Crossover bioequivalence
Set up, run, and review this analysis in Lifescio.
Supported analysis
Use two periods and two sequences: reference then test, or test then reference. The app models log exposure with treatment, period and subject effects, exponentiates the treatment contrast and constructs a 90% interval with two one-sided tests.
Supported scope: This implementation requires balanced, complete 2×2 crossover data, no carryover and a common residual variance. Replicate designs, reference-scaled limits and missing periods are not supported. The linked M13A guidance has a specific dosage-form scope.
Prepare data and configure the analysis
Enter numeric Subject, Sequence, Period, Treatment, and positive Exposure. Treatment 0 is reference and 1 is test. Sequence 0 is reference then test; sequence 1 is test then reference. Periods are 1 and 2. Every subject needs both periods in one fixed sequence.
The supported design is a balanced 2×2 crossover with at least three subjects in each sequence. Enter lower and upper ratio limits bracketing one, such as 0.80 and 1.25 when appropriate to the study. Supply raw positive exposure; the engine performs the logarithm.
Input reference (3 fields)
Enter your data and prespecified choices. Ranges include both limits. For table fields, use cell editing, Paste data, or Import CSV / TSV. Review whether the first imported row contains headings and map the source columns before applying the import. Empty numeric cells are not treated as zero. Open file is for an exported Lifescio analysis JSON file, not a spreadsheet.
| Input | Format | Allowed range | Guidance |
|---|---|---|---|
| Crossover observations | Table | — | Sequence 0: reference then test; sequence 1: test then reference. Treatment 0 reference, 1 test. Columns in order: Subject; Sequence; Period; Treatment; Exposure. |
| Lower ratio limit | Number | 0.1–1 | — |
| Upper ratio limit | Number | 1–10 | — |
Run and review
- Give the analysis a descriptive name and review every example value. Record units, data preparation, and planning assumptions in Reproducibility & notes. For simulations, record the seed and replication or sampling settings.
- Choose Run analysis. Resolve input errors before interpreting output. In the connected app, a run uses a saved input revision; local preview runs need the page to stay open.
- Review Diagnostics for method limitations, warnings, and available numerical checks. A completed run means computation finished; it does not establish that the assumptions fit your study.
- Use the Result table selector to inspect each output. Editing inputs does not recalculate existing results: an earlier-input notice means you need to run again to obtain matching results.
Understand the outputs
Bioequivalence shows the test/reference geometric mean ratio, 90% limits, lower and upper one-sided test p-values, and whether the interval is within the entered limits. The Within limits decision uses unrounded values, so rounded endpoint displays can conceal a marginal failure.
Model diagnostics contains residual degrees of freedom, residual log standard deviation, and within-subject coefficient of variation in percent. The fit includes subject and period effects. It does not evaluate all product-specific regulatory requirements.
Troubleshooting and common mistakes
For a sequence error, check treatment codes against period and assigned sequence. For imbalance or missing-period errors, use an analysis that supports the actual design; do not fabricate rows or selectively remove participants to force balance.
Zero exposure cannot be logged. Below-quantification handling must be justified before import. Replicate designs, reference-scaled limits, and carryover models are outside this workflow. A nonsignificant treatment difference is not a substitute for the displayed equivalence decision.
After correcting inputs, run again and check that the results belong to the new input snapshot. Increasing simulation draws improves numerical precision only; it does not repair invalid data or an unsuitable model.
Save, compare, and export
In the connected app, Save analysis retains the inputs in your account. Run history lets you inspect earlier runs, each with the input revision it used. In local preview, Save analysis downloads an input file instead; download results before leaving the page.
Use Result + inputs for a JSON archive containing the completed result and its inputs, Download CSV for the selected result table, PDF report for a report, and a chart's SVG button for its figure. Table displays round to three decimals; CSV and JSON exports retain calculation precision. Use those values when assessing a result near a decision boundary.
To reopen an archive, select the matching analysis method and choose Open file. Imported inputs start a new draft; a result archive can also display its retained result. It does not attach itself to an existing account analysis or recompute the result. Save or run the imported draft when you want a new account record.