Clinical Trial Design

There are two main types of clinical trial design, parallel and cross-over. In a parallel study, subjects are assigned to one of two or more treatments, e.g. active and placebo, and proceed through the trial concurrently. In a cross-over design, subjects act as their own controls, undergoing two or more treatments in sequence (see Fig. 12.1). 

Further information and advice related to the use of the clinical trial design can be found in a variety of sources including textbooks, manuscripts, organizations and Internet sites. In addition to the chapter reference list which cites helpful sources of information related to clinical trial protocol development, design and analysis, the following sources are also recommended. 

Once absorbed, ezetimibe undergoes extensive glucuronida-tion in the intestinal wall to the active metabolite (ezetimibe glucuronide). Ezetimibe and the active metabolite are entero-hepatically recirculated back to the site of action, which limits systemic exposure and may explain the low incidence of adverse effects (Table 9-9). Ezetimibe alone or with a statin is contraindicated in patients with active liver disease or unexplained persistent elevations in LFTs. Currently, clinical trials designed to determine ezetimibe s effects on CHD morbidity and mortality have not been completed. The time until maximum effect on lipids for ezetemibe is generally 2 weeks. 

Crossover design A clinical trial design in which patients receive, in sequence, the treatment (or the control), and then after a specified time, receive the opposite arm of the trial. This allows patients to serve as their own controls. Randomization should be... 

Table 4.5 Some clinical trial design types. Additional information may be sourced from appropriate references provided in the Further reading section...

Division of Clinical Trial Design Analysis Karen D. Weiss, M.D. 

Division of Clinical Trial Design and Analysis Preclinical pharmacology and toxicology Clinical trial design, safety and efficacy 20% of CBER clinical protocols are now for gene therapy. 

As presented in Section 20.5, a number of factors in clinical trial design make the identification and evaluation of adverse effects a challenge. Actions in addressing these challenges include the following. 

On the Distant Horizon — Challenges for Clinical Trial Design. 453... 

New Agents with More Unique Cytostatic Mechanisms of Action and Their Unique Clinical Trial Designs... 

David Essayan Food and Drug Administration, Center for Biologies Evaluation and Research, Office of Therapeutics, Division of Clinical Trial Design and Analysis, Rockville, Maryland, U.S. 

The impact of these considerations on study subject selection, sample size and endpoint measures will need to figure in future clinical trial designs. 

There is much controversy over the use of open or open-label studies. It is a golden rule of clinical trial design that, wherever practicable and possible, open studies should not be conducted, but there are circumstances when they can or must be used (see Box 6.2). 

Many of the important statistical aspects of clinical trials design are dealt with in detail in Chapter 6 of this volume (Nigel Baber and John Sweatman) and so here only specific statistical aspects are discussed. 

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