ENCePP Guide on Methodological Standards in Pharmacoepidemiology

12.2. Timing of the statistical analysis plan

The SAP is crucial for guiding data analysis and therefore, it is useful to formulate it at an early stage. In particular, the SAP should be developed before any informal inspection of aspects of the data or results that might influence opinions regarding the study hypotheses. Ideally, the SAP will be developed as soon as the protocol is finalised.

The SAP may be submitted to regulatory authorities as part of a submission package, e.g., as an appendix to the protocol and/or study report. The SAP is stored in the study master file, and is used during audits to check if statistical analyses are performed as planned. The role of the SAP is explained in the International Council for Harmonisation (ICH) E9 guideline 'Statistical principles for clinical trials, and these recommendations may also apply to observational studies.

A particular concern in retrospective studies is that decisions about the analysis should be made blinded to any knowledge of the results. This should be a consideration in the study design, particularly when feasibility assessments are to be performed to inform the design phase. Such feasibility assessments should be independent of the study results (see Chapter 2).

At any cost, a SAP should always be completed before the data have been unblinded for the statistician. This contributes to transparency of the study process and confirms that the set of analyses have not been influenced by the data. Making alterations to a planned statistical analysis after seeing the data increases the risk of bias, inflates the probability of type I errors, and might jeopardise the validity of the study findings, and acceptance of the study.

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