Examples: Tables. Descriptive stats with ANOVA, ANCOVA, and t test p values Frequency and percent Correlation coefficients

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2 Examples: Tables Descriptive stats with ANOVA, ANCOVA, and t test p values Frequency and percent Correlation coefficients

3 Descriptive Statistics Table 1. Body Mass Index using Last Observation Carried Forward Visit Baseline Week 6 Statistics N Mean Median (etc.) N Mean Median (etc.) p value (3) Active (N=xx) xx xx.x xx xx.x Observed Placebo (N=xx) xx xx.x xx xx.x Active (N=xx) xx xx.x x.xxxx Change from Baseline Placebo (N=xx) xx xx.x x.xxxx (1) ANOVA model: response = Treatment Group + Study Center. (2) ANCOVA model: change = Baseline + Treatment Group + Study Center. (3) Paired t test for change from baseline within Treatment Group. Treatment Group Comparison (p value) x.xxxx (1) x.xxxx (2)

4 Incidence Table 2. Incidence of Body Weight Loss, Baseline to Week 12 Visit / Outcome Statistics Active (N=xx) Placebo (N=xx) Week 12 Body Weight Loss No Body Weight Loss N (pct) xx (xxx.x) xx (xxx.x)

5 Correlations Table 3. Correlation Coefficients for Weight/BMI with Dietary Intake Change from Baseline to End of Study Change from Baseline to End of Study Active Correlation N Placebo Correlation N Weight (kg) Total calories (kcal) Carbohydrate (g) (etc.) Body Mass Index Total calories (kcal) Carbohydrate (g) (etc.) Body Mass Index % of Calories from Carbohydrate (etc.)

6 SDTM Files Vital Signs: Height and Weight (VS) Food Frequency Questionnaire: dietary intake and analysis (QS)

7 SDTM Files: VS USUBJID VISIT VSTESTCD VSSTRESN VSSTAT BASELINE HEIGHT xx BASELINE WEIGHT xx WEEK 6 HEIGHT xx WEEK 6 WEIGHT xx WEEK 12 WEIGHT xx WEEK 12 HEIGHT. NOT DONE

8 SDTM Files: QS QSCAT = [name of questionnaire] QSSCAT QSTESTCD QSTEST QSORRES QSSTRESN VISIT Raw Questionnaire Response COLDCFR Cold cereal, Freq last wk 3 4 DAYS LAST WEEK 4 BASELINE Raw Questionnaire Response COLDCQU Cold cereal, Quan each 1 BOWL 2 BASELINE Dietary Analysis Dietary Analysis TOTCAL Total calories BASELINE CARB Carbohydrate BASELINE

9 Plan for ADaM File ADDIET Include nonmissing VSSTRESN, QSSTRESN Calculate BMI = [weight (kg)] / [height (m)] 2 Calculate percent of total calories from carbohydrate, fat, protein

10 Compute BMI AVISIT PARAMCD PARAMTYP SRCDOM SRCVAR SRCSEQ Baseline HEIGHT VS VSSTRESN xx Baseline WEIGHT VS VSSTRESN xx Baseline BMI DERIVED Week 6 HEIGHT VS VSSTRESN xx Week 6 WEIGHT VS VSSTRESN xx Week 6 BMI DERIVED

11 Compute PCTCARB AVISIT PARAMCD PARAMTYP SRCDOM SRCVAR SRCSEQ Baseline CARB QS QSSTRESN xx Baseline TOTCAL QS QSSTRESN xx Baseline PCTCARB DERIVED Week 6 CARB QS QSSTRESN xx Week 6 TOTCAL QS VSSTRESN xx Week 6 PCTCARB DERIVED

12 Parameters PARAM PARAMCD PARAMTYP Body Mass Index BMI DERIVED Carbohydrate (grams) CARB Height (cm) HEIGHT % of Calories from Carbohydrate PCTCARB DERIVED % of Calories from Fat PCTFAT DERIVED % of Calories from Protein PCTPROT DERIVED Total calories (kcal) TOTCAL Weight (kg) WEIGHT

