Clinical trial tables

Systematic screening experiments have identified more than 100 synthetic compounds with potent antiangiogenic activity. The mode of action for most of these molecules is not well understood, but some of the 40 compounds are well advanced in clinical trials (Table 3). The first substance to have entered clinical trials was the Fumagillin-derivative AGM 1470. Fumagillin is an antibiotic which inhibits bFGF- and PDGF-induced endothelial cell proliferation. The mechanism of action of AGM 1470 is poorly understood, but it was shown that it binds and inhibits the metalloprotease methionine aminopeptidase (MetAp-2). 

General Approach to Creating Tables 126 A Typical Clinical Trial Table 127... 

This chapter first explores the general approach to creating any statistical table or listing. Then it examines PROC REPORT and PROC TABULATE as possible stand-alone methods of clinical trial reporting. Next, examples of several common clinical trial tables are presented. Finally, issues concerning the appearance of the output are discussed. 

Note that for generating tables there are single SAS procedures such as PROC TABULATE and PROC REPORT that can perform all of the preceding four steps. We will examine PROC TABULATE and PROC REPORT as possible reporting methods after you see what a typical clinical trial table looks like. 

Clinical trial tables have certain common features. A sample annotated demographics table follows, with annotated descriptions of the key features. 

Using PROC TABULATE to Create Clinical Trial Tables... 

PROC TABULATE is an excellent tool for producing quick descriptive statistics on data, but it does not meet the typical needs of generating clinical trial tables, for several reasons ... 

PROC REPORT as a stand-alone tool is not very useful for creating clinical trial tables,... 

The previous sections show you how to extract / -values for a commonly used set of statistical tests. This section describes a general step-by-step approach for getting your statistics from a SAS procedure into data sets for clinical trial table or graph reporting. Here are the steps to follow ... 

An investigational new drug is a new chemical-based, biologic or biopharmaceutical substance for which the FDA has given approval to undergo clinical trials. An IND application should contain information detailing preclinical findings, method of product manufacture and proposed protocol for initial clinical trials (Table 4.9). 

The first IL to be approved for medical use was IL-2, approved in 1992 by the FDA for the treatment of renal cell carcinoma. Several additional IL preparations are currently in clinical trials (Table 5.2). 

As haemopoietic growth factors serve to stimulate the production of mature blood cells, their clinical application in diseases characterized by sub-optimal production of specific blood cell types was obvious. Several CSF preparations have gained regulatory approval, or are currently being assessed in clinical trials (Table 6.4). G-CSF and GM-CSF have proved useful in the treatment of neutropenia. All three CSF types are (or are likely to be) useful in the treatment of infectious diseases, some forms of cancer and the management of bone marrow transplants (Table 6.4), as they stimulate the differentiation/activation of white blood cell types most affected by such conditions. 

The ability of such factors to promote accelerated cellular growth and division has predictably attracted the attention of the pharmaceutical industry. The clinical potential of a range of such factors, e.g. to accelerate the wound-healing process, is currently being assessed in various clinical trials (Table 7.2). 

The Indian regulatory system requires submission of reproductive toxicity study data in animals in support of Phase II and Phase III clinical trials. Table I provides all preclinical data that are required for the various phases of clinical studies. 

Uncontrolled clinical trials Table of all studies grouped by study type and reports of individual studies in each group. Other studies and information Reports of controlled or uncontrolled study of uses not claimed in the application, reports of commercial marketing experience. 

The stimulant drugs, including all methylphenidate and amphetamine products, produce a wide array of adverse effects on the brain and mind as well as the overall body. Strattera, marketed by Eli Lilly as a nonstimulant, shares most of these adverse effects. Table 11.1 summarizes the adverse drug reaction data from eight controlled clinic trials. Table 11.2... 

At the end of 2008, there were five NP-derived compounds in the New Drug Application (NDA) development phase in the USA and/or Market Authorisation Application (MAA) in Europe and thirty-one NP-derived compounds undergoing Phase III clinical trials (Table 11.2). Details of late stage clinical trials, mechanism of action and derivation of each compound are described in this section. 

The majority of gene therapy clinical trials are for cancer, with trials ongoing for almost all types of cancers. In addition, gene therapy for cancer is closest to the clinic, with both p53 and HSV-TK gene therapy in phase III clinical trials (Tables 4 and 5). 

Trabectedin enters phase I clinical trial (table 1) due to its efficacy and therapeutic outcome in preclinical studies against several types of cancers. According to the obtained results, hepatotoxicity (elevation of alkaline phosphatase in half of patient receiving trabectedin treatment) and non-cumulative hematological toxicity were the most commonly reported adverse effeets [29]. However, vomiting, fatigue, asthenia, and reversible transaminitis were other dose-limiting toxicity of treatment in phase I (0.75 mg/m i.v. on day 1 every 3 weeks) [30, 31]. 

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