Clinical Overview

Safety - M4S(R2) Module 4 Non-clinical + Module 2 Non-Clinical Overview and Summary... 

Figure 6.6 Structure of the Non-clinical and Clinical Overview and Summary sections.

Hildreth, C. Saunders, O. (1991). Hypertension in Blacks clinical overview. Cardiovascular Clin., 21, 85-96. 

Vanhoefer U, Harstrick A, Achter-rath W et al. Irinotecan in the treatment of colorectal cancer clinical overview. J Clin Oncol 2001 19 1501-1518. 

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. 

In all cases, an Expert Report (or its CTD equivalent, the Clinical Overview), which is a critical analysis of the proposed availability of the product without a medical prescription with the dose and indications as stated in the application, must be provided. The expert is expected to take a clear position, defend the proposal in light of current scientific knowledge, and demonstrate why none of the criteria that determine classification for supply subject to a medical prescription applies to the product. 

Module 2 Common technical document summaries Overall common technical document table of contents Introduction Quahty overall summary Non-chnical overview Clinical overview Non-chnical summary Pharmacology Written summary Tabulated summary Pharmacokinetics Written summary Tabulated summary Toxicology... 

Wallace, S.J. (1994) Lamotrigine—a clinical overview. Seizure 3 (Suppl A) 47-51. 

Zisook S A clinical overview of monoamine oxidase inhibitors. Psychoso-matics 26 240-246, 1985... 

Rickels K, Schweizer E. Clinical overview of serotonin reuptake inhibitors. J din Psychiatry 1990 51[Suppl 12B] 9-12. 

Nosadini, R., Avogaro, A., Doria, A., Fioretto, P., Trevisan, R., Morocutti, A. (1989) Ketone body metabolism a physiological and clinical overview. Diabetes Metab. Rev. 5, 299-319. 

Musch B, Maillard F (1990) Zopiclone, the third generation hypnotic a clinical overview. Int Clin Psychopharmacol 5 (Suppl 2) 147-158... 

McMahon, T. C. (1986). A clinical overview of syndromes following withdrawal from antidepressants. Hospital and Community Psychiatry, 37, 883-884. 

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. 

Weger, N.P. (1983). Treatment of cyanide poisoning with 4-dimethylaminophenol (DMAP) - experimental and clinical overview. Fundam. Appl. Toxicol. 3 387-96. 

Maeda H, Sawa T, Konno T (2001) Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS. J Control Release 74 47-61... 

Modules II-V and an introductory document. The summaries cover manufacturing and quality control, nonclinical information (including toxicology) and a clinical overview (comparable to the expert report in previous forms of European submissions). 

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. 

When the new ICH Common Technical Document is fully adopted, the pharmaceutical physician may be called upon to write an expert report or a clinical overview. It is essential that whoever writes the report or overview should have a good understanding of the trial. Inaccuracies are too frequent. The report is a comprehensive and critical review of the data submitted in the license application and should not be more than 25 pages long (30 pages in the case of the clinical overview). The object of the report is to facilitate the review by the assessor and it should address the properties of safety and efficacy of the study drug, with cross-reference to... 

CTD Introduction Quality Overall Summary Nonclinical Overview Clinical Overview... 

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. 

Module 2 - Summaries in addition to a table of contents and a one-page introduction, this module contains the Quality Overall Summary, the Non-clinical Overview, and the Clinical Overview these are followed by the Non-clinical Written Summaries, the Non-clinical Tabulated Summaries, and the Clinical Summary separate documents (M4Q, M4S, and M4E) give guidance on the format and content of the summaries)... 

French, J.A. (2007) Refractory epilepsy clinical overview. Epilepsia, 48 (Suppl 1), 3-7. 

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