13 Baseline flag AVISIT PARAMCD PARAMTYP ABLFL Baseline BMI DERIVED Y Baseline CARB Y Baseline HEIGHT Y Baseline PCTCARB DERIVED Y Baseline TOTCAL Y Baseline WEIGHT Y

14 Compute LOCF BMI AVISIT VISIT PARAMCD PARAMTYP DTYPE SRCDOM SRCVAR SRCSEQ Baseline BASELINE BMI DERIVED Week 6 WEEK 6 BMI DERIVED Week 12 WEEK 6 BMI DERIVED LOCF

15 Average Over Visits AVISIT PARAMCD PARAMTYP DTYPE SRCDOM SRCVAR SRCSEQ Post Baseline CARB AVERAGE Post Baseline PCTCARB DERIVED AVERAGE Post Baseline TOTCAL AVERAGE

16 Dietary Parameters AVISIT PARAMCD PARAMTYP DTYPE SRCDOM SRCVAR SRCSEQ Baseline CARB QS QSSTRESN xx Baseline TOTCAL QS QSSTRESN xx Baseline PCTCARB DERIVED Week 6 CARB QS QSSTRESN xx Week 6 TOTCAL QS QSSTRESN xx Week 6 PCTCARB DERIVED Week 12 CARB QS QSSTRESN xx Week 12 TOTCAL QS QSSTRESN xx Week 12 PCTCARB DERIVED Post Baseline CARB AVERAGE Post Baseline PCTCARB DERIVED AVERAGE Post Baseline TOTCAL AVERAGE

17 AVAL, BASE, CHG AVISIT PARAMCD AVAL BASE CHG ABLFL Baseline BMI x.x x.x Y Baseline HEIGHT x.x x.x Y Baseline CARB x.x x.x Y Baseline TOTCAL x.x x.x Y Baseline PCTCARB x.x x.x Y Baseline WEIGHT x.x x.x Y Week 6 BMI x.x x.x x.x Week 6 HEIGHT x.x x.x x.x Week 6 CARB x.x x.x x.x Week 6 TOTCAL x.x x.x x.x Week 6 PCTCARB x.x x.x x.x Week 6 WEIGHT x.x x.x x.x

18 Descriptive Statistics Table 1. Body Mass Index using Last Observation Carried Forward Visit Baseline Week 6 Statistics N Mean Median (etc.) N Mean Median (etc.) p value (3) Active (N=xx) xx xx.x xx xx.x Observed Placebo (N=xx) xx xx.x xx xx.x Active (N=xx) xx xx.x x.xxxx Change from Baseline Placebo (N=xx) xx xx.x x.xxxx (1) ANOVA model: response = Treatment Group + Study Center. (2) ANCOVA model: change = Baseline + Treatment Group + Study Center. (3) Paired t test for change from baseline within Treatment Group. Treatment Group Comparison (p value) x.xxxx (1) x.xxxx (2)

19 Results Metadata: Table 1 Display Identifier: Table 1 Display Name: Table 1. Body Mass Index using Last Observation Carried Forward Result Identifier Param Paramcd Analysis Variable Dataset Selection Criteria Documentation Programming Statements (SAS ) Observed baseline Treatment Group Comparison p value Body Mass Index BMI AVAL ADDIET AVISITN = 0 and ITTFL = Y Use Type III sums of squares for all models, and pooled site number proc glm; class trtpn sitegr1n; model aval = trtpn sitegr1n; Observed postbaseline LS means Body Mass Index BMI AVAL ADDIET AVISITN > 0 and ITTFL = Y proc glm; by avisitn; class trtpn sitegr1n; model aval = base trtpn sitegr1n; lsmeans trtpn;

20 Results Metadata: Table 1 Display Identifier: Table 1 Display Name: Table 1. Body Mass Index using Last Observation Carried Forward Result Identifier Param Paramcd Analysis Variable Dataset Selection Criteria Document ation Programming Statements (SAS ) Change LS means and Treatment Group Comparison p value (footnote 2) Body Mass Index BMI CHG ADDIET AVISITN > 0 and ITTFL = Y Model with no interaction terms proc glm; by avisitn; class trtpn sitegr1n; model chg = base trtpn sitegr1n; lsmeans trtpn; p value (footnote 3) Body Mass Index BMI CHG ADDIET AVISITN > 0 and ITTFL = Y Paired t test proc means prt nway; class avisitn trtpn; var chg;

21 Categorize Weight Change AVISIT PARAMCD AVAL BASE CHG CHGCAT1 Baseline WEIGHT x.x x.x Week 6 WEIGHT x.x x.x 1.3 Body Weight Loss Week 12 WEIGHT x.x x.x 0.9 No Body Weight Loss

22 Incidence Table 2. Incidence of Body Weight Loss, Baseline to Week 12 Visit / Outcome Statistics Active (N=xx) Placebo (N=xx) Week 12 Body Weight Loss No Body Weight Loss N (pct) xx (xxx.x) xx (xxx.x)

23 Results Metadata: Table 2 Display Identifier: Table 2 Display Name: Incidence of Body Weight Loss, Baseline to Week 12 Result Identifier Param Paramcd Analysis Variable Weight (kg) Dataset Selection Criteria Documentation Programming Statements (SAS ) WEIGHT CHGCAT1 ADDIET ITTFL = Y and CHGCAT1N in (1,2) and AVISIT = Week 12 CHGCAT1N = 1 means body weight loss, 2 = no body weight loss.

24 Correlations Table 3. Correlation Coefficients for Weight/BMI with Dietary Intake Change from Baseline to End of Study Change from Baseline to End of Study Active Correlation N Placebo Correlation N Weight (kg) Total calories (kcal) Carbohydrate (g) (etc.) Body Mass Index Total calories (kcal) Carbohydrate (g) (etc.) Body Mass Index % of Calories from Carbohydrate (etc.)

25 Correlations: tasks Only visits where all parameters were measured (no LOCF) Change from baseline to last such postbaseline visit

26 All values measured Flag visits where all parameters measured Easy when denormalized: if nmiss(height,weight,carb,totcal) = 0 then ANL01FL = Y ; AVISIT HEIGHT WEIGHT TOTCAL CARB ANL01FL Baseline x.x x.x x.x x.x Y Week 6 x.x x.x x.x x.x Y

27 All values measured Then transpose: AVISIT PARAMCD CHG ABLFL ANL01FL Baseline CARB Y Y Baseline HEIGHT Y Y Baseline TOTCAL Y Y Baseline WEIGHT Y Y Week 6 CARB x.x Y Week 6 HEIGHT x.x Y Week 6 TOTCAL x.x Y Week 6 WEIGHT x.x Y

28 Last visit with all measured AVISIT PARAMCD CHG ABLFL ANL01FL ANL02FL Baseline CARB Y Y Baseline HEIGHT Y Y Baseline TOTCAL Y Y Baseline WEIGHT Y Y Week 6 CARB x.x Y Week 6 HEIGHT x.x Y Week 6 TOTCAL x.x Y Week 6 WEIGHT x.x Y Week 12 CARB x.x Y Y Week 12 HEIGHT x.x Y Y Week 12 TOTCAL x.x Y Y Week 12 WEIGHT x.x Y Y

29 All measured at baseline AVISIT PARAMCD CHG ABLFL ANL01FL ANL02FL ANL03FL Baseline CARB Y Y Y Baseline HEIGHT Y Y Y Baseline TOTCAL Y Y Y Baseline WEIGHT Y Y Y Week 6 CARB x.x Y Y Week 6 HEIGHT x.x Y Y Week 6 TOTCAL x.x Y Y Week 6 WEIGHT x.x Y Y Week 12 CARB x.x Y Y Y Week 12 HEIGHT x.x Y Y Y Week 12 TOTCAL x.x Y Y Y Week 12 WEIGHT x.x Y Y Y

30 All not measured at baseline AVISIT PARAMCD CHG ABLFL ANL01FL ANL02FL ANL03FL Baseline CARB Y Baseline TOTCAL Y Baseline WEIGHT Y Week 6 CARB x.x Y Week 6 HEIGHT x.x Y Week 6 TOTCAL x.x Y Week 6 WEIGHT x.x Y Week 12 CARB x.x Y Y Week 12 HEIGHT x.x Y Y Week 12 TOTCAL x.x Y Y Week 12 WEIGHT x.x Y Y

31 Record Selection ANL02FL = Y AND ANL03FL = Y AVISIT PARAMCD CHG ABLFL ANL01FL ANL02FL ANL03FL Week 12 CARB x.x Y Y Y Week 12 HEIGHT x.x Y Y Y Week 12 TOTCAL x.x Y Y Y Week 12 WEIGHT x.x Y Y Y

32 In SAS proc sort data=addiet out=tabledata; by trtp usubjid paramcd; where anl02fl = Y and anl03fl = Y ; run; proc transpose data=tabledata out=trandata; by trtp usubjid; id paramcd; var chg; run; proc corr data=trandata pearson; by trtp; var weight bmi; with totcal carb (other parameters); run;

33 Record Selection (actual) proc sql; create table main as select usubjid, trtpn, paramcd, chg from adam.addiet where ittfl = Y and anl03fl = Y and ( (avisit = Post Baseline and paramcd in ( TOTCAL, CARB, )) or (paramcd in ( BMI, WEIGHT ) and anl02fl = Y ) ) order by trtpn, usubjid, paramcd; quit;

34 Analysis File Metadata Dataset Description Structure Purpose Keys Class of Dataset ADDIET Diet and weight analysis file One record per subject per parameter per analysis visit Analysis STUDYID, USUBJID, PARAMCD, AVISIT BDS Location addiet.xpt

35 Bonus Example! VS Toxicity Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials Fever Vital Signs Tachycardia beats per minute Bradycardia beats per minute Hypertension (systolic) mm Hg Hypertension (diastolic) mm Hg Hypotension (systolic) mm Hg Respiratory rate breaths per minute Mild (Grade 1) C F Moderate (Grade 2) C F > < > > <80 Severe (Grade 3) C F >40 C >104 F >25 Intubation Potentially Life Threatening (Grade 4) ER visit or hospitalization for arrhythmia ER visit or hospitalization for arrhythmia ER visit or hospitalization for malignant hypertension ER visit or hospitalization for malignant hypertension ER visit or hospitalization for hypotensive shock

36 VS Toxicity Shift Table N (%) with No increase Increase by 1 grade Increase by 2 grades Increase by 3 grades Increase by 4 grades (only possible with Fever based on vital signs alone)

37 ADVS Design Approach: ATOXGR, BTOXGR: Assign toxicity grade AVALCAT1, BASECAT1: Categorize results into Normal, Fever, Tachycardia, Bradycardia, Hypertension (systolic), etc. Ranges for both dependent on PARAMCD SHIFT1: Assign shift as No increase, Increase by 1 grade, Increase by 2 grades, etc.

38 ADVS Design For systolic blood pressure: (row) USUBJID PARAMCD AVISIT AVAL ATOXGR AVALCAT SYSBP Baseline Normal SYSBP Week Hypertension (systolic) SYSBP Baseline Normal SYSBP Week Hypotension (systolic) (row) BASE BTOXGR BASECAT1 SHIFT1 SHIFT1N ABLFL Normal Y Normal Increase by 1 grade Normal Y Normal Increase by 3 grades 3

39 ADVS Design The shift is based on ATOXGR, BTOXGR without reference to type of toxicity Use AVALCAT1 to select type of toxicity where PARAMCD = SYSBP and SHIFT1 ne and AVALCAT1 in ( Normal, Hypertension (systolic) ); where PARAMCD = TEMP and SHIFT1 ne and AVALCAT1 in ( Normal, Fever );

40 Karen G. Malley Malley Research Programming, Inc. Tel: