This section concerning documentation of operational aspects of clinical trial statistical activities should be read in conjunction with ICH E9 Statistical Principles for Clinical Trials and ICH E9(R1) Addendum on Estimands and Sensitivity Analysis in Clinical Trials to The Guideline on Statistical Principles for Clinical Trials, which provides detailed guidance on statistical principles for clinical development, trial design, conduct, analysis and reporting.
(a) The sponsor should develop a statistical analysis plan that is consistent with the trial protocol and that details the approach to data analysis, unless the approach to data analysis is sufficiently described in the protocol.
(b) The sponsor should ensure that appropriate and documented quality control of statistical programming and data analysis is implemented (e.g., for sample size calculations, analysis results for IDMC review, outputs for clinical trial report, statistical or centralised monitoring).
(c) The sponsor should ensure the traceability of data transformations and derivations during data processing and analysis.
(d) The sponsor should ensure that the criteria for inclusion or exclusion of trial participants from any analysis set is pre-defined (e.g., in the protocol or the statistical analysis plan). The rationale for exclusion for any participant (or particular data point) should be clearly described and documented.
(e) Deviations from the planned statistical analysis or changes made to the data after the trial has been unblinded (where applicable) should be clearly documented and justified and should only occur in exceptional circumstances (e.g., data discrepancies that must
be resolved for the reliability of the trial results). Such data changes should be authorised by the investigator and reflected in an audit trail. Post-unblinding data changes and deviations from the planned statistical analyses should be reported in the clinical trial report.
(f) The sponsor should retain the statistical programming records that relate to the output contained or used in reports of the trial results, including quality control/validation activities performed. Outputs should be traceable to the statistical software programs, dated and time stamped, protected against any changes, and have access controls implemented to avoid inappropriate viewing of information that may introduce bias.