Integrated Summary of Efficacy

An applicant may provide an overall summary of data from controlled studies. This section is optional and many firms do not include it because the results of the studies are presented in the integrated summaries of efficacy and safety, which will be discussed later in this chapter. The Guidelines for the Clinical and Statistical Sections of a New Drug Application also address the format and content of an integrated clinical/statistical report for a clinical study this too will be discussed later. 

An analysis of responses in subsets of the overall population is required. The extent of this part of the integrated summary of efficacy will depend to a large extent on the drug and its intended patient population. Subsets of interest may include sex, race, age, disease severity, concomitant illness, concomitant drugs, smoking and alcoholism, and prior therapy. 

Objective 4 is to confirm drug effectiveness in large-scale clinical trials. The results of these trials are summarized in the Integrated Summary of Efficacy (ISE) portion of the NDA/BLA submission and play an important role in determining appropriate therapeutic indications, dose regimens, and benefit/risk ratios for various patient populations. 

The Commission, in conjunction with the Notice to Applicants Working Party, completed its work on the incorporation of the ICH Common Technical Document (CTD) into a revision of Volume 2B of the Notice to Applicants. A schematic representation of the correspondence between the five modules of the CTD and the four parts of the European registration dossier has also been prepared in order to facilitate the transition from the old application format to the new one. The non-clinical and clinical overviews and summaries are equivalent to the present expert report described above. The clinical summary may replace the Integrated Summary of Efficacy and Integrated Summary of Safety Required by the FDA, and the Clinical Overview and Clinical Summary have been designed to replace the Japanese GAIYO. 

ISS) and the integrated summary of efficacy (ISE). These analyses must be planned for just as if the combined database represented data from a new study. It is recommended that plans for meta-ana-lyses will be made at the time the individual studies are planned. This is not always possible, but it is the best way to ensure that the meta-database used for the analysis is coherent. For example, if the adverse events information is collected in two studies using different data collection forms, the combination of the individual databases may be difficult and some information may be lost. 

---