Clinical studies reports

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

E3 Structure and Content of Clinical Study Reports Dose-Response Studies... 

Non-Clinical Study Reports Toxicological and Pharmacological Tests 111... 

The E3 describes in detail what reporting goes into a clinical study report for an FDA submission. This guidance is of major importance, as you are often required to generate tables, figures, case report tabulations, and perhaps clinical narrative support for the clinical study report. 

In guidance document ICH E3, Structure and Content of Clinical Study Reports, the FDA defines treatment-emergent signs and symptoms (TESS) as events not seen at baseline and events that worsened even if present at baseline. As simple as that may sound, it can sometimes be quite difficult to program. The important data variables that come into play are dosing record dates and times, adverse event start and stop times, and adverse event severity. All of these data variables need to be completed accurately for TESS to be calculated properly. 

The study termination form data may be used for efficacy or safety analysis purposes. With regard to safety, if patients discontinue a study medication earlier than patients on standard therapy or placebo, then that is important to know. For efficacy analyses, patients who withdraw due to a lack of efficacy or adverse event may be precluded from being considered a treatment responder or success. Also, often the study termination date is used as a censor date in time-to-event analyses for therapy efficacy. Study termination forms play a key role in patient disposition summaries found at the start of a clinical study report. From a CDISC perspective, the study termination form is a finding. 

International Conference on Harmonization. Guideline for Industry—Structure and Content of Clinical Study Reports, ICH E3, 1995. http //www.ich.org/LOB/media/ MEDIA479.pdf [accessed October 10, 2007]. 

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. 

Efficacy Nine topic headings—Clinical Safety, Clinical Study Reports, Dose-Response Studies, Ethnic Factors, GCP, Clinical Trials, Clinical Evaluation by Therapeutic Category, Clinical Evaluation, Pharmacogenomics total of 18 guidelines... 

International Conference on Harmonisation of Technical Requirements of Pharmaceuticals for Human Use (ICH). Topic E3 Note for Guidance on Structure and Content of Clinical Study Reports, CPMP/ICH/137/95. London European Agency for the Evaluation of Medicinal Products, 1996. 

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. 

Literature references Module 5 Clinical Study Reports... 

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

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

ICH E3(1995) Structure and Content of Clinical Study Reports sets down the structure, down to the numbering of the sections and precisely what goes in each of those sections, required within the regulatory setting for reporting each study. Medical writers will work with statisticians to put these reports together. 

A revised sample size may then be calculated using suitably modified assumptions, and should be justified and documented in a protocol amendment and in the clinical study report... The potential need for re-estimation of the sample size should be envisaged in the protocol whenever possible. ... 

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