There is a considerable body of literature explaining statistical methods for observational studies but very little addressing the statistical analysis plan. A clear guide to general principles and the need for a plan is given in Design of Observational Studies (P.R. Rosenbaum, Springer Series in Statistics, 2010. Chapter 18), which also gives useful advice on how to test complex hypotheses in a way that minimizes the chances of drawing incorrect conclusions.
Planning analyses for randomised clinical trials is covered in a number of publications. These often give checklists of the component parts of an analysis plan and much of this applies equally to non-randomised designs. A good reference in this respect is the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). ICH E9 ‘Statistical Principles for Clinical Trials’. While specific guidance on the statistical analysis plan for epidemiological studies is sparse, the following principles will apply to most of the studies.
Pre-specification of statistical and epidemiological analyses can be challenging for data that are not collected specifically to answer the study questions. This is often the case in observational studies, where secondary data are used. However, thoughtful specification of the way missing values will be handled or the use of a small part of the data as a pilot set to guide analysis can be useful techniques to overcome such problems. A feature common to most studies is that some not pre-specified analyses will be performed in response to observations in the data to help interpretation of results. It is important to distinguish between such data-driven analyses and the pre-specified findings. Post-hoc modifications to the analysis strategy should be noted and explained. The statistical analysis plan provides a confirmation of this process.
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 studies are to be performed to inform the design phase. Feasibility studies should be independent of the main study results.