angioedema |           |
+-------------------+------------+----------+------------+-----------+
| Headache          | mild, no   | tr       | severe;    | int       |
|                   | treatment  | ansient, | responds   | ractable; |
|                   | required   | m        | to initial | requires  |
|                   |            | oderate; | narcotic   | repeated  |
|                   |            | t        | therapy    | narcotic  |
|                   |            | reatment |            | therapy   |
|                   |            | required |            |           |
+-------------------+------------+----------+------------+-----------+
| Fever: oral       | 37.7 -     | 38.6 -   | 39.6 -     | \> 40 C   |
|                   | 38.5 C or  | 39.5 C   | 40.5 C or  | or        |
|                   |            | or       |            |           |
|                   | 100.0 -    |          | 103 - 105  | \> 105 F  |
|                   | 101.5 F    | 101.6 -  | F          |           |
|                   |            | 102.9 F  |            |           |
+-------------------+------------+----------+------------+-----------+
| Fatigue           | normal     | normal   | normal     | unable to |
|                   | activity   | activity | activity   | care for  |
|                   | reduced \< | d        | decreased  | self      |
|                   | 48 hours   | ecreased | \> 50%     |           |
|                   |            | 25- 50%  | can't work |           |
|                   |            | \> 48    |            |           |
|                   |            | hours    |            |           |
+-------------------+------------+----------+------------+-----------+