The US Food and Drug Administration (FDA) has released a new final guidance for industry explaining the E3 Structure and Content of Clinical Study Reports guideline, part of ongoing efforts by regulators to clarify some of the more common questions and answers about the longstanding guideline.
The E3 guideline was approved by the International Conference on Harmonisation (ICH) in 1995, and adopted by FDA on 17 July 1996. It describes how sponsors can compile a single core clinical study report acceptable by FDA, the European Medicines Agency (EMA) and Japan's Ministry of Health, Labour and Welfare (MHLW)-the three main ICH regions.
The document is in many ways the backbone of the current Common Technical Document (CTD), which is composed on modules and allows application sponsors to organize their clinical data into a single integrated report.
Prior to the guideline (and the subsequent ICH M4 document that established the CTD), companies faced the prospect of having to submit an entirely different document to meet the requirements of each regulatory authority, requiring huge amounts of time to accomplish with little additional benefit.
But even as the guideline's basics have long been understood, numerous-and apparently oft-cited-issues have been raised with ICH, causing it to release its new guidance. The new document answers seven questions often posed by industry.
Questions and Answers
Of particular concern to industry is the perception by many that E3 is at this point something more than a guideline, but rather a required template. "The fact that the ICH M4 guidance for the Common Technical Document (CTD) refers to specific structural elements described in ICH E3 (e.g., Clinical Study Report (CSR) section headings) may have contributed to this interpretation," ICH explained. However widespread the misperception, ICH explained that the E3 guideline is just that-a guide, not a requirement.
Application sponsors are therefore able to exercise limited amounts of flexibility within the document, though the acceptance of those forms is subject to the requirements of each individual regulatory authority, it explained.
Other points touched upon in the guidance document pertain to more niche matters of interest. The E3 guidance, for example, directs sponsors to write a maximum of three pages summarizing the report, while a subsequent M4E guidance indicates that sponsors may author as many as 10 pages summarizing the report. In this case, the M4E guideline's instruction that summaries may exceed three pages in length supersedes the E3 guideline, ICH said.
Yet another section points out that reports of deaths in a clinical trial could potentially be listed in two sections described by the E3 guideline: sections 220.127.116.11 ("Deaths") and 18.104.22.168 ("Other Serious Adverse Events"). That information should be captured in the 22.214.171.124 listing, but listings in the latter are optional and acceptable as well, ICH wrote.
The full guidance is available on FDA's website here.