Phase 11 trials, drug development

Non-inferiority trials are more common than equivalence trials in Phase III drug development. In these, the objective is to show that a new treatment is no less effective than existing treatment. It... 

Phase III studies represent the confirmatory phase of drug development, which takes several years and usually involves several thousand patients at multiple trial centers. Large patient numbers are required in these trials to provide convincing documentation of clinical efficacy and safety, a more complete adverse event profile and covariates and estimates of variability in dose response relationship due to individual differences in pharmacokinetics and pharmacodynamics. They are aimed at definitively determining a drug s effectiveness and side-effect profile. Most of these studies are double-blind and placebo-controlled, sometimes with the option of open-label long-term extensions. 

This is the classic randomised controlled trial (RCT), the most secure method for drawing a causal inference about the effects of treatments. Randomisation attempts to control biases of various kinds when assessing the effects of treatments. RCTs are employed at all phases of drug development and in the various types and designs of trials discussed below. 

Dose-response trials. Response in relation to the dose of a new investigational drug may be explored in all phases of drug development. Dose-response trials serve a number of objectives, of which the following are of particular importance. 

Hughes, D.A. Walley, T. Economic evaluations during early (phase II) drug development a role for clinical trial simulations Pharmacogenomics 2001, 19 (11), 1069-... 

There are several common classes of study design. These classes apply to almost all phases of drug development. No list of trial designs can be... 

Non-inferiority trials are more common than equivalence trials in Phase III drug development. In these, the objective is to show that a new treatment is no less effective than existing treatment. It may be more effective or equivalent, but using the confidence interval approach, the only interest is a possible difference in one direction. Hence the 95% confidence interval should be entirely to the right of the point estimate for superiority and other trials (see Figure 6.2). 

Finally, the appeal of sourcing in China is based on China s low cost stmcture for all phases of drug development. The costs of conducting clinical trials in China is approximately 20 to 25% of those in the United States. A full-time equivalent (FTE) in China costs about US 40,000 to US 100,000 per year in the Shanghai area and even less in inland regions such as Chengdu. In the United States, an FTE costs upward of US 200,000 to US 250,000 per year. In addition to low overhead costs, the hourly wages in China are about 25% those of Western countries. 

Sphker, B. Phases of clinical trials and phases of drug development, Drug News Perspectives 9(10), 601-606 (1996). 

Many cross-over trials are carried out in early phases of drug development or in order to investigate rather specialist questions such as, the hioequivalence of two formulations. (This particular topic is covered in detail in Chapter 22.). Most such studies are singledose studies. The subject is given a single dose of a treatment in a given period and then the pharmacokinetic or pharmacodynamic effects of the treatment are studied... 

There are several common classes of study design. These classes apply to almost all phases of drug development. No list of trial designs can be exhaustive, because almost all clinical trials are different. What follows is an attempt to briefly review the classes of clinical trial design that will encompass a large majority of studies, and to comment on their economy and end-point possibilities. 

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