ICH E3 is a guidance, not a set of rigid requirements or a template, and flexibility is inherent in its use. “The [guidance] is intended to assist sponsors in the development of a report that is complete, free from ambiguity, well organized, and easy to review.” Modifications and adaptations to the structure presented in the guidance that lead to better display and communication of information are encouraged. The introduction to ICH E3 (page 3) clearly indicates that ICH E3 is to be interpreted as a guidance, not a set of requirements: “Each report should consider all of the topics described (unless clearly not relevant) although the specific sequence and grouping of topics may be changed if alternatives are more logical for a particular study. Some data in the appendices are specific requirements of individual regulatory authorities and should be submitted as appropriate. The numbering should then be adapted accordingly.” To illustrate this flexibility, consider demographic baseline information. ICH E3 suggests presentation of this information in the efficacy evaluation, but many variations of this presentation are possible. For example, if the efficacy and safety populations differ substantially, it would be appropriate to present demographic and baseline characteristics for the safety and efficacy populations in the safety and efficacy sections or in a new section preceding the efficacy and safety results sections. If particular types of information or topics are not addressed in ICH E3 or if their location is not specified, this information or topic should be placed in the section that is most relevant. For example, pharmacokinetic or quality of life results could be placed in appropriately identified subsections of the efficacy and safety results sections, or they could be placed in new, appropriately identified results sections. If a report does not address all the aspects of ICH E3 that are relevant for a given study, this should be clearly indicated and the rationale for doing so should be provided — for example, if there is no presentation of efficacy for an efficacy study. A rationale is not necessary if sections presented in ICH E3 are reordered, renamed, or deleted (if warranted by the study design) or if new sections are added. It should be noted that ICH E3 was developed for submission of adequate and wellcontrolled clinical effectiveness studies. Nevertheless, the basic principles described can be applied to other kinds of trials, such as clinical pharmacology studies and open-label safety studies, recognizing that not all sections or data presentations may be appropriate or important for these other types of trials. Sponsors are encouraged to adapt the recommendations in the guidance as appropriate (e.g., by deleting sections that are not relevant or adding important sections that are not mentioned in the guidance).
