Use of Safety Monitoring Flow Sheets

Background  Flow sheets can serve as useful tools  Not required but recommended  Tailor for ease of use AND usefulness at your site  When tailoring, consider staff roles and responsibilities AND other documentation requirements at your site

Flow Sheets  Height and weight  Vital signs  Hematology  Liver function: ALT and AST  Renal function: phosphate and creatinine

Common Elements Title Brief instructions/guidance Date and visit code Values being monitored Shading indicates “not applicable” Staff Initials

General Instructions for Use  Initiate use during screening  File for “easy access” in participant study notebook  Update at or after each visit  Continually review as part of ongoing safety monitoring  Initial and date to document reviews

Height  Why are there two rows to record height on each date?

Height  Because the protocol requires repeat measurement if a decrease of 3.8 cm or more is identified  Record NA if a second measurement is not required and therefore is not done  Severity grading is not required

Weight  Why is percentage difference from Screening Part 2 needed?

Weight  Because the severity of unintentional weight loss must be graded in terms of percent decrease 01 JAN JAN APR (M3) % 50 – 45 = 5 5 ÷ 50 = 0.10 = 10%

Vital Signs  Fever (oral temp), hypertension, and hypotension must be graded  For hypertension, grading requires repeat blood pressure measurement at the same visit

Hematology

 Hemoglobin, platelets, white blood cells, neutrophils, and lymphocytes must be graded  Hemoglobin is graded based on absolute values and difference from Screening Part 1  Neutrophils and lymphocytes are graded based on absolute counts  Although not recorded on flow sheet, abnormal differential counts should also be monitored for clinical significance

 All results should be graded  Grading is based on the site upper limit of normal (record at top of flow sheet for ease of reference) ALT and AST

Phosphate  All results should be graded  Grading is based on the site lower limit of normal (record at top of flow sheet for ease of reference)

Creatinine

 Absolute levels must be graded (based on site upper limit of normal)  Increases from baseline must be calculated to determine whether product hold is required  Creatinine clearance rate must be calculated to determine whether product hold is required

Creatinine: Relative Increase From Baseline 01 JAN APR (M3) 0.8 mg/dL0.9 mg/dL mg/dL 0.8 mg/dL mL/min87 mL/min 0.9 ÷ 0.8 = 1.1  Participant is a 23 year old, 57 kg woman, oral study product

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