A case definition compatible with the observational database should be developed for each outcome of a study at the design stage. This description should include how events will be identified and classified as cases, whether cases will include prevalent as well as incident cases, exacerbations and second episodes (as differentiated from repeat codes) and all other inclusion or exclusion criteria. The reason for the data collection and the nature of the healthcare system that generated the data should also be described as they can impact on the quality of the available information and the presence of potential biases. Published case definitions of outcomes, such as those developed by the Brighton Collaboration in the context of vaccinations, are not necessarily compatible with the information available in a given observational data set. For example, information on the duration of symptoms may not be available, or additional codes may have been added to the data set following publication of the outcome definition.
Search criteria to identify outcomes should be defined and the list of codes should be provided. Generation of code lists requires expertise in both the coding system and the disease area. Researchers should also consult clinicians who are familiar with the coding practice within the studied field. Suggested methodologies are available for some coding systems (see Creating medical and drug code lists to identify cases in primary care databases. Pharmacoepidemiol Drug Saf 2009;18(8):704-7). Coding systems used in some commonly used databases are updated regularly so sustainability issues in prospective studies should be addressed at the protocol stage. Moreover, great care should be given when re-using a code list from another study as code lists depend on the study objective and methods. Public repository of codes as Clinicalcodes.org is available and researchers are also encouraged to make their own set of coding available.
In some circumstances, chart review or text entries in electronic format linked to coded entries can be useful for outcome identification. Such identification may involve an algorithm with use of multiple code lists (for example disease plus therapy codes) or an endpoint committee to adjudicate available information against a case definition. In some cases, initial plausibility checks or subsequent medical chart review will be necessary. When databases have prescription data only, drug exposure may be used as a proxy for an outcome, or linkage to different databases is required.
|10. Specific topics|
|Annex 1.||Guidance on conducting systematic revies and meta-analyses of completed comparative pharmacoepidemiological studies of safety outcomes|