Protocol and Other Documents

Documents of Data Management and Statistical Activities

Design, conduction, evaluation and reporting of clinical trials are encompassed by different documentation reqirements. Some types of documents support of planning and conduction of the trial. E.g. a Data Management Plan tells the player how to manage the data (when they will be available). Or a Statistical Analysis Plan tells how to analyse and report the collected information. 

Other documents are show the outcome of the study. The tables, listing and graphs are the direct outputs of statistical evaluation. Statistical Report is a structured and commented selection of the main results. 

Between the plans and outcomes there are documents which support the working processes (delivery logs, checklists), document the activities (programming logs), serve the quality assurance (review documents) and preserve the anomalies experienced during the different steps (not-to-files). 

The primary document of the data management is the Data Management Plan (DMP). It shows all important aspect of data collection, storage or handling of exceptions. Sometimes a so called Data Validation Plan is also created. This document is about the processes to assure that the data in the clinical trial database surely be identical with the healtcare data. 

Query management is an important part of data managements. The first step to that is to set up the check list, that is the list of syntactical or semantical rules to be checked among the data. Majority of such checks can be integrated into the eCRF for data collection, but a process for manual querying should also be established. 

While all the data corrections should be performed by Investigators there might be automatic, self-evident corrections. The best example for that is to assure identical form of month (01/Jan/January/1 = January, etc.).

Coding is done by ATC or MedDRA dictionaries for the drugs and Adverse Events respectively. 

Specification of Protocol Deviations summarises and classifies the observed protocol deviation. This document and especially the classification of the events into minor and major has a decisive role in setting the analysis population flags. 

Statistical activities – not considering the statistical programming itself – can be summarised in three main documents:

  • Statistical Analysis Plan (SAP)
    • SAP contains all the relevant information to perform the statistical analysis. Namely, it very clearly associate statistical methods to analysis of primary and secondary endpoints, demographic data, laboratory observations, adverse events, etc. SAP also determines the criteria of testing procedures and the significance levels. The writers of SAPs are also SAS programmers and as such they have the responsibility to give guidance for a proper parametrisation of SAS functions. Alternative approaches of analysis should also be mentioned in the SAP: we all know that the classical ANOVA can only be done if the standard deviations of the groups are close to each other. Otherwise some non-parametric test should be applied. These choices are clearly highlighted in SAPs. 
  • Table shells
    • Table shell is the empty report containing tables, listings and graphs. Each letter (and each space) has its own importance in the reporting. The table shell for tables and listing contains all the headers, footers, titles, numbering and even some rules for the content, e.g. the number of decimal places or indication of missing values. Footnotes are also very important in interpretation of the results, they are also planned and contained in table shells. 
  • Statistical Report
    • Statistical report is a commented summary of the main results. A more deteiled description can be found here. 

This activity practically means the programming, the evaluation of the study. The work is driven by the SAP and Table Shell and supported by some specific SOPs, like application of programmic conventions in the program code development. 

As the activity is programming which can only be understood by programmers, it is very important to declare the quality assurance with introduction of several reviewers to follow and control the programming activities. The most important documents of this phase are the quality assurance documents which accompany the whole code development. 

Some unexpected situation can emerge during evaluation leading to a modification of the SAP or the Table Shell. Such actions should also be documented appropriately. 

The outcome of reporting is the Statistical Report. This activity and document is described in more details here.