Clinical trials trial design

As defined by ICH and GCP guidelines, a subinveshgator is any individual member of the clinical trial team designated and directly supervised by the PI to perform trial-related procedures or make trial-related decisions (Sechon 1.56, p. 13). ° Examples of subinvestigators include other physicians, pharmacists, pharmacologists, nurses, and study coordinators. 

The National Institute for the Control of Pharmaceutical Biological Products (NICPBP) performs tests on the drug samples submitted. Based on the test results and the report from the CDE, the DDR approves the conduct of clinical trials at designated hospitals in China (Fig. 8.13). 

A good clinical trial is designed to take account of the variability in response (either efficacy or adverse event) that is expected when a new active drug is tested. This response depends on an individual s genetic make-up, and on a number of environmental factors, such as disease state, other drugs and age. The size of the trial and the selection of study subjects are carefully determined to reduce the variability in response to a minimum (i.e. to maximise the sensitivity of the trial) so that the trial endpoints can be determined with as much certainty as possible. 

More specifically in the context of clinical trials, proper design confers many advantages, including the following ... 

Good Clinical Practice (GCP) The standard by which clinical trials are designed, implemented and reported so that there is public assurance that the data are credible, and that the rights, integrity, and confidentiality of subjects are protected. [Defined for this book.]... 

The Controlled Clinical Trial basic design elements... 

THE CONTROLLED CLINICAL TRIAL BASIC DESIGN ELEMENTS... 

The previous sections have described how a clinical trial is designed, the documentation that must be prepared, and the preparation, documentation and dispatch of clinical trial material. None of these areas should be carried out in isolation and need to be addressed long before the first study subject is recruited. The pharmaceutical physician cannot be responsible for all these tasks unless he or she is carrying out independent research. Even then, he or she should seek expert help in the design of the study in relation to the statistical analysis and how the data will be collected and entered onto a database. 

Clinical development programs consist of a variety of preapproval clinical trials, all designed for a specific purpose of revealing particular information concerning the investigational drug s safety and efficacy. 

Define the following aspects of clinical trial study design ... 

Synthetic surfactant (Exosurf) was studied in a placebo-controlled trial of patients with ARDS. While this therapy also failed to show benefits, the drug was aerosolized over 5 days to administer 240 mL Exosurf. Since aerosolized surfactant is poorly delivered and was shown recently to be ineffective in neonates with RDS, this trial cannot be considered of value in gauging the efficacy of surfactant for ARDS. Also, natural surfactants that also have surfactant proteins may be a better choice. Phase 111 studies using a recombinant SP-C-based surfactant showed reduced mortality for the subgroup of patients with ARDS secondary to direct insults, although no benefit was seen for the total study population. It is important to consider etiologies for ARDS when future clinical trials are designed. 

Another possibility is that the later clinical trials were designed to support applications for indications other than those contained in the initial NDA. Even though the firm would file data on the efficacy of the drug for the additional indications in subsequent NDAs, the FDA would still expect the sponsor to file safety data from all completed trials for consideration of the first NDA. This explanation is consistent with the observation that in two of the therapeutic classes examined, the average number of indications contained in the initial NDA declined over time. In an effort to market the drug as early as possible, sponsors may be reducing the number of uses for which it seeks initial FDA approval. 

Phase II clinical trials are designed to evaluate the producfs efficacy and side-effect profile. About 100-300 patients are involved. Data obtained are used to characterize the dose-response relationship. The costs involved are about 10-100 million Euro over 1- to 2-year period. The success rate is about 40%. Studies performed may be characterized by a single or multicenter study, single- or double-blinded with a control group and randomization of the patients. Amongst the most common reasons for failure at this phase are poorly designed studies and ineffective or unsafe products. 

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