Module 5 Clinical Study Reports

The following points are worthy of note in terms of the placement of data. In the case of studies with multiple objectives, reports should be placed in the section corresponding to their primary purpose. Reports of laboratory studies conducted with human materials to investigate pharmacokinetic effects should be placed in Section 5.3.2 of the clinical module, as opposed to the non-clinical module. A US submission requires that the individual case report forms of all trial subjects that died or were dropped from a study due to adverse events are included in Section 5.3.7. 

3 Prenatal and postnatal development, including maternal function 

4 Studies in which the offspring (juvenile animals) are dosed and/or further evaluated. 

4 Reports of Bioanalytical and Analytical Methods for Human Studies 

2 Reports of Studies Pertinent to Pharmacokinetics using Human Biomaterials 

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Literature references Module 5 Clinical Study Reports... 

Module 5 Clinical study reports. This covers human study reports and related information presented in the order described in guideline M4F. 

Module 4 - Non-clinical Study Reports Module 5 - Clinical Study Reports... 

The CTDs were implemented in July 2003. They are format-based documents for submission to the regulatory authorities the country-specific process of review, for example, via the IND and NDA of the United States or the Centralized Procedure of the EMEA, is not affected. The harmonized CTDs help to reduce cost and accelerate approval time. Figure 7.1 shows the CTD structure five modules with Module 1 for regional administrative information specihc to each country. Module 2 on summary of quality, nonclinical and clinical. Module 3 on quality. Module 4 on nonclinical study reports, and Module 5 on clinical study reports. 

CTD consists of four modules, preceded by a Module 1 that is region-specific and includes administrative and prescribing information. Module 2 comprises of CTD summaries and overviews of the quality, non-clinical and clinical data. Module 3 contains data on quality. Module 4 consists of the non-clinical study reports and Module 5 comprises the clinical study reports. There are guidelines on the details to be included in each module and these are summarised in Box 17.2. The non-clinical and clinical overviews and summaries are equivalent to the previous Expert Reports submitted under sections IC2 and IC3 respectively of part I, data. 

Module 4 Non-clinical study reports Table of contents Study reports Literature references... 

M4 is another very important multidisciplinary guideline, which combines information for the 3 disciplines within the ICH Process for Quality, Safety and Efficacy. The following section focuses predominantly on the preclinical safety issues. The total document is divided into 5 modules Module 1 contains regional specific aspects, it provides for the European Union e.g. the European Community specific data. This module therefore is not harmonized but region-specific. Module 2 provides the Summaries for Quality, for Safety and Efficacy. The quality part uses as a headline Quality Overall Summary , for safety and efficacy the terms Non-Clinical or Clinical Overview . The different names signal that the quality part is a clear summary, while the non-clinical and clinical part should be critical evaluations. Module 3 provides chemical, pharmaceutical and biological information. Module 4 contains the non-clinical reports and Module 5 provides clinical study reports. 

Module V then contains the clinical study reports - again starting with a table of content for the module. A tabular summary of the studies is useful when inserted before the study reports themselves. 

Update or Addendum to quality summaries, non-clinical overviews and clinical overviews (the former expert reports ) as may be relevant. When nonclinical or clinical study reports are submitted, their relevant summaries should also be included in Module II. 

The last section of a Clinical Summary is recommended to contain a table entitled Listing of Clinical Studies (ETA). This table is also to be included in Module 5. Following the table are to be individual clinical study synopses organized in the same sequence as the clinical study reports in Module 5. The ICH E3 guideline on Structure and Content of Clinical Study Reports provides an example of a format for a clinical study report synopsis, which can be used for marketing applications in all ICH regions. 

Table 5 Order of Presentation for Clinical Study Reports and Related Information (Module 5)...

A wide variety of clinical studies report beneficial effects from macrolide therapy in many inflammatory diseases and notably lung diseases. In many instances, these effects are obtained in the absence of clear infections. This had led to considerable debate as to whether the main mode of action in these settings is one of anti-inflammatory activity or whether subtle modulation of bacterial vigour leads to greater benefits than might be expected. Effects on bacteria may also include interference in quorum sensing or biofilm formation that may not be associated with effects on growth rate of planktonic forms in culture. 

This module should contain reports of all the clinical studies and other related data that were conducted to demonstrate the safety and efficacy of the drug in human subjects. The standard headings used to present this information are shown in Figure 6.5. An example of headings for a tabulated listing of clinical studies is shown in Table 6.4. 

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