{ "source": { "title": "Standard Safety Tables and Figures: Integrated Guide", "publisher": "FDA CDER, Biomedical Informatics and Regulatory Review Science (BIRRS)", "version": "2.0", "date": "2025-04", "pages": 136, "pdf": "~/Desktop/standard_safety_tables_and_figures_integrated_guide_2025.pdf", "companion_code": "NONE — the guide names no reference implementation; every display carries the placeholder footnote 'Source: [include Applicant source, datasets and/or software tools used]'", "tiers": { "core": "Section 2 — generated automatically in every ST&F package", "expanded": "Section 3 — deeper/alternate views, also generated automatically", "optional": "Section 4 — generated only on review-team request", "appendix": "Section 5 — reference criteria tables, not analysis outputs" }, "counts": { "numbered_tables": 60, "numbered_figures": 22, "diagrams": 2, "reference_tables_in_appendix": 5, "listings_among_tables": 6, "analysis_tables": 49, "unnumbered_analog_displays": "~12 (Figure 6 x4 panels, Table 20 x4 panels, Table 35 x4 panels)" } }, "figures": [ {"id": "F1", "tier": "core", "section": "2.1.7", "title": "Kaplan-Meier Plot: Time to Permanent Discontinuation of Treatment", "chart_type": "km", "domains": ["ADSL"], "notes": "at-risk + cumulative-events strip tables, log-rank, pointwise 95% CI bars"}, {"id": "F2", "tier": "core", "section": "2.2.4.1", "title": "Subjects With Adverse Events by System Organ Class", "chart_type": "dot_forest_dual", "domains": ["ADAE"], "notes": "left panel % by arm (dot), right panel risk difference w/ 95% CI (forest); sorted by risk difference; ~24 SOCs"}, {"id": "F3", "tier": "core", "section": "2.2.4.4", "title": "Subjects With Adverse Events >=X% in Any Treatment Arm by OCMQ (Narrow)", "chart_type": "dot_forest_dual", "domains": ["ADAE"], "notes": "same dual-panel as F2 at OCMQ level; ~55 terms"}, {"id": "F4", "tier": "core", "section": "2.2.5.2", "title": "Kaplan-Meier Plot: Time to Onset of [AE of Interest]", "chart_type": "km", "domains": ["ADAE"], "notes": "cumulative incidence; not informative if N<8 per arm; one per AE of interest"}, {"id": "F5", "tier": "core", "section": "2.4.1.1", "title": "Proportion of Subjects Remaining in Trial at Each Visit by Availability of [Lab Value] Result", "chart_type": "bar_paired", "domains": ["ADLB"], "notes": "solid bar = has result, open bar = missing, height = % remaining; x = discrete visit"}, {"id": "F6", "tier": "core", "section": "2.4.2", "title": "Mean General Chemistry Data Change From Baseline Over Time by Treatment Arm", "chart_type": "line_ci", "domains": ["ADLB"], "analogs": ["Kidney Function", "Liver Biochemistry", "Lipids", "Hematology"], "notes": "mean change + 95% CI error bars by visit/arm; extreme values excluded; <10%-data visits dropped"}, {"id": "F7", "tier": "core", "section": "2.4.4.2", "title": "Hepatocellular Drug-Induced Liver Injury Screening Plot", "chart_type": "scatter_quadrant", "domains": ["ADLB"], "notes": "eDISH: x = max ALT/AST xULN, y = max TB xULN; quadrants Potential Hy's Law / Cholestasis / Temple's Corollary; 30-day pairing window", "safetyviz_equivalent": "hep-explorer (eDISH)"}, {"id": "F8", "tier": "core", "section": "2.4.4.3", "title": "Cholestatic Drug-Induced Liver Injury Screening Plot", "chart_type": "scatter_quadrant", "domains": ["ADLB"], "notes": "x = max ALP xULN, y = max TB xULN; 2xULN/2xULN cutoffs", "safetyviz_equivalent": "hep-explorer variant"}, {"id": "F9", "tier": "core", "section": "2.5.1", "title": "Mean Vital Sign Data Change From Baseline Over Time by Treatment Arm", "chart_type": "line_ci", "domains": ["ADVS"], "notes": "same design as F6; SBP, DBP, HR, RR, temperature"}, {"id": "F10", "tier": "core", "section": "2.5.2.1", "title": "Box Plot: Median and Interquartile Range of Vital Sign Data Over Time by Treatment Arm", "chart_type": "boxplot_time", "domains": ["ADVS"], "notes": "box = IQR, whiskers = 1.5xIQR, outlier points; mean + n tables below"}, {"id": "F11", "tier": "core", "section": "2.6.3.1", "title": "Kaplan-Meier Plot: Cumulative Incidence of [AE] Over Time With Pointwise 95% Confidence Interval (OLE)", "chart_type": "km", "domains": ["ADAE", "ADSL"], "notes": "drug curve continues through OLE; control truncates at end of randomized period"}, {"id": "F12", "tier": "core", "section": "2.6.3.2", "title": "Rate of [AE] Over Time (OLE)", "chart_type": "pointrange", "domains": ["ADAE"], "notes": "incidence rate per 100 PY with 95% CI over discrete intervals (0-12, 12-24, ... >48 wk)"}, {"id": "F13", "tier": "expanded", "section": "3.1.1", "title": "Kaplan-Meier Plot: Time to Last Follow-Up", "chart_type": "km", "domains": ["ADSL"], "notes": "loss-to-follow-up tracking; x in years"}, {"id": "F14", "tier": "optional", "section": "4.1.1.1", "title": "Kaplan-Meier Plot: Time to Onset of [AE]", "chart_type": "km", "domains": ["ADAE"], "notes": "generalization of F4 to any AE/SAE on request"}, {"id": "F15", "tier": "optional", "section": "4.3.1.1", "title": "Baseline vs. Maximum/Minimum Postbaseline [Lab Value] by Treatment Arm", "chart_type": "shift_scatter", "domains": ["ADLB"], "notes": "scatter + per-arm linear regression + no-change diagonal; separate figure for min", "safetyviz_equivalent": "shift-plot (P004 renderer #2)"}, {"id": "F16", "tier": "optional", "section": "4.3.3.1", "title": "Median and Interquartile Range for General Chemistry Data Over Time by Treatment Arm", "chart_type": "boxplot_time", "domains": ["ADLB"]}, {"id": "F17", "tier": "optional", "section": "4.3.3.2", "title": "Median and Interquartile Range for Kidney Function Data Over Time by Treatment Arm", "chart_type": "boxplot_time", "domains": ["ADLB"]}, {"id": "F18", "tier": "optional", "section": "4.3.3.3", "title": "Median and Interquartile Range for Liver Biochemistry Data Over Time by Treatment Arm", "chart_type": "boxplot_time", "domains": ["ADLB"]}, {"id": "F19", "tier": "optional", "section": "4.3.3.4", "title": "Median and Interquartile Range for Lipid Data Over Time by Treatment Arm", "chart_type": "boxplot_time", "domains": ["ADLB"]}, {"id": "F20", "tier": "optional", "section": "4.3.3.5", "title": "Median and Interquartile Range for Hematology Data Over Time by Treatment Arm", "chart_type": "boxplot_time", "domains": ["ADLB"]}, {"id": "F21", "tier": "optional", "section": "4.4.1.1", "title": "Proportion of Subjects Remaining in Trial at Each Visit by Availability of [Vital Sign] Result", "chart_type": "bar_paired", "domains": ["ADVS"], "notes": "vital-sign twin of F5"}, {"id": "F22", "tier": "optional", "section": "4.4.2.1", "title": "Baseline vs. Maximum/Minimum Postbaseline [Vital Sign] by Treatment Arm", "chart_type": "shift_scatter", "domains": ["ADVS"], "notes": "vital-sign twin of F15"} ], "chart_type_rollup": { "km": ["F1", "F4", "F11", "F13", "F14"], "dot_forest_dual": ["F2", "F3"], "boxplot_time": ["F10", "F16", "F17", "F18", "F19", "F20"], "line_ci": ["F6", "F9"], "scatter_quadrant": ["F7", "F8"], "shift_scatter": ["F15", "F22"], "bar_paired": ["F5", "F21"], "pointrange": ["F12"], "distinct_chart_engines_required": 8, "note": "22 numbered figures collapse to 8 reusable chart engines; parameterization (analyte, panel, population) generates the rest" }, "tables": [ {"id": "T1", "tier": "core", "section": "2.1.1", "type": "table", "title": "Clinical Trials Submitted in Support of Efficacy and Safety Determinations for [Drug]", "domains": ["trial metadata"]}, {"id": "T2", "tier": "core", "section": "2.1.2", "type": "table", "title": "Demographics and Baseline Clinical Characteristics", "domains": ["ADSL"]}, {"id": "T3", "tier": "core", "section": "2.1.3", "type": "table", "title": "Subject Screening and Enrollment", "domains": ["ADSL"]}, {"id": "T4", "tier": "core", "section": "2.1.4", "type": "table", "title": "Subject Populations", "domains": ["ADSL"]}, {"id": "T5", "tier": "core", "section": "2.1.5", "type": "table", "title": "Discontinuation of Treatment or Trial Participation", "domains": ["ADSL"]}, {"id": "T6", "tier": "core", "section": "2.1.6", "type": "table", "title": "Duration of Treatment Exposure", "domains": ["ADSL", "ADEX"]}, {"id": "T7", "tier": "core", "section": "2.2.1", "type": "table", "title": "Overview of Adverse Events", "domains": ["ADAE"], "stats": "n (%), risk difference % (95% CI)"}, {"id": "T8", "tier": "core", "section": "2.2.2.1", "type": "table", "title": "Deaths", "domains": ["ADAE", "ADSL"]}, {"id": "T9", "tier": "core", "section": "2.2.2.2", "type": "listing", "title": "All Individual Subject Deaths", "domains": ["ADAE", "ADSL"]}, {"id": "T10", "tier": "core", "section": "2.2.2.3", "type": "table", "title": "Subjects With Serious Adverse Events by System Organ Class and Preferred Term", "domains": ["ADAE"]}, {"id": "T11", "tier": "core", "section": "2.2.2.4", "type": "table", "title": "Subjects With Serious Adverse Events by Organ System and OCMQ (Narrow)", "domains": ["ADAE"]}, {"id": "T12", "tier": "core", "section": "2.2.3.1", "type": "table", "title": "Subjects With Adverse Events Leading to Treatment Discontinuation by SOC and Preferred Term", "domains": ["ADAE"]}, {"id": "T13", "tier": "core", "section": "2.2.3.2", "type": "table", "title": "Subjects With Adverse Events Leading to Treatment Discontinuation by Organ System and OCMQ (Narrow)", "domains": ["ADAE"]}, {"id": "T14", "tier": "core", "section": "2.2.4.2", "type": "table", "title": "Subjects With Adverse Events by System Organ Class and Preferred Term", "domains": ["ADAE"]}, {"id": "T15", "tier": "core", "section": "2.2.4.3", "type": "table", "title": "Subjects With Common Adverse Events Occurring at >=X% Frequency by Preferred Term", "domains": ["ADAE"]}, {"id": "T16", "tier": "core", "section": "2.2.4.3", "type": "table", "title": "Incidence Rate Analysis", "domains": ["ADAE"], "stats": "IR per 100 person-years, incidence rate difference (95% CI)"}, {"id": "T17", "tier": "core", "section": "2.2.4.5", "type": "table", "title": "Subjects With Adverse Events by Organ System and OCMQ", "domains": ["ADAE"], "notes": "side-by-side Narrow | Broad column blocks"}, {"id": "T18", "tier": "core", "section": "2.2.5.1", "type": "table", "title": "Summary Assessment of [AE of Interest]", "domains": ["ADAE"]}, {"id": "T19", "tier": "core", "section": "2.3.1", "type": "table", "title": "Subjects With [OCMQ/AE of Interest] by Demographic Subgroups", "domains": ["ADAE", "ADSL"], "notes": "FDASIA Section 907 subgroup reporting"}, {"id": "T20", "tier": "core", "section": "2.4.3", "type": "table", "title": "Subjects With Kidney Function Analyte Values Exceeding Specified Levels", "domains": ["ADLB"], "analogs": ["General Chemistry", "Liver Biochemistry", "Lipids", "Hematology"]}, {"id": "T21", "tier": "core", "section": "2.4.4.4.1", "type": "table", "title": "Subjects in Quadrant of Interest for Potential Hepatocellular DILI Screening Plot", "domains": ["ADLB"], "notes": "companion counts for F7"}, {"id": "T22", "tier": "core", "section": "2.4.4.4.1", "type": "table", "title": "Subjects in Quadrants of Interest for Potential Cholestatic DILI Screening Plot", "domains": ["ADLB"], "notes": "companion counts for F8"}, {"id": "T23", "tier": "core", "section": "2.6.2.1.1", "type": "table", "title": "Subjects Receiving Study Drug With Potential Adverse Reactions Identified by the Review Team by SOC and PT (OLE)", "domains": ["ADAE"]}, {"id": "T24", "tier": "core", "section": "2.6.2.2.1", "type": "table", "title": "OLE Approach 1 — Only OLE Data From Subjects Randomized to Drug", "domains": ["ADAE"]}, {"id": "T25", "tier": "core", "section": "2.6.2.2.2", "type": "table", "title": "OLE Approach 2 — All Data From At-Risk Time on Drug", "domains": ["ADAE"]}, {"id": "T26", "tier": "core", "section": "2.6.4.1", "type": "table", "title": "Common AEs With Incidence Rate >=X by SOC and PT (OLE)", "domains": ["ADAE"]}, {"id": "T27", "tier": "core", "section": "2.6.4.2", "type": "table", "title": "Common AEs With IR >=X (Only OLE Data)", "domains": ["ADAE"]}, {"id": "T28", "tier": "core", "section": "2.6.4.3", "type": "table", "title": "Common AEs With IR >=X (All Data From At-Risk Time)", "domains": ["ADAE"]}, {"id": "T29", "tier": "expanded", "section": "3.2.1", "type": "table", "title": "Subjects With SAEs by Organ System, OCMQ (Narrow) and Preferred Term", "domains": ["ADAE"]}, {"id": "T30", "tier": "expanded", "section": "3.2.2", "type": "table", "title": "Subjects With AEs Leading to Treatment Discontinuation by Organ System, OCMQ (Narrow) and PT", "domains": ["ADAE"]}, {"id": "T31", "tier": "expanded", "section": "3.2.3", "type": "table", "title": "Subjects With AEs by Organ System, OCMQ (Narrow) and Preferred Term", "domains": ["ADAE"]}, {"id": "T32", "tier": "expanded", "section": "3.2.3", "type": "table", "title": "Subjects With AEs by SOC, Preferred Terms NOT Captured in OCMQs (Narrow)", "domains": ["ADAE"]}, {"id": "T33", "tier": "expanded", "section": "3.2.3", "type": "table", "title": "Subjects With AEs by Male-Specific OCMQ (Narrow) and PT", "domains": ["ADAE", "ADSL"]}, {"id": "T34", "tier": "expanded", "section": "3.2.3", "type": "table", "title": "Subjects With AEs by Female-Specific OCMQ (Narrow) and PT", "domains": ["ADAE", "ADSL"]}, {"id": "T35", "tier": "expanded", "section": "3.3.1", "type": "table", "title": "Mean Change From Baseline for Kidney Function Data Over Time by Treatment Arm", "domains": ["ADLB"], "analogs": ["General Chemistry", "Liver Biochemistry", "Lipids", "Hematology"], "notes": "numeric backing for F6"}, {"id": "T36", "tier": "expanded", "section": "3.4.1", "type": "table", "title": "Subjects With Maximum Postbaseline Systolic Blood Pressure by Category", "domains": ["ADVS"]}, {"id": "T37", "tier": "expanded", "section": "3.4.1", "type": "table", "title": "Subjects With Maximum Postbaseline Diastolic Blood Pressure by Category", "domains": ["ADVS"]}, {"id": "T38", "tier": "expanded", "section": "3.4.1", "type": "table", "title": "Subjects Meeting Specific Postbaseline Hypotension Levels", "domains": ["ADVS"]}, {"id": "T39", "tier": "optional", "section": "4.1.2", "type": "listing", "title": "Listing of Subjects With Adverse Events Leading to Treatment Discontinuation", "domains": ["ADAE"]}, {"id": "T40", "tier": "optional", "section": "4.1.3.1", "type": "table", "title": "Adverse Events Occurring at >=X% in Drug-Treated Group and >=Y% More Than Control", "domains": ["ADAE"], "notes": "starting point for USPI labeling Section 6.1"}, {"id": "T41", "tier": "optional", "section": "4.1.3.2", "type": "listing", "title": "Listing of Subjects With Select Narrow OCMQs", "domains": ["ADAE"]}, {"id": "T42", "tier": "optional", "section": "4.1.3.3", "type": "listing", "title": "Listing of Subjects With Select Broad OCMQs", "domains": ["ADAE"]}, {"id": "T43", "tier": "optional", "section": "4.1.3.4", "type": "table", "title": "Subjects With AEs by Organ System, OCMQ (Broad) and Preferred Term", "domains": ["ADAE"]}, {"id": "T44", "tier": "optional", "section": "4.1.3.5", "type": "table", "title": "Subjects With AEs by Male-Specific OCMQ (Broad) and PT", "domains": ["ADAE", "ADSL"]}, {"id": "T45", "tier": "optional", "section": "4.1.3.5", "type": "table", "title": "Subjects With AEs by Female-Specific OCMQ (Broad) and PT", "domains": ["ADAE", "ADSL"]}, {"id": "T46", "tier": "optional", "section": "4.1.3.6", "type": "table", "title": "Subjects With Muscle Injury Algorithmic OCMQ", "domains": ["ADAE", "ADLB"], "notes": "algorithmic: AE terms + CPK/myoglobin within 7-day window"}, {"id": "T47", "tier": "optional", "section": "4.1.3.7", "type": "table", "title": "Subjects With Hypoglycemia Algorithmic OCMQ", "domains": ["ADAE", "ADLB", "ADMH"], "notes": "3 population panels by diabetes history"}, {"id": "T48", "tier": "optional", "section": "4.1.3.8", "type": "table", "title": "Subjects With Hyperglycemia Algorithmic OCMQ", "domains": ["ADAE", "ADLB", "ADCM", "ADMH"]}, {"id": "T49", "tier": "optional", "section": "4.1.3.9", "type": "table", "title": "Subjects With Hypersensitivity Algorithmic OCMQ", "domains": ["ADAE"], "notes": "modeled on MedDRA anaphylaxis algorithmic SMQ"}, {"id": "T50", "tier": "optional", "section": "4.2.1.1", "type": "table", "title": "Overview of Serious Adverse Events by Demographic Subgroup", "domains": ["ADAE", "ADSL"]}, {"id": "T51", "tier": "optional", "section": "4.2.1.1", "type": "table", "title": "Overview of Adverse Events by Demographic Subgroup", "domains": ["ADAE", "ADSL"]}, {"id": "T52", "tier": "optional", "section": "4.3.2.1", "type": "table", "title": "Subjects With Last On-Treatment Chemistry Value >= Level 2 Criteria", "domains": ["ADLB"]}, {"id": "T53", "tier": "optional", "section": "4.3.2.2", "type": "table", "title": "Subjects With Last On-Treatment Hematology Value >= Level 2 Criteria", "domains": ["ADLB"]}, {"id": "T54", "tier": "optional", "section": "4.3.3.6", "type": "listing", "title": "Listing of Subjects With a Laboratory Value >= Level 2 Criteria", "domains": ["ADLB"]}, {"id": "T55", "tier": "optional", "section": "4.3.3.7", "type": "listing", "title": "Listing of Subjects With a Laboratory Value >= Level 2 Change From Baseline Criteria", "domains": ["ADLB"]}, {"id": "T56", "tier": "appendix", "section": "5.1.1", "type": "reference", "title": "Abnormality Level Criteria for Chemistry Laboratory Results", "notes": "Level 1/2/3 thresholds — a DATA ASSET, not a display"}, {"id": "T57", "tier": "appendix", "section": "5.1.2", "type": "reference", "title": "Abnormality Level Criteria for Hematology Laboratory Results", "notes": "Level 1/2/3 thresholds — a DATA ASSET, not a display"}, {"id": "T58", "tier": "appendix", "section": "5.2.1", "type": "reference", "title": "Extreme Chemistry Values Suggestive of Laboratory Error (v1.0)", "notes": "US + SI thresholds; drives extreme-value exclusion rule"}, {"id": "T59", "tier": "appendix", "section": "5.2.2", "type": "reference", "title": "Extreme Hematology Values Suggestive of Laboratory Error (v1.0)"}, {"id": "T60", "tier": "appendix", "section": "5.2.3", "type": "reference", "title": "Extreme Vital Sign Values Suggestive of Error (v1.0)"} ], "cross_cutting_rules": [ "Title suffix convention: every display ends '..., Safety Population, Pooled Analysis (or Trial X)'", "Every display carries: Source footnote, TEAE-definition + MedDRA-version note, Duration note, alphabetized Abbreviations line", "Risk Difference % (95% CI) is the standard treatment-effect statistic; NOT multiplicity-adjusted; descriptive/signal-detection only", "Default ordering is by decreasing risk difference, not alphabetical", "Populations: ITT, mITT, Safety (>=1 dose), Per-protocol; Safety is default for AE/lab/VS displays", "OCMQ (OND Custom Medical Query, formerly FMQ): Narrow = default, Broad = on request; broad subsumes narrow; never sum narrow+broad (double counting)", "Each OCMQ maps to exactly one organ system by clinical judgment even when it spans MedDRA SOCs", "Extreme-value exclusion: values beyond Tables 58/59/60 thresholds removed from mean-change displays as likely lab error", "Sparse-data rule: visits with data from <10% of subjects in all arms excluded from change-over-time displays", "Unscheduled visits mapped to nearest protocol-specified visit; approach stated in footnote", "Sex-specific displays restrict the denominator (Ns) to that sex", "KM convention: at-risk + cumulative-event strip tables beneath every KM plot, log-rank, pointwise 95% CI bars, earliest qualifying event = event time", "Box plot convention: box = IQR, line = median, whiskers = 1.5xIQR, points beyond = outliers; mean + n tables beneath", "Shift plot convention: gray dotted diagonal = no change, solid line = drug-arm regression, gray dashed = control-arm regression", "DILI plot convention: quadrant cutoffs TB 2xULN with ALT/AST 3xULN (hepatocellular) or ALP 2xULN (cholestatic), 30-day default pairing window", "Established grading systems (DAIDS for HIV, CTCAE for oncology) may substitute for Table 56/57 criteria", "Separate ST&F packages per registration trial or per substantially different trial design" ] }