Template. Every bracketed field is a decision to make and record before the analysis starts. A plan written after the modelling is not an analysis plan, and the difference is visible to a reviewer.
Study/programme: [ ] Compound: [ ] Plan version and date: [ ] Author: [ ] Reviewers: [ ]
Primary objective: [ ]
Each objective must name the decision it informs — a dose for the next study, a label statement, a covariate adjustment, a waiver. "Characterise the population pharmacokinetics" is not an objective; it is an activity.
Secondary objectives: [ ]
Intended use of the model: [ ] — regulators evaluate a model against its intended use, and the required rigour follows from it.
| Item | Specification |
|---|---|
| Studies included | [ ] |
| Analysis population | [ ] |
| Analyte and matrix | [ ] |
| Assay and LLOQ | [ ] (see the bioanalytical validation report) |
| Time reference | actual elapsed time from the most recent dose |
| Dataset specification | [ reference the document ] |
| Derivation script | [ path / repository ] |
Exclusions, defined now and applied blind to the model:
BLQ handling: [ M1 / M3 / other ]. Justification: [ ]. Expected BLQ fraction: [ ]%. If the observed BLQ fraction exceeds [ ]%, the method changes to M3.
Missing covariates: [ imputation rule, or exclusion ]. Missingness will be tabulated before imputation.
| Estimation | [ NONMEM 7.x / Monolix / nlmixr2 ] version [ ] |
| Orchestration and post-processing | [ Pharmpy / PsN / R ] version [ ] |
| Estimation method | [ FOCE-I / SAEM followed by IMP ] |
| Environment | [ container / lockfile reference ] |
Starting point: [ ] compartments, [ ] absorption, [ ] elimination.
Candidate structures to be evaluated: [ ]
Parameterisation is clearance-based (CL, V, Q, Vp) in all candidates.
Selection criteria, in this order: physiological plausibility; residual patterns; likelihood-ratio test for nested models (ΔOFV > [3.84] at 1 df); BIC; parameter precision. An extra compartment whose intercompartmental clearance has RSE above [50]% is not retained regardless of the objective function.
Candidates: [ proportional / additive / combined / log-transform-both-sides ]. Separate error models by [ study / assay / matrix ]: [ yes / no, with justification ].
Covariates included a priori on mechanistic grounds, not tested:
Covariates to be evaluated:
| Covariate | Parameter(s) | Functional form | Rationale |
|---|---|---|---|
| [ ] | [ ] | [ ] | [ ] |
Procedure: [ stepwise covariate modelling / full model estimation ]. If stepwise: forward inclusion at p < [0.05] (ΔOFV > 3.84), backward elimination at p < [0.001] (ΔOFV > 10.83). Note that stepwise selection biases effect sizes upward and narrows intervals; a full-model approach is preferred where the objective is to quantify an effect.
Clinical relevance threshold: a covariate effect is reported as relevant if it changes [ exposure metric ] by more than [ ]% across the [5th–95th] percentile of the covariate.
Acceptance criteria for the final model: [ ]
Purpose: [ ] Scenarios: [ ] Replicates: [ ] Population sampled from: [ ] Uncertainty in fixed effects propagated: [ yes / no ] Endpoint summarised: [ ]
Any departure from this plan is recorded in the report with its reason and the date it was decided. Post hoc analyses are labelled as such and reported separately from the pre-specified analysis.
Approvals
| Role | Name | Signature | Date |
|---|---|---|---|
| Author | |||
| Reviewer | |||
| Clinical pharmacology |