Some in the pharmaceutical industry have expressed concern that the ICH E3 Guidance, Structure and Content of Clinical Study Reports (hereafter, E3), is intended as a requirement, i.e., a template that must be followed. The fact that the ICH M4 Guidelines for the CTD refer to specific structural elements described in E3 (e.g., Clinical Study Report [CSR] section headings) may have contributed to this interpretation. Interpretation of E3 as a rigid template can result in presentation of redundant and suboptimal information in CSRs. This is a particular problem when E3 is used for studies for which it was not designed (e.g., pharmacokinetic studies or studies with health economic or quality of life outcomes). Can ICH reaffirm that E3 is a Guideline and not a required template and that E3 may be adapted to report studies that fall outside the original scope of E3?

Yes. ICH E3 is a Guideline, not a set of rigid requirements or a template,
and flexibility is inherent in its use. “The Guideline 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 Guideline that lead to
better display and communication of information are encouraged.
The introduction to E3 (page 2) clearly indicates that E3 is to be
interpreted as a Guideline, 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.
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 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 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
E3 are re-ordered, renamed, or deleted (if warranted by the study design)
or if new sections are added.
It should be noted that E3 was developed for submission of adequate and
well-controlled 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 needed
for these other types of trials. Sponsors are encouraged to adapt the
recommendations in the Guideline as needed (e.g., by deleting sections
that are not relevant or adding needed sections that are not mentioned in
the Guideline).