Between-patient design

This design is what we refer to as a between-patient design. The basis of the treatment comparison is the comparison between two independent groups of patients. 

More generally the test statistic is constructed as the signal/noise (signal-to-noise) ratio or something akin to this. We will develop this methodology in relation the comparison of two independent means for a between-patient design. The resulting test is known as the unpaired t-test or the two-sample t-test. 

Comments as above for the between-patient designs apply also for the within-patient designs and in many cases the best approach will be to focus on a sequence of pairwise comparisons using the paired t-test. 

To illustrate the use of the formula suppose we are designing a trial to compare treatments for the reduction of blood pressure. We determine that a clinically relevant difference is 5 mmHg and that the between-patient standard deviation 0 is 10 mmHg. At)q)e-1 error is set at 0.05 and the type-11 error at 0.20. Then the required sample size, per group, is... 

The hepatitis C virus can be transmitted parenterally or sporadically. Risk groups with a high prevalence rate are haemophiliac patients (70-90%), i.v. drug addicts (50-90%), posttransfusion patients (60-80%), dialysis patients (5-30%) and liver transplant recipients. In 40-50% of patients with a positive anti-HCV test, the transmission route is still unknown. These cases are designated community-acquired or sporadic hepatitis C. The cause is rooted in poor hygienic conditions and close physical contact. Ill, 211, 334) Fundamentally, the possibility of infection depends on the virus titre in the source person - it is considerably lower than with HBV infection. Nosocomial infection between patients has also been observed. (281, 329, 390)... 

This test has very low power, however, for three reasons. (1) It is a between-patient test for a trial which has been designed to use within-patient differences to detect treatment effects. (2) The carry-over effect where it occurs is likely to be somewhat smaller than the pure effect of treatment. (3) The carry-over is in any case only manifested in the second period. Therefore, although it is necessary to use the totals to compare sequences to account for other effects that might bias the test of carry-over, the direct information for carry-over comes only from the second period and the effect of this is diluted. In short, although a test of carry-over is available it is too weak to be of much use. 

Thus, there is a point at issue here between those who believe that the problem of carry-over is potentially so devastating as to preclude within-patient studies and those who think that the predictive power of random-effect models in conjunction with appropriate within-patient designs is so great that the opportunity to conduct them must not be passed up. 

Contrary to these findings, reports from Asia indicate that 2-PAM treatment was not sufficiently effective in their patients. However, in their studies 2-PAM was not used as recommended by the WHO (de Silva et al., 1992 Singh et al., 1995 Johnson et al., 1996 Cherian et al., 1997, 2005). In addition, these studies were apparently poorly designed due to suboptimal dose, short duration of treatment, long delay between patient exposure, and... 

There are also differing standards between the markets in each of these countries. For instance, the telecom market has vastly different safety requirements than the patient-contact medical market. So, it is important to determine the target market early in the product design process. These market differences will also be included in the lEC standards harmonizing efforts. 

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