Stage 2: statistical analysis plan
Mock shells for the planned outputs
Synthetic data only: simulated for this worked example; not real trial data and not a regulatory deliverable.
Planned layouts with placeholders (x). Titles, populations and footnotes match the executed outputs in the analysis stage. Every output carries the footnote: "Synthetic data; not a regulatory deliverable."
Table 14.1.2: Demographic and Baseline Characteristics
Safety set
| Characteristic | TR (N=xx) | RT (N=xx) | Total (N=xx) |
|---|---|---|---|
| Age (years) | |||
| n | xx | xx | xx |
| Mean (SD) | xx.x (xx.x) | xx.x (xx.x) | xx.x (xx.x) |
| Median | xx.x | xx.x | xx.x |
| Min - Max | xx.x - xx.x | xx.x - xx.x | xx.x - xx.x |
| Height (cm), Weight (kg), BMI (kg/m2) | |||
| (n, Mean (SD), Median, Min - Max as for age) | |||
| Sex, n (%) | |||
| n | xx | xx | xx |
| Female | xx (xx.x%) | xx (xx.x%) | xx (xx.x%) |
| Male | xx (xx.x%) | xx (xx.x%) | xx (xx.x%) |
| Race, n (%) | |||
| n | xx | xx | xx |
| <category> | xx (xx.x%) | xx (xx.x%) | xx (xx.x%) |
| Ethnicity, n (%) | |||
| n | xx | xx | xx |
| <category> | xx (xx.x%) | xx (xx.x%) | xx (xx.x%) |
Percentages use the number of participants in the column.
Table 14.3.1.1: Overview of Treatment-Emergent Adverse Events
Safety set
| Category | Test (N=xx) | Reference (N=xx) |
|---|---|---|
| Participants with at least one TEAE | xx (xx.x%) | xx (xx.x%) |
| Total number of TEAEs | xx | xx |
| Participants with a related TEAE | xx (xx.x%) | xx (xx.x%) |
| Participants with a severe TEAE | xx (xx.x%) | xx (xx.x%) |
| Participants with a serious TEAE | xx (xx.x%) | xx (xx.x%) |
| Participants with a TEAE leading to withdrawal | xx (xx.x%) | xx (xx.x%) |
| Participants with a TEAE leading to death | xx (xx.x%) | xx (xx.x%) |
Counted by treatment at onset; each participant counts once per row; N = participants dosed with that treatment. No total column: in a crossover a participant contributes to both columns. MedDRA v28.1 (synthetic coding).
Table 14.4.1.1: Summary of Plasma SIMDRUG Concentrations (ng/mL) by Nominal Time
PK concentration set
| Nominal time (h) | Statistic | Test (N=xx) | Reference (N=xx) |
|---|---|---|---|
| 0 (pre-dose) | n (n BLQ) | xx (xx) | xx (xx) |
| Mean (SD) | xx.xx (xx.xx) | xx.xx (xx.xx) | |
| CV% | xx.x | xx.x | |
| Median | xx.xx | xx.xx | |
| Min - Max | xx.xx - xx.xx | xx.xx - xx.xx | |
| 0.25 ... 48 | (as above) | ||
BLQ (below 0.50 ng/mL) set to 0 (ICH M13A); n BLQ in parentheses. Periods excluded under the SAP rules are not summarized.
Table 14.4.4.1: Summary of Plasma SIMDRUG PK Parameters
PK parameter set
| Parameter | Statistic | Test (N=xx) | Reference (N=xx) |
|---|---|---|---|
| Cmax (ng/mL) | n | xx | xx |
| Mean (SD) | xx.x (xx.x) | xx.x (xx.x) | |
| CV% | xx.x | xx.x | |
| Geometric mean | xx.x | xx.x | |
| Geometric CV% | xx.x | xx.x | |
| Median | xx.x | xx.x | |
| Min - Max | xx.x - xx.x | xx.x - xx.x | |
| AUC(0-t), AUC(0-inf), AUC(0-inf) extrapolated (%), t1/2 (h), lambda z (1/h) | (as Cmax) | ||
| tmax (h) | n | xx | xx |
| Median | x.xx | x.xx | |
| Min - Max | x.xx - x.xx | x.xx - x.xx |
Actual sampling times. AUC by linear-up/log-down. Geometric CV% = 100*sqrt(exp(s^2) - 1). Periods excluded under the SAP rules are not summarized. AUC(0-inf) is not summarized when more than 20% is extrapolated; lambda z-based parameters are not summarized when the adjusted R-squared is below 0.90 (n excluded given in a footnote).
Table 14.4.3.1: Bioequivalence Analysis: Ratio of Geometric Means (Test/Reference) and 90% CI
Bioequivalence set
| Parameter | n | Adjusted geometric mean, Test | Adjusted geometric mean, Reference | Ratio T/R (%) | 90% CI (%) | Within-participant CV% | Within 80.00 to 125.00% |
|---|---|---|---|---|---|---|---|
| Cmax (ng/mL) | xx | xxx.x | xxx.x | xxx.xx | xx.xx, xxx.xx | xx.x | Yes/No |
| AUC(0-t) (h*ng/mL) | xx | xxx.x | xxx.x | xxx.xx | xx.xx, xxx.xx | xx.x | Yes/No |
| AUC(0-inf) (h*ng/mL), supportive | xx | xxx.x | xxx.x | xxx.xx | xx.xx, xxx.xx | xx.x | Yes/No |
GLM on ln(parameter): sequence, participant(sequence), period, formulation. Decision on unrounded limits. AUC(0-inf): participants whose AUC(0-inf) passes the parameter rules in both periods.
Table 14.4.3.2: ANOVA Effects for ln(Cmax) and ln(AUC(0-t))
Bioequivalence set
| Parameter | Effect | DF | Sum of squares | Mean square | F | Error term | p-value |
|---|---|---|---|---|---|---|---|
| Cmax / AUC(0-t) | Sequence | xx | x.xxxx | x.xxxx | xx.xx | Participant(sequence) | x.xxxx |
| Cmax / AUC(0-t) | Participant(sequence) | xx | x.xxxx | x.xxxx | xx.xx | Residual | x.xxxx |
| Cmax / AUC(0-t) | Period | xx | x.xxxx | x.xxxx | xx.xx | Residual | x.xxxx |
| Cmax / AUC(0-t) | Formulation | xx | x.xxxx | x.xxxx | xx.xx | Residual | x.xxxx |
| Cmax / AUC(0-t) | Residual | xx | x.xxxx | x.xxxx |
Sequence tested against participant(sequence); other effects against the residual. No carry-over test (ICH M13A